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LONG–TERM FOOD RESTRICTION PREVENTS THE AGE-RELATED CHANGES OF THE CONTENT OF BIOLOGYCALLY ACTIVE SPHINGO- AND GLYCEROLIPIDS СONTENS IN THE RAT TISSUES.

Babenko NA, Storozhenko GV.

Fiziol Zh. 2016;62(2):103-9.

PMID: 29537233

Abstract

Age peculiarities of the calorie-restricted diet effects on the contents biologically active sphingo- and glycerolipids were studied in the heart, liver and brain of 3- and 24-month-old rats. Rats were either kept on the ad libitum diet or on a calorie restricted diet (70-80% reduction in total calories) without reduction in essential nutrients. It has been determined that calorie restricted diet decreased the ceramide, sphingomyelin, cardiolipin and phosphatidic acid levels in the all investigated tissues of the rats. At the same time, calorie restriction diet prevented the age-induced ceramide and phosphatidic acid accumulation, ceramide/sphingomyelin ratio elevation, and sphingomyelin and cardiolipin content decrease in the tissues of 24-month-old rats. In addition, tissue specificity of calorierestricted diet effects has been determined. The Elevated levels of cardiolipin and phosphatidic acid were determined in the heart and liver of 24 months-old rats under calorie-restricted diet, in comparison to control animals, whereas in the brain the caloric restriction diet had the opposite effects. These results suggest that calorie-restricted diet may prevent the development of age-associated pathologies due to the modulation of biologically active lipid turnover in the old tissues.

 

Effect of short term quercetin, caloric restriction and combined treatment on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged rat brain.

Alugoju P, Swamy VK, Periyasamy L.

CNS Neurol Disord Drug Targets. 2018 Mar 14. doi: 10.2174/1871527317666180314120507. [Epub ahead of print]

PMID: 29542424

Abstract

Aging is characterized by gradual accumulation of macromolecular damage leading to progressive loss of physiological function and increased susceptibility to diverse diseases. Effective anti-aging strategies involving caloric restriction or antioxidant supplementation are receiving growing attention to attenuate macromolecular damage in age associated pathology. In the present study, we for the first time investigated the effect of quercetin, caloric restriction and combined treatment (caloric restriction with quercetin) on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged male wistar rat brain. 21 months aged rats were divided into four groups (n=6-8) such as group 1-fed ad libitum (AL); group 2-quercetin supplementation of 50 mg/kg b.w/day for 45 days fed ad libitum (QUER); group 3: caloric restricted (CR) (fed 40% reduced AL for 45 days); group 4-fed 40% CR and 50 mg/kg b.w/day QUER for 45 days (CR + QUER). Group 5-three month age old rats served as young control (YOUNG). Our results demonstrate that combined treatment of caloric restriction and quercetin significantly improved the age associated decline in the activities of endogenous antioxidant enzymes [such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and glutathione (GSH) content and attenuated elevated levels of protein carbonyl content (PCC), lipid peroxidation, lipofuscin, reactive oxygen species (ROS), and nitric oxide (NO). Furthermore, it is also observed that combined treatment ameliorated age associated alterations in acetylcholine esterase (AChE) and adenosine triphosphatases (ATPases) such as Na+/K+-ATPase and Ca+2-ATPase (but not Mg+2-ATPase) enzyme activities. Finally, we conclude that combined Mg+treatment of caloric restriction and quercetin (but not either treatment alone) in late life is an effective anti-aging therapy to counteract the age related accumulation of oxidative macromolecular damage.

KEYWORDS:

acetylcholinesterase; and ATPases; anti-aging; oxidative stress; quercetin

 

Exercise and weight loss effects on cardiovascular risk factors in overweight men.

Rosenkilde M, Rygaard L, Nordby P, Nielsen LB, Stallknecht B.

J Appl Physiol (1985). 2018 Mar 15. doi: 10.1152/japplphysiol.01092.2017. [Epub ahead of print]

PMID: 29543138

Abstract

Exercise training and weight loss both reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 weeks of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control ©. Equal energetic deficits (-600 kcal/day) were prescribed by exercise for T and caloric restriction for D. T-iD completed similar exercise but remained in energy balance due to the dietary replacement of calories expended during exercise. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B and A1, preβ-HDL, and susceptibility of LDL-C to oxidation were measured. Body weight was reduced similarly between T (-5.9{plus minus}0.7 kg) and D (-5.2{plus minus}0.8 kg) while T-iD (-1.0{plus minus}0.5 kg) and C (0.1{plus minus}0.6 kg) remained weight stable. Plasma TC, LDL-C, and apolipoprotein B were reduced in T compared to C (P<0.001 for both), but this was not observed for D (P>0.17). Changes in TC and LDL-C were associated with changes in body weight and body fat (P<0.01). In T-iD, increases in HDL-C and apolipoprotein A1 were observed (P<0.001). In conclusion, an exercise-induced decline in body weight reduces pro-atherogenic apoB-containing lipoproteins, whereas exercise compensated by energy intake increases the key component of reverse cholesterol transport, i.e. ApoA1-containing HDL-C.

KEYWORDS:

Physical activity; cardiovascular risk; cholesterol; diet; lipids

 

Acute food deprivation separates motor-activating from anxiolytic effects of caffeine in a rat open field test model.

Schulz D.

Behav Pharmacol. 2018 Mar 14. doi: 10.1097/FBP.0000000000000396. [Epub ahead of print]

PMID: 29543609

Abstract

Similar doses of caffeine have been shown to produce either anxiolytic or anxiogenic effects in rats. The reasons for these conflicting results are not known. We hypothesized that food deprivation stress interacts with the stimulant effects of caffeine to increase anxiety-like behavior. We tested 32 female Sprague Dawley rats in a dim open field for 10 min. Half of the animals were food deprived for 24 h and injected (intraperitoneal) with caffeine (30 mg/kg; n=7) or deionized water (n=8) 20 min before the open field test. The other half was nondeprived and injected with caffeine (30 mg/kg; n=8) or deionized water (n=9). Results showed that nondeprived rats injected with caffeine moved longer distances and at a greater speed in the periphery and moved longer distances and spent more time in the center than rats treated with vehicle, indicative of motor-activating and/or anxiolytic effects of caffeine. Rats that were food deprived and injected with caffeine moved longer distances in the center and tended to spend more time there, indicative of anxiolysis. We conclude that caffeine had two effects on behavior, motor activation and a reduction of anxiety, and that food deprivation separated these effects.

 

Effect of short term quercetin, caloric restriction and combined treatment on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged rat brain.

Alugoju P, Swamy VK, Periyasamy L.

CNS Neurol Disord Drug Targets. 2018 Mar 14. doi: 10.2174/1871527317666180314120507. [Epub ahead of print]

PMID: 29542424

Abstract

Aging is characterized by gradual accumulation of macromolecular damage leading to progressive loss of physiological function and increased susceptibility to diverse diseases. Effective anti-aging strategies involving caloric restriction or antioxidant supplementation are receiving growing attention to attenuate macromolecular damage in age associated pathology. In the present study, we for the first time investigated the effect of quercetin, caloric restriction and combined treatment (caloric restriction with quercetin) on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged male wistar rat brain. 21 months aged rats were divided into four groups (n=6-8) such as group 1-fed ad libitum (AL); group 2-quercetin supplementation of 50 mg/kg b.w/day for 45 days fed ad libitum (QUER); group 3: caloric restricted (CR) (fed 40% reduced AL for 45 days); group 4-fed 40% CR and 50 mg/kg b.w/day QUER for 45 days (CR + QUER). Group 5-three month age old rats served as young control (YOUNG). Our results demonstrate that combined treatment of caloric restriction and quercetin significantly improved the age associated decline in the activities of endogenous antioxidant enzymes [such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and glutathione (GSH) content and attenuated elevated levels of protein carbonyl content (PCC), lipid peroxidation, lipofuscin, reactive oxygen species (ROS), and nitric oxide (NO). Furthermore, it is also observed that combined treatment ameliorated age associated alterations in acetylcholine esterase (AChE) and adenosine triphosphatases (ATPases) such as Na+/K+-ATPase and Ca+2-ATPase (but not Mg+2-ATPase) enzyme activities. Finally, we conclude that combined Mg+treatment of caloric restriction and quercetin (but not either treatment alone) in late life is an effective anti-aging therapy to counteract the age related accumulation of oxidative macromolecular damage.

KEYWORDS:

acetylcholinesterase; and ATPases; anti-aging; oxidative stress; quercetin

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I did not post for a while because I drove a little over 3400 km to and from where my Mom lives, with an 11 day stay there, to get together with the family for Mom's 95th birthday.

 

Relationship of Physical Function to Single Muscle Fiber Contractility in Older Adults: Effects of Resistance Training with and without Caloric Restriction.

Wang ZM, Leng X, Messi ML, Choi SJ, Marsh AP, Nicklas B, Delbono O.

J Gerontol A Biol Sci Med Sci. 2018 Mar 13. doi: 10.1093/gerona/gly047. [Epub ahead of print]

PMID: 29546320

https://watermark.silverchair.com/gly047.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdUwggHRBgkqhkiG9w0BBwagggHCMIIBvgIBADCCAbcGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMWQGLfFaL-3rWjTnlAgEQgIIBiBNa61TlqMdhw1Ol7wh03EaPUq9g1sRFy9MUxaOJkjF0-cHI4HieTDo6eb-Hz8GQ2Kq7rOXwBg8qPkgwetqKt2gC4VLRH5e9-7Bv9UuZPwhtMtpF0Mvzbj4idSr791SucrYjd5QDpd7ur0dwLbK4FeOpKwXMJeC2XEiCPnlV2i8_NylZmZaJ1IYYr89GHeobVaGReHU0YWWZeV27iFd32HdZg6sjWnOCKWEAm7fJyC5kPGajUiuOHoFEvjeOXr9amO-E1hwe3A5F5fAvFk0FsZhhu1oAgOIdNagKeWzyuLAEUy2dtK-T12TiYkVaHg4OGJ6P8f0XApMgjE8IQSpC3uk3uzl14LvnHAY0tpbdh14xsMTfZ0pbKGvyDIunGENchxdyZgc0NbRif9IhG1rN6QfXMta8LuGW9wiobj9YYTkDVhxpHoMc7Qc5NEaZmmKQFQ72L6Ol5wAYZwnN_lmc4hd2kDDTMHw_Sn0o3YtKarpKYze42K1igAjz191Xwk_mPyeA4pa5R4aC

Abstract

BACKGROUND:

Previous studies support beneficial effects of both resistance exercise training (RT) and caloric restriction (CR) on skeletal muscle strength and physical performance. The goal of this study was to determine the effects of adding CR to RT on single-muscle fiber contractility responses to RT in older overweight and obese adults.

METHODS:

We analyzed contractile properties in 1,253 single myofiber from muscle biopsies of the vastus lateralis, as well as physical performance and thigh muscle volume, in 31 older (65-80 yrs), overweight or obese (body mass index= 27-35 kg/m2) men (n=19) and women (n=12) who were randomly assigned to a standardized, progressive RT intervention with CR (RT+CR; n=15) or without CR (RT; n=16) for 5 months.

RESULTS:

Both interventions evoked an increase in force normalized to CSA, in type-I and type-II fibers and knee extensor quality. However, these improvements were not different between intervention groups. In the RT group, changes in total thigh fat volume inversely correlated with changes in type-II fiber force (r = -0.691; p=0.019). Within the RT+CR group, changes in gait speed correlated positively with changes in type-I fiber CSA (r=0.561; p=0.030). In addition, increases in type-I normalized fiber force were related to decreases in thigh intermuscular fat volume (r= -0.539; p= 0.038).

CONCLUSION:

Single muscle fiber force and knee extensor quality improve with RT and RT+CR; however, CR does not enhance improvements in single muscle fiber contractility or whole muscle in response to RT in older overweight and obese men and women.

 

Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction.

Madreiter-Sokolowski CT, Sokolowski AA, Waldeck-Weiermair M, Malli R, Graier WF.

Genes (Basel). 2018 Mar 16;9(3). pii: E165. doi: 10.3390/genes9030165. Review.

PMID: 29547561 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867886/

Abstract

Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS). Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism's process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR) or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria's role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

KEYWORDS:

aging; aspirin; caloric restriction; caloric restriction mimetics; exercise; mitochondria; polyphenols

 

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine jejunal epithelium.

Keogh K, Waters SM, Cormican P, Kelly AK, Kenny DA.

PLos One. 2018 Mar 19;13(3):e0194445. doi: 10.1371/journal.pone.0194445. eCollection 2018.

PMID: 29554113 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858768/

Abstract

Compensatory growth (CG), an accelerated growth phenomenon which occurs following a period of dietary restriction is utilised worldwide in animal production systems as a management practise to lower feed costs. The objective of this study was to evaluate the contribution of jejunal epithelial to CG in cattle through transcriptional profiling following a period of dietary restriction as well as subsequent re-alimentation induced CG. Sixty Holstein Friesian bulls were separated into two groups; RES and ADLIB, with 30 animals in each. RES animals were offered a restricted diet for 125 days (Period 1) followed by ad libitum feeding for 55 days (Period 2). ADLIB animals had ad libitum access to feed across both periods 1 and 2. At the end of each period, 15 animals from each treatment group were slaughtered, jejunal epithelium collected and RNAseq analysis performed. Animals that were previously diet restricted underwent CG, gaining 1.8 times the rate of their non-restricted counterparts. Twenty-four genes were differentially expressed in RES compared to ADLIB animals at the end of Period 1, with only one gene, GSTA1, differentially expressed between the two groups at the end of Period 2. When analysed within treatment (RES, Period 2 v Period 1), 31 genes were differentially expressed between diet restricted and animals undergoing CG. Dietary restriction and subsequent re-alimentation were associated with altered expression of genes involved in digestion and metabolism as well as those involved in cellular division and growth. Compensatory growth was also associated with greater expression of genes involved in cellular protection and detoxification in jejunal epithelium. This study highlights some of the molecular mechanisms regulating the response to dietary restriction and subsequent re-alimentation induced CG in cattle; however the gene expression results suggest that most of the CG in jejunal epithelium had occurred by day 55 of re-alimentation.

 

Renal and Hematologic Comparative Effects of Dissociated Agonist of the Glucocorticoid Receptor and Prednisone in Dogs With and Without Food Restriction.

Radi ZA, Vogel WM, LaBranche T, Dybowski JA, Peraza MA, Portugal SS, Lettiere DJ.

Int J Toxicol. 2018 Jan 1:1091581818763804. doi: 10.1177/1091581818763804. [Epub ahead of print]

PMID: 29554821

Abstract

Glomerulopathy and body weight gain were noted after chronic oral administration of a novel nonsteroidal dissociated agonist of the glucocorticoid receptor compound, fosdagrocorat, to beagle dogs fed an ad libitum diet. To further investigate the role of diet and treatment with either fosdagrocorat or the glucocorticoid comparator, prednisone, on renal safety, a 13-week investigative study was conducted in beagle dogs. Renal histopathology, clinical chemistry, urinalysis, glomerular filtration rate (GFR), body weight, heart rate, blood pressure (BP), and hematology were investigated in restricted- and ad libitum-fed dogs administered prednisone (2.2 mg/kg/d), fosdagrocorat (5 mg/kg/d), or vehicle for 13 weeks. Glomerulopathy was primarily observed in fosdagrocorat- and prednisone-treated ad libitum but not in feed-restricted or ad libitum vehicle-treated dogs. Kidneys in dogs from the prednisone-treated ad libitum had the greatest incidence and severity of tubular degenerative changes. Increased urine volume and decreased urine-specific gravity were present in prednisone- and fosdagrocorat-treated dogs, regardless of diet. These changes were not associated with consistent changes in GFR. Fosdagrocorat or prednisone treatment ad libitum dogs had the greatest increase in body weight gain. Sporadic changes in systolic and diastolic BP were noted in fosdagrocorat- and prednisone-treated groups. Significant reductions in serum cortisol and absolute eosinophils were noted in both ad libitum- and restriction-fed prednisone- and fosdagrocorat-treated dogs. In conclusion, prednisone-treated dogs fed ad libitum had greater glucocorticoid-induced renal effects than those dosed with fosdagrocorat.

KEYWORDS:

glomerulus; nephrotoxicity; renal pathology

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Sirtuins as Mediator of the Anti-Ageing Effects of Calorie Restriction in Skeletal and Cardiac Muscle.

Zullo A, Simone E, Grimaldi M, Musto V, Mancini FP.

Int J Mol Sci. 2018 Mar 21;19(4). pii: E928. doi: 10.3390/ijms19040928. Review.

PMID: 29561771 Free Article

http://www.mdpi.com/1422-0067/19/4/928/htm

Abstract

Fighting diseases and controlling the signs of ageing are the major goals of biomedicine. Sirtuins, enzymes with mainly deacetylating activity, could be pivotal targets of novel preventive and therapeutic strategies to reach such aims. Scientific proofs are accumulating in experimental models, but, to a minor extent, also in humans, that the ancient practice of calorie restriction could prove an effective way to prevent several degenerative diseases and to postpone the detrimental signs of ageing. In the present review, we summarize the evidence about the central role of sirtuins in mediating the beneficial effects of calorie restriction in skeletal and cardiac muscle since these tissues are greatly damaged by diseases and advancing years. Moreover, we entertain the possibility that the identification of sirtuin activators that mimic calorie restriction could provide the benefits without the inconvenience of this dietary style.

KEYWORDS:

ageing; calorie restriction; cardiac muscle; nutrient deprivation; sirtuins; skeletal muscle

 

Predominant gut Lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice.

Pan F, Zhang L, Li M, Hu Y, Zeng B, Yuan H, Zhao L, Zhang C.

Microbiome. 2018 Mar 21;6(1):54. doi: 10.1186/s40168-018-0440-5.

PMID: 29562943 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863386/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863386/pdf/40168_2018_Article_440.pdf

Abstract

BACKGROUND:

Calorie restriction (CR), which has a potent anti-inflammaging effect, has been demonstrated to induce dramatic changes in the gut microbiota. Whether the modulated gut microbiota contributes to the attenuation of inflammation during CR is unknown, as are the members of the microbial community that may be key mediators of this process.

RESULTS:

Here, we report that a unique Lactobacillus-predominated microbial community was rapidly attained in mice within 2 weeks of CR, which decreased the levels of circulating microbial antigens and systemic inflammatory markers such as tumour necrosis factor alpha (TNF-α). Lactobacillus murinus CR147, an isolate in the most abundant operational taxonomic unit (OTU) enriched by CR, downregulated interleukin-8 production in TNF-α-stimulated Caco-2 cells and significantly increased the lifespan and the brood size of the nematode Caenorhabditis elegans. In gnotobiotic mice colonized with the gut microbiota from old mice, this strain decreased their intestinal permeability and serum endotoxin load, consequently attenuating the inflammation induced by the old microbiota.

CONCLUSIONS:

Our study demonstrated that a strain of Lactobacillus murinus was promoted in CR mice and causatively contributed to the attenuation of ageing-associated inflammation.

KEYWORDS:

Calorie restriction; Chronic inflammation; Gut microbiota; Lactobacillus murinus; Lifespan

 

Calorie restriction regime enhances physical performance of trained athletes.

Pons V, Riera J, Capó X, Martorell M, Sureda A, Tur JA, Drobnic F, Pons A.

J Int Soc Sports Nutr. 2018 Mar 9;15:12. doi: 10.1186/s12970-018-0214-2. eCollection 2018.

PMID: 29556158 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845356/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845356/pdf/12970_2018_Article_214.pdf

Abstract

BACKGROUND:

Caloric restriction induces mitochondrial biogenesis and improves physical fitness in rodents. We aimed to provide evidence of how caloric restriction affects the body composition and physical performance of trained athletes and to evaluate the possible impact of an every-other-day feeding diet on nutritional deficiencies of micronutrients and essential fatty acids.

METHODS:

The study was performed with 12 healthy male athletes by carrying out a 33% caloric restriction with respect to their usual diet. Athletes performed a maximal exercise stress test both before and after the caloric restriction period. Blood samples were taken before and after the caloric restriction at basal conditions and 30 min post-exercise. Although energy intake was reduced by about 33%, the contribution of carbohydrates, proteins, and lipids to total energy intake during the caloric restriction was similar to the original diet.

RESULTS:

The caloric restriction reduced the daily specific micronutrient intake to values lower than 90% of recommended dietary allowances. No effects were observed in blood parameters related to iron metabolism and tissue damage, glucose levels, lipid profiles, or erythrocyte fatty acid composition. In addition, oxidative damage markers decreased after the nutritional intervention. The caloric restriction intervention significantly reduced body weight and trunk, arm, and leg weights; it also caused a decrease in fat and lean body mass, the energy expenditure rate when performing a maximal exercise stress test, and the energy cost to run one meter at various exercise intensities. Furthermore, the intervention ameliorated the onset of the anaerobic phase of exercise.

CONCLUSION:

A caloric restriction improves athletes' performance and energy efficiency, but reduces the daily intake of micronutrients; so, when caloric restriction programs are implemented micronutrient supplementation should be considered.

KEYWORDS:

Body composition; Caloric restriction; Fatty acids; Physical performance

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Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging.

Redman LM, Smith SR, Burton JH, Martin CK, Il'yasova D, Ravussin E.

Cell Metab. 2018 Mar 12. pii: S1550-4131(18)30130-X. doi: 10.1016/j.cmet.2018.02.019. [Epub ahead of print]

PMID: 29576535

Abstract

Calorie restriction (CR) is a dietary intervention with potential benefits for healthspan improvement and lifespan extension. In 53 (34 CR and 19 control) non-obese adults, we tested the hypothesis that energy expenditure (EE) and its endocrine mediators are reduced with a CR diet over 2 years. Approximately 15% CR was achieved over 2 years, resulting in an average 8.7 kg weight loss, whereas controls gained 1.8 kg. In the CR group, EE measured over 24 hr or during sleep was approximately 80-120 kcal/day lower than expected on the basis of weight loss, indicating sustained metabolic adaptation over 2 years. This metabolic adaptation was accompanied by significantly reduced thyroid axis activity and reactive oxygen species (F2-isoprostane) production. Findings from this 2-year CR trial in healthy, non-obese humans provide new evidence of persistent metabolic slowing accompanied by reduced oxidative stress, which supports the rate of living and oxidative damage theories of mammalian aging.

KEYWORDS:

aging; energy expenditure; intervention; nutrition

 

Anti-nociceptive effects of caloric restriction on neuropathic pain in rats involves silent information regulator 1.

Liu Y, Ni Y, Zhang W, Sun YE, Jiang M, Gu WJ, Ma ZL, Gu XP.

Br J Anaesth. 2018 Apr;120(4):807-817. doi: 10.1016/j.bja.2017.09.009. Epub 2018 Jan 17.

PMID: 29576121

Abstract

BACKGROUND:

Caloric restriction (CR) increases both average and maximum lifespan, retards physiological signs of ageing, and delays the onset of several diseases and may mediate neuropathic pain. Neuropathic pain seriously affects the quality of life of patients. In this study, we investigated whether CR exerts anti-nociceptive effects on neuropathic pain, and probed its potential mechanisms.

METHODS:

Adult rats were divided into two dietary groups: an ad libitum (AL)-fed group and a CR group, which was provided with 60% of the food intake of AL rats for 6 weeks. The effects of 6-week CR on pain behaviour and neuro-inflammation induced by chronic constriction injury of the sciatic nerve were evaluated.

RESULTS:

Rats subjected to a CR diet had reduced hypersensitivity to mechanical and thermal stimuli after nerve-constriction injury. CR increased the silent information regulator 1 (SIRT1) expression, and suppressed the nerve-constriction-induced production of mitochondrial-derived reactive oxygen species and activation of nuclear factor kappa B accompanied by suppression of mature interleukin-1β production in the ipsilateral spinal cord dorsal horn. The inhibition of SIRT1 reversed the effects of caloric restriction on pain behaviours. Moreover, CR decreased the phosphorylation of N-methyl-d-aspartate receptor subunits and the mitogen-activated protein kinase family, decreased the sensory neurone excitability, and inhibited the nerve-constriction-induced glial-cell activation.

CONCLUSIONS:

These results suggest that the effects of CR on pain behaviours in a rat model of nerve injury are via inhibition of excessive neuro-inflammation induced by the injury. CR may be of benefit in patients with neuropathic pain.

KEYWORDS:

SIRT1 protein; caloric restriction; neuropathic pain

 

Dietary Restriction Ameliorates Age-Related Increase in DNA Damage, Senescence and Inflammation in Mouse Adipose Tissuey.

Ishaq A, Schröder J, Edwards N, von Zglinicki T, Saretzki G.

J Nutr Health Aging. 2018;22(4):555-561. doi: 10.1007/s12603-017-0968-2.

PMID: 29582897 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866821/

Abstract

Ageing is associated with redistribution of fat around the body and saturation of visceral adipose depots. Likewise, the presence of excess fat in obesity or during ageing places extra stress on visceral depots, resulting in chronic inflammation and increased senescence. This process can contribute to the establishment of the metabolic syndrome and accelerated ageing. Dietary restriction (DR) is known to alleviate physiological signs of inflammation, ageing and senescence in various tissues including adipose tissue.

OBJECTIVES:

Our pilot study aimed to analyse senescence and inflammation parameters in mouse visceral fat tissue during ageing and by short term, late-onset dietary restriction as a nutritional intervention. Design, measurements: In this study we used visceral adipose tissue from mice between 5 and 30 months of age and analysed markers of senescence (adipocyte size, γH2A.X, p16, p21) and inflammation (e.g. IL-6, TNFα, IL-1β, macrophage infiltration) using immuno-staining, as well as qPCR for gene expression analysis. Fat tissues from 3 mice per group were analysed.

RESULTS:

We found that the amount of γH2A.X foci as well as the expression of senescence and inflammation markers increased during ageing but decreased with short term DR. In contrast, the increase in amounts of single or aggregated macrophages in fat depots occurred only at higher ages. Surprisingly, we also found that adipocyte size as well as some senescence parameters decreased at very high age (30 months).

CONCLUSIONS:

Our results demonstrate increased senescence and inflammation during ageing in mouse visceral fat while DR was able to ameliorate several of these parameters as well as increased adipocyte size at 17.5 months of age. This highlights the health benefits of a decreased nutritional intake over a relatively short period of time at middle age.

KEYWORDS:

Visceral fat, ageing; dietary restriction; inflammation; senescence

 

Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging.

Yin Z, Raj DD, Schaafsma W, van der Heijden RA, Kooistra SM, Reijne AC, Zhang X, Moser J, Brouwer N, Heeringa P, Yi CX, van Dijk G, Laman JD, Boddeke EWGM, Eggen BJL.

Front Mol Neurosci. 2018 Mar 12;11:65. doi: 10.3389/fnmol.2018.00065. eCollection 2018.

PMID: 29593493 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857900/

Abstract

Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

KEYWORDS:

aging; caloric restriction; high-fat diet; low-fat diet; microglia; neuroinflammation; physical exercise

 

Impact of intermittent fasting on the lipid profile: Assessment associated with diet and weight loss.

Santos HO, Macedo RCO.

Clin Nutr ESPEN. 2018 Apr;24:14-21. doi: 10.1016/j.clnesp.2018.01.002. Review.

PMID: 29576352

Abstract

Intermittent fasting, whose proposed benefits include the improvement of lipid profile and the body weight loss, has gained considerable scientific and popular repercussion. This review aimed to consolidate studies that analyzed the lipid profile in humans before and after intermittent fasting period through a detailed review; and to propose the physiological mechanism, considering the diet and the body weight loss. Normocaloric and hypocaloric intermittent fasting may be a dietary method to aid in the improvement of the lipid profile in healthy, obese and dyslipidemic men and women by reducing total cholesterol, LDL, triglycerides and increasing HDL levels. However, the majority of studies that analyze the intermittent fasting impacts on the lipid profile and body weight loss are observational based on Ramadan fasting, which lacks large sample and detailed information about diet. Randomized clinical trials with a larger sample size are needed to evaluate the IF effects mainly in patients with dyslipidemia.

KEYWORDS:

Clinical analysis; Diet; Fasting; Lipids

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Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation.

Hadad N, Unnikrishnan A, Jackson JA, Masser DR, Otalora L, Stanford DR, Richardson A, Freeman WM.

Neurobiol Aging. 2018 Mar 16;67:53-66. doi: 10.1016/j.neurobiolaging.2018.03.009. [Epub ahead of print]

PMID: 29631215

Abstract

Brain aging is marked by cognitive decline and susceptibility to neurodegeneration. Calorie restriction (CR) increases neurogenesis, improves memory function, and protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital to normal central nervous system cellular and memory functions and are dysregulated with aging. The beneficial effects of CR have been proposed to work through epigenetic processes, but this is largely unexplored. We therefore tested whether life long CR prevents age-related hippocampal DNA methylation changes. Hippocampal DNA from young (3 months) and old (24 months) male mice fed ad libitum and 24-month-old mice fed a 40% calorie-restricted diet from 3 months of age were examined by genome-wide bisulfite sequencing to measure methylation with base specificity. Over 27 million CG and CH (non-CG) sites were examined. Of the ∼40,000 differentially methylated CG and ∼80,000 CH sites with aging, >1/3 were prevented by CR and were found across genomic regulatory regions and gene pathways. CR also caused alterations to CG and CH methylation at sites not differentially methylated with aging, and these CR-specific changes demonstrated a different pattern of regulatory element and gene pathway enrichment than those affected by aging. CR-specific DNA methyltransferase 1 and Tet methylcytosine dioxygenase 3 promoter hypermethylation corresponded to reduced gene expression. These findings demonstrate that CR attenuates age-related CG and CH hippocampal methylation changes, in combination with CR-specific methylation that may also contribute to the neuroprotective effects of CR. The prevention of age-related methylation alterations is also consistent with the prolongevity effects of CR working through an epigenetic mechanism.

KEYWORDS:

Aging; Caloric restriction; DNA methylation; Epigenetics; Hippocampus

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Effects of replacing diet beverages with water on weight loss and weight maintenance: 18-month follow-up, randomized clinical trial.

Madjd A, Taylor MA, Delavari A, Malekzadeh R, Macdonald IA, Farshchi HR.

Int J Obes (Lond). 2017 Dec 21. doi: 10.1038/ijo.2017.306. [Epub ahead of print]

Abstract

BACKGROUND:

Beneficial effects of replacing diet beverages (DBs) with water on weight loss, during a 24-week hypoenergetic diet were previously observed. However, it is not known whether this difference is sustained during a subsequent 12-month weight maintenance period.

OBJECTIVE:

To evaluate effects of replacing DBs with water on body weight maintenance over a 12-month period in participants who undertook a 6-month weight loss plan.

DESIGN:

Seventy-one obese and overweight adult women (body mass index (BMI): 27-40 kg m-2; age: 18-50 years) who usually consumed DBs in their diet were randomly assigned to either substitute water for DBs (water group: 35) or continue drinking DBs five times per week (DBs group: 36) after their lunch for the 6-month weight loss intervention and subsequent 12-month weight maintenance program.

RESULTS:

A total of 71 participants who were randomly assigned were included in the study by using an intention-to-treat analysis. Greater additional weight loss (mean±s.d.) in the water group was observed compared with the DBs group after the 12-month follow-up period (-1.7±2.8 vs -0.1±2.7 kg, P=0.001). BMI decreased more in the water group than in the DBs group (-0.7±1 vs -0.05±1.1 kg m-2, P=0.003). There was also a greater reduction in fasting insulin levels (-0.5±1.4 vs -0.02±1.5 mmol l-1, P=0.023), better improvement in homeostasis model assessment of insulin resistance (-0.2±0.4 vs -0.1±0.3, P=0.013) and a greater decrease in 2-h postprandial plasma glucose (-0.2±0.3 vs -0.1±0.3 mmol l-1, P<0.001) in the water group compared with the DBs over the 12-month weight maintenance period.

CONCLUSIONS:

Replacement of DBs with water after the main meal in women who were regular users of DBs may cause further weight reduction during a 12-month weight maintenance program. It may also offer benefits in carbohydrate metabolism including improvement of insulin resistance over the long-term weight maintenance period.

PMID: 29633983

>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>

Effects on weight loss in adults of replacing diet beverages with water during a hypoenergetic diet: a randomized, 24-wk clinical trial.

Madjd A, Taylor MA, Delavari A, Malekzadeh R, Macdonald IA, Farshchi HR.

Am J Clin Nutr. 2015 Dec;102(6):1305-12. doi: 10.3945/ajcn.115.109397. Epub 2015 Nov 4.

PMID: 26537940

https://watermark.silverchair.com/ajcn109397.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAa0wggGpBgkqhkiG9w0BBwagggGaMIIBlgIBADCCAY8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMnY1SDsCjQxsDE1BFAgEQgIIBYBLL7jaEBJliris_Nfyr1hgHGUF3u71R9ADyTg0tT1kayehNLa-4EWruN2dEwPSmu56KSNndH1l3MM3Am0ims0Ew1rm16wMEa3EyAvh-kpxbD1RNk43XGuE07KayXU2enyi_RYT-COR1DLWhHIGH4dICBFdB7H45lONMbtfOd-ZGiL8w8Xa9Bvgtk3BKm3R7rAsUzvz8ySbRAQztR27rFNPdcMe1isINcfXw03cMGqt6Nxl2Y91oEKYR_LEIaPkD4dXMVVgS56zgdtFk75rKt1PGuPBb_oqk57NiXbpBZjvFhkNPHDrMo2sn-ftY4FD_t7ufwXLtjCJ0S7ZV5S1O7ZzY-DMRwe6W-TR6hIuaAIc8SO8y7NGHCTMGROOOJ-iK3j_ydsyLM3n7DFPFN6ZbZS1VEmJmDbjWYdWFoNCIdFnVqDdtpeppOBaaDDtREErDouG3ZjibcTVSq_SBTalFLn4

Abstract

BACKGROUND:

Obese people believe that drinking diet beverages (DBs) may be a simple strategy to achieve weight loss. However, nutritionists advise drinking water when attempting to lose weight. It is unclear how important drinking water instead of DBs is during a weight-loss program.

OBJECTIVE:

In this study, we compared the effect on weight loss of either replacing DBs with water or continuing to consume DBs in adults during a 24-wk weight-loss program.

DESIGN:

Overweight and obese women [n = 89; body mass index (BMI; in kg/m(2)): 27-40; age: 18-50 y] who usually consumed DBs in their diet were asked to either substitute water for DBs (water group) or continue drinking DBs 5 times/wk after their lunch for 24 wk (DB group) while on a weight-loss program.

RESULTS:

Sixty-two participants (71%) completed the trial (32 in the DB group, 30 in the water group). Baseline variables were not statistically significantly different between groups. A statistically significant reduction in anthropometric measurements and statistically significant improvements in cardiometabolic risk characteristics were observed over 24 wk in both groups. Compared with the DB group, the water group had a greater decrease in weight (mean ± SD: water: -8.8 ± 1.9 kg; DBs: -7.6 ± 2.1 kg; P = 0.015, time × group), fasting insulin (mean ± SD: water: -2.84 ± 0.77 mU/L; DBs: -1.78 ± 1.25 mU/L, P < 0.001), homeostasis model assessment of insulin resistance (mean ± SD: water: -0.097 ± 0.049; DBs: -0.057 ± 0.042, P < 0.001), and 2-h postprandial glucose (mean ± SD: water: -1.02 ± 0.25 mmol/L; DBs: -0.72 ± 0.27 mmol/L; P < 0.001) over the 24 wk. However, there was no significant time × group interaction for waist circumference, fasting plasma glucose, and lipid profiles within both groups over 24 wk.

CONCLUSIONS:

Replacement of DBs with water after the main meal may lead to greater weight reduction during a weight-loss program. It may also offer clinical benefits to improve insulin resistance. This trial was registered at www.irct.ir/ as IRCT201402177754N5.

KEYWORDS:

diet beverages; insulin resistance; obesity; water; weight loss

 

Calorie restriction is the most reasonable anti-ageing intervention: a meta-analysis of survival curves.

Liang Y, Liu C, Lu M, Dong Q, Wang Z, Wang Z, Xiong W, Zhang N, Zhou J, Liu Q, Wang X, Wang Z.

Sci Rep. 2018 Apr 10;8(1):5779. doi: 10.1038/s41598-018-24146-z.

PMID: 29636552

https://www.nature.com/articles/s41598-018-24146-z

https://www.nature.com/articles/s41598-018-24146-z.pdf

Abstract

Despite technological advances, the survival records from longevity experiments remain the most indispensable tool in ageing-related research. A variety of interventions, including medications, genetic manipulations and calorie restriction (CR), have been demonstrated to extend the lifespan of several species. Surprisingly, few systematic studies have investigated the differences among these anti-ageing strategies using survival data. Here, we conduct a comprehensive and comparative meta-analysis of numerous published studies on Caenorhabditis elegans and Drosophila. We found that CR and genetic manipulations are generally more effective than medications at extending the total lifespan in both models, and CR can improve the ageing pattern of C. elegans. We further analysed the survival variation for different anti-ageing medications and determined that hypoglycaemic agents and antioxidants are advantageous despite only moderately increasing the overall lifespan; therefore, these two types of medications are promising CR mimetics. Analysis of genetic manipulations also indicated that the genes or pathways that extend lifespan in a healthier pattern are associated with CR. These results suggest that CR or CR mimetics may be the most reasonable and potentially beneficial anti-ageing strategy.

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Dietary restriction slightly affects glucose homeostasis and delays plasma cholesterol removal in rabbits with dietary lipid lowering.

Yu Q, Liu R, Han L, Zhang G, Guan H, Pan Q, Wang S, Liu E.

Appl Physiol Nutr Metab. 2018 Apr 15. doi: 10.1139/apnm-2017-0876. [Epub ahead of print]

PMID: 29658290

Abstract

Dietary restriction (DR) has been reported to promote the beneficial effects on atherosclerotic progression, lipid and glucose metabolism, but little is known about these effects can be enhanced or weakened by dietary lipid lowering. After 12 weeks of the high-cholesterol diet (HCD) feeding, hypercholesterolemic rabbits were fed with either a chow diet ad libitum (AL) or a chow diet with DR for 16 weeks of dietary lipid lowering. Here, we found the DR group exhibited a loss in body weight, small internal organs and the reduced fat mass, but the AL group accumulated more subcutaneous fat than the baseline group. DR treatment slightly worsened glucose tolerance but enhanced insulin sensitivity, and a slight effect of DR on insulin secretion was also observed. After diet cholesterol withdrawal, rabbits showed persistently lowering of total cholesterol and triglyceride in plasma. The DR group had significantly higher plasma total cholesterol than the AL group at the most time points during 7 to 16 weeks of lipid lowering. Although both AL and DR groups developed more severe atherosclerosis than baseline group, DR did not improve atherosclerotic progression and the accumulation of macrophages and smooth muscle cells as well. We concluded that DR affected glucose and lipid metabolism but did not ameliorate atherosclerosis in rabbits when associated with lipid lowering by the dietary cholesterol withdrawal.

 

A Comparative Approach to Metabolic Aspects of Aging: Conserved Mechanisms and Effects of Calorie Restriction and Environment.

Ottinger MA.

Prog Mol Biol Transl Sci. 2018;155:109-127. doi: 10.1016/bs.pmbts.2017.11.004. Epub 2018 Feb 6.

PMID: 29653678

Abstract

Metabolic systems and the function of these systems are complex, involving biochemical pathways, endocrine, neuroendocrine systems, and physiological systems and interact with environmental conditions. Studies in animal models have been invaluable in gaining an understanding of the mechanisms involved in metabolic endocrine changes during normal aging and with conditions, such as diabetes and obesity. Together, these studies have revealed some conserved mechanisms and identified specific biomarkers of aging related to metabolic changes. Further, characterization of these mechanisms provides an opportunity to develop interventions and treatments for both humans and other vertebrates. This chapter will provide an overview of age-related changes in metabolism from studies in human populations and the perspective of information gained from comparative animal models. Detailed molecular mechanisms and endocrine pathways have already been discussed in other chapters of this volume. Finally, calorie restriction (CR) has shown consistent benefit to age-related disease incidence with effects that has been consistent across animal models These studies on the effects of CR enable further discernment of disease versus healthy aging processes.

KEYWORDS:

aging; calorie restriction; comparative models; metabolism

 

Obesity, Metabolism, and Aging: A Multiscalar Approach.

Bentley RA, Ross CN, O'Brien MJ.

Prog Mol Biol Transl Sci. 2018;155:25-42. doi: 10.1016/bs.pmbts.2017.11.016. Epub 2018 Feb 1.

PMID: 29653680

Abstract

Obesity contributes to the aging process through the alteration of metabolic pathways evidenced biochemically in the relationship between caloric restriction and longevity. Humans have entered into an era of metabolism and aging entirely unprecedented in their evolution, with a diet that, for many, contains a majority of calories as sugar and yields an expected lifespan of over 80years in industrialized nations. Deeply embedded in the complex issue of obesity are questions of behavior, causality versus correlation, and appropriate models. For example, are primates a better reference than mice for studying metabolic connections between obesity and aging? We consider those issues from the standpoint of life-history theory, especially implications of the interplay of refined sugar and socioeconomic disparities for the future of human health.

KEYWORDS:

aging; caloric restriction; life-history theory; longevity; metabolic pathways; obesity

 

Metabolic Aspects of Aging.

Fridell YW, Sierra F.

Prog Mol Biol Transl Sci. 2018;155:11-23. doi: 10.1016/bs.pmbts.2017.12.015. Epub 2018 Feb 24.

PMID: 29653679

Abstract

Metabolic interventions involving undernutrition but not malnutrition (e.g., caloric restriction, CR) are effective strategies for improving both health and longevity in species ranging from lower organisms to nonhuman primates. Initial human trials to test the effects of sustained, reduced energy intake have yielded promising health benefits. Through intense research efforts in understanding the molecular mechanisms of CR, three cellular pathways have now been identified although the precise details remain unknown. More recently, circadian regulation has been recognized as a novel mediator for CR effects in mice. Harnessing the molecular insights into CR, novel nutritional interventions and pharmacological application of CR mimetics have been tested showing great promise in simultaneously improving metabolic function and providing overall health benefits. Additional research is needed to identify efficacious therapeutics that can be safely and practically translated to human studies in promoting healthspan.

KEYWORDS:

CALERIE; aging; caloric restriction; circadian rhythm; dietary restriction; healthspan; lifespan; metabolism; nicotinamide adenine dinucleotide (NAD+); protein restriction

 

Simulating long-term human weight-loss dynamics in response to calorie restriction.

Guo J, Brager DC, Hall KD.

Am J Clin Nutr. 2018 Apr 1;107(4):558-565. doi: 10.1093/ajcn/nqx080.

PMID: 29635495

Abstract

BACKGROUND:

Mathematical models have been developed to predict body weight (BW) and composition changes in response to lifestyle interventions, but these models have not been adequately validated over the long term.

OBJECTIVE:

We compared mathematical models of human BW dynamics underlying 2 popular web-based weight-loss prediction tools, the National Institutes of Health Body Weight Planner (NIH BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC WLP), with data from the 2-year Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study.

DESIGN:

Mathematical models were initialized using baseline CALERIE data, and changes in body weight (ΔBW), fat mass (ΔFM), and energy expenditure (ΔEE) were simulated in response to time-varying changes in energy intake (ΔEI) objectively measured using the intake-balance method. No model parameters were adjusted from their previously published values.

RESULTS:

The PBRC WLP model simulated an exaggerated early decrease in EE in response to calorie restriction, resulting in substantial underestimation of the observed mean (95% CI) BW losses by 3.8 (3.5, 4.2) kg. The NIH WLP simulations were much closer to the data, with an overall mean ΔBW bias of -0.47 (-0.92, -0.015) kg. Linearized model analysis revealed that the main reason for the PBRC WLP model bias was a parameter value defining how spontaneous physical activity expenditure decreased with caloric restriction. Both models exhibited substantial variability in their ability to simulate individual results in response to calorie restriction. Monte Carlo simulations demonstrated that ΔEI measurement uncertainties were a major contributor to the individual variability in NIH BWP model simulations.

CONCLUSIONS:

The NIH BWP outperformed the PBRC WLP and accurately simulated average weight-loss and energy balance dynamics in response to long-term calorie restriction. However, the substantial variability in the NIH BWP model predictions at the individual level suggests cautious interpretation of individual-level simulations.

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Caloric restriction delays yeast chronological aging by remodeling carbohydrate and lipid metabolism, altering peroxisomal and mitochondrial functionalities, and postponing the onsets of apoptotic and liponecrotic modes of regulated cell death.

Arlia-Ciommo A, Leonov A, Beach A, Richard VR, Bourque SD, Burstein MT, Kyryakov P, Gomez-Perez A, Koupaki O, Feldman R, Titorenko VI.

Oncotarget. 2018 Mar 5;9(22):16163-16184. doi: 10.18632/oncotarget.24604. eCollection 2018 Mar 23.

PMID: 29662634

Abstract

A dietary regimen of caloric restriction delays aging in evolutionarily distant eukaryotes, including the budding yeast Saccharomyces cerevisiae. Here, we assessed how caloric restriction influences morphological, biochemical and cell biological properties of chronologically aging yeast advancing through different stages of the aging process. Our findings revealed that this low-calorie diet slows yeast chronological aging by mechanisms that coordinate the spatiotemporal dynamics of various cellular processes before entry into a non-proliferative state and after such entry. Caloric restriction causes a stepwise establishment of an aging-delaying cellular pattern by tuning a network that assimilates the following: 1) pathways of carbohydrate and lipid metabolism; 2) communications between the endoplasmic reticulum, lipid droplets, peroxisomes, mitochondria and the cytosol; and 3) a balance between the processes of mitochondrial fusion and fission. Through different phases of the aging process, the caloric restriction-dependent remodeling of this intricate network 1) postpones the age-related onsets of apoptotic and liponecrotic modes of regulated cell death; and 2) actively increases the chance of cell survival by supporting the maintenance of cellular proteostasis. Because caloric restriction decreases the risk of cell death and actively increases the chance of cell survival throughout chronological lifespan, this dietary intervention extends longevity of chronologically aging yeast.

KEYWORDS: caloric restriction; cellular aging; metabolism; mitochondria; yeast

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Tissue-specific transcriptome profiling of <i>Drosophila</i> reveals roles for GATA transcription factors in longevity by dietary restriction.

Dobson AJ, He X, Blanc E, Bolukbasi E, Feseha Y, Yang M, Piper MDW.

NPJ Aging Mech Dis. 2018 Apr 17;4:5. doi: 10.1038/s41514-018-0024-4. eCollection 2018.

PMID: 29675265

https://www.nature.com/articles/s41514-018-0024-4

Abstract

Dietary restriction (DR) extends animal lifespan, but imposes fitness costs. This phenomenon depends on dietary essential amino acids (EAAs) and TOR signalling, which exert systemic effects. However, the roles of specific tissues and cell-autonomous transcriptional regulators in diverse aspects of the DR phenotype are unknown. Manipulating relevant transcription factors (TFs) specifically in lifespan-limiting tissues may separate the lifespan benefits of DR from the early-life fitness costs. Here, we systematically analyse transcription across organs of Drosophila subjected to DR or low TOR and predict regulatory TFs. We predict and validate roles for the evolutionarily conserved GATA family of TFs, and identify conservation of this signal in mice. Importantly, restricting knockdown of the GATA TF srp to specific fly tissues recapitulated the benefits but not the costs of DR. Together, our data indicate that the GATA TFs mediate effects of dietary amino acids on lifespan, and that by manipulating them in specific tissues it is possible to reap the fitness benefits of EAAs, decoupled from a cost to longevity.

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Effect of whey protein supplementation on body composition changes in women: a systematic review and meta-analysis.

Bergia RE 3rd, Hudson JL, Campbell WW.

Nutr Rev. 2018 Apr 23. doi: 10.1093/nutrit/nuy017. [Epub ahead of print]

PMID: 29688559

Abstract

CONTEXT:

A preponderance of evidence supports the beneficial effects of whey protein (WP) supplementation on body composition in men; however, there is currently insufficient evidence to make an equivalent claim in women.

OBJECTIVE:

This systematic review and meta-analysis assessed the effects of WP supplementation with or without energy restriction (ER) and resistance training (RT) on changes in body mass, lean mass, and fat mass in women.

DATA SOURCES:

Pubmed, Scopus, Cochrane, and CINAHL were searched using the keywords "whey protein," "body composition," and "lean mass."

DATA EXTRACTION:

Two researchers independently screened 1845 abstracts and extracted 276 articles. Thirteen randomized controlled trials with 28 groups met the inclusion criteria.

RESULTS:

Globally, WP supplementation increased lean mass (WMD, 0.37 kg; 95% confidence interval [CI], 0.06 to 0.67) while not influencing changes in fat mass (-0.20 kg; 95%CI, -0.67 to 0.27) relative to non-WP control. The beneficial effect of WP on lean mass was lost when only studies with RT were included in the analysis (n = 7 comparisons; 0.23 kg; 95%CI, -0.17 to 0.63). The beneficial effect of WP on lean mass was more robust when only studies with an ER component were included (n = 6 comparisons; 0.90 kg; 95%CI, 0.31 to 1.49). There was no effect of WP on lean mass in studies without ER (n = 9 comparisons; 0.22 kg; 95%CI, -0.12 to 0.57).

CONCLUSION:

Whey protein supplementation improves body composition by modestly increasing lean mass without influencing changes in fat mass. Body composition improvements from WP are more robust when combined with ER .

 

Energy restriction, exercise and atorvastatin treatment improve endothelial dysfunction and inhibit miRNA-155 in the erectile tissue of the aged rat.

Rocha B, Rodrigues AR, Tomada I, Martins MJ, Guimarães JT, Gouveia AM, Almeida H, Neves D.

Nutr Metab (Lond). 2018 Apr 16;15:28. doi: 10.1186/s12986-018-0265-z. eCollection 2018.

PMID: 29686722

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-018-0265-z

Abstract

BACKGROUND:

Endothelial dysfunction underlies cardiovascular disease that frequently affects aged individuals. Characterized by local decrease in nitric oxide, it results from down-regulation of endothelial nitric oxide synthase (eNOS) expression/activity. Aiming to elucidate the molecular mechanisms involved in age-related endothelial dysfunction and to unveil potential therapeutic targets, we tested how diet pattern, exercise and atorvastatin modulate the expression of eNOS, inducible NOS (iNOS), endothelin-1, sirtuins (SIRT) and microRNA-155 in the erectile tissue of high-fat fed aged rats.

METHODS:

Sprague-Dawley male rats fed with high-fat diet until they completed 12 months were grouped and subjected to energy restriction (ER), ER and atorvastatin, or, ER, atorvastatin and physical exercise. Controls were fed with standard rodent chow. The blood pressure was measured using the tail-cuff method before sacrifice at 18 months. Glucose, total cholesterol, HDL, triglyceride and CRP were assessed in blood and eNOS, endothelin-1, iNOS and sirtuins were detected by immunofluorescence in the penis sections; eNOS, endothelin-1, iNOS, SIRT2-4 and SIRT6-7 were semi-quantified by western blotting in tissue homogenates. MicroRNA-155 was quantified using RT-PCR in formalin-fixed paraffin embedded sections. To compare the studied variables, two-tail student t test was used.

RESULTS:

Atorvastatin promotes eNOS expression and is more efficient than ER or exercise in the control of hyperlipidemia and inflammation. Among the studied sirtuins, detected for the first time in the erectile tissue of the aged rat, SIRT2 aligns with eNOS expression. Both proteins exhibit over-expression in animals with combined exercise, atorvastatin and ER. Analysis of microRNA-155 expression also suggests its intervention in the regulation of eNOS expression. ER, particularly when combined with atorvastatin, was able to reverse the increase of iNOS and endothelin-1 in high-fat fed rats.

CONCLUSIONS:

The present results indicate that the association of ER, atorvastatin and exercise is more efficient than isolated interventions in the prevention of endothelial dysfunction.

KEYWORDS:

Atorvastatin; Endothelial dysfunction; Energy restriction; Exercise; Sirtuins; microRNA-155

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Effects of Different Weight Loss Approaches on CVD Risk.

Clifton PM, Keogh JB.

Curr Atheroscler Rep. 2018 Apr 25;20(6):27. doi: 10.1007/s11883-018-0728-8. Review.

PMID: 29696385

Abstract

PURPOSE OF REVIEW:

In this review, we aimed to answer the question as to whether deliberate weight loss can reduce cardiovascular events or improve cardiovascular risk factors and whether different methods of weight loss can have a differential effect on risk factor improvement.

RECENT FINDINGS:

It would appear that deliberate weight loss reduces total mortality by 16% in obese people with risk factors including type 2 diabetes. People with type 2 diabetes who lose at least 10% of their initial body weight reduce CVD end points by 21% with dietary weight loss while the effect is greater with the greater weight loss induced by bariatric surgery with a 32% reduction in events. Mortality reduction may vary from 29 to up to 79%. Replacing some carbohydrate with protein appears to enhance weight maintenance over 12 months and in addition lowers serum triglyceride and blood pressure. A very-low-carbohydrate diet elevates LDL cholesterol when a high saturated fat "Atkins" style approach is used, but a high unsaturated fat version is safe and effective over a 12-month period and reduces medication requirements in people with type 2 diabetes. A very-low-calorie liquid diet produces excellent weight loss in the short-term, but long-term weight loss is no different to less restrictive dieting. Weight loss lowers CVD events and total mortality and a higher protein (18-25% of energy), lower carbohydrate (< 45% of energy) diet may be superior for weight maintenance and risk factor improvement, but there are no data on event reduction.

KEYWORDS:

Bariatric surgery; Carbohydrate; Cardiovascular disease; Dietary weight loss; Protein; Total mortality

 

Necroptosis increases with age and is reduced by dietary restriction.

Deepa SS, Unnikrishnan A, Matyi S, Hadad N, Richardson A.

Aging Cell. 2018 Apr 25:e12770. doi: 10.1111/acel.12770. [Epub ahead of print]

PMID: 29696779

https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.12770

Abstract

Necroptosis is a newly identified programmed cell death pathway that is highly proinflammatory due to the release of cellular components that promote inflammation. To determine whether necroptosis might play a role in inflammaging, we studied the effect of age and dietary restriction (DR) on necroptosis in the epididymal white adipose tissue (eWAT), a major source of proinflammatory cytokines. Phosphorylated MLKL and RIPK3, markers of necroptosis, were increased 2.7- and 1.9-fold, respectively, in eWAT of old mice compared to adult mice, and DR reduced P-MLKL and P-RIPK3 to levels similar to adult mice. An increase in the expression of RIPK1 (1.6-fold) and MLKL (2.7-fold), not RIPK3, was also observed in eWAT of old mice, which was reduced by DR in old mice. The increase in necroptosis was paralleled by an increase in 14 inflammatory cytokines, including the pro-inflammatory cytokines IL-6 (3.9-fold), TNF-α (4.7-fold), and IL-1β (5.1-fold)], and 11 chemokines in old mice. DR attenuated the expression of IL-6, TNF-α, and IL-1β as well as 85% of the other cytokines/chemokines induced with age. In contrast, inguinal WAT (iWAT), which is less inflammatory, did not show any significant increase with age in the levels of P-MLKL and MLKL or inflammatory cytokines/chemokines. Because the changes in biomarkers of necroptosis in eWAT with age and DR paralleled the changes in the expression of pro-inflammatory cytokines, our data support the possibility that necroptosis might play a role in increased chronic inflammation observed with age.

KEYWORDS:

adipose tissue; aging; dietary restriction; inflammaging; inflammation; necroptosis

 

Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.

Smith RL, Soeters MR, Wüst RCI, Houtkooper RH.

Endocr Rev. 2018 Apr 24. doi: 10.1210/er.2017-00211. [Epub ahead of print]

PMID: 29697773

Abstract

The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

 

Angiopoietin-like protein 3 and 4 in obesity, type 2 diabetes mellitus, and malnutrition: the effect of weight reduction and realimentation.

Cinkajzlová A, Mráz M, Lacinová Z, Kloučková J, Kaválková P, Kratochvílová H, Trachta P, Křížová J, Haluzíková D, Škrha J, Papežová H, Haluzík M.

Nutr Diabetes. 2018 Apr 25;8(1):21. doi: 10.1038/s41387-018-0032-2.

PMID: 29695708

Abstract

BACKGROUND:

Angiopoietin-like proteins (ANGPTLs) 3 and 4 are circulating factors that participate in the regulation of lipid and glucose metabolism.

SUBJECTS AND METHODS:

We measured serum ANGPTL3 and 4 levels in 23 patients with obesity, 40 patients with obesity and type 2 diabetes mellitus (T2DM), 22 patients with anorexia nervosa (AN), 15 subjects undergoing 72-h fasting, and 12 patients with short bowel syndrome (SBS), and their changes after very-low-calorie diet (VLCD), bariatric surgery, partial realimentation, acute fasting, and parenteral nutrition in order to assess their possible role in metabolic regulations.

RESULTS:

Serum ANGPTL4 levels were higher in obese subjects without/with T2DM (94.50 ± 9.51 and 134.19 ± 7.69 vs. 50.34 ± 4.22 ng/ml, p < 0.001) and lower in subjects with AN relative to healthy control subjects (38.22 ± 4.48 vs. 65.80 ± 7.98 ng/ml, p = 0.002), while serum ANGPTL3 levels demonstrated inverse tendency. Nutritional status had no effect on ANGPTL3 and 4 mRNA expression in adipose tissue. Fasting decreased ANGPTL3 and increased ANGPTL4 levels, while VLCD reduced only ANGPTL3. Bariatric surgery and realimentation of AN or SBS patients had no effect on either ANGPTL. Multiple regression analysis identified BMI as an independent predictor of ANGPTL3; and BMI and HbA1c as independent predictors of ANGPTL4, respectively.

CONCLUSIONS:

Taken together, our data suggest that serum ANGPTL3 and 4 levels are influenced by nutritional status and fasting and could be involved in the metabolic disturbances present in obesity and AN.

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Stable Isotope Labeling Reveals Novel Insights Into Ubiquitin-Mediated Protein Aggregation With Age, Calorie Restriction, and Rapamycin Treatment.

Basisty NB, Liu Y, Reynolds J, Karunadharma PP, Dai DF, Fredrickson J, Beyer RP, MacCoss MJ, Rabinovitch PS.

J Gerontol A Biol Sci Med Sci. 2018 Apr 17;73(5):561-570. doi: 10.1093/gerona/glx047.

PMID: 28958078

Abstract

Accumulation of protein aggregates with age was first described in aged human tissue over 150 years ago and has since been described in virtually every human tissue. Ubiquitin modifications are a canonical marker of insoluble protein aggregates; however, the composition of most age-related inclusions remains relatively unknown. To examine the landscape of age-related protein aggregation in vivo, we performed an antibody-based pulldown of ubiquitinated proteins coupled with metabolic labeling and mass spectrometry on young and old mice on calorie restriction (CR), rapamycin (RP)-supplemented, and control diets. We show increased abundance of many ubiquitinated proteins in old mice and greater retention of preexisting (unlabeled) ubiquitinated proteins relative to their unmodified counterparts-fitting the expected profile of age-increased accumulation of long-lived aggregating proteins. Both CR and RP profoundly affected ubiquitinome composition, half-live, and the insolubility of proteins, consistent with their ability to mobilize these age-associated accumulations. Finally, confocal microscopy confirmed the aggregation of two of the top predicted aggregating proteins, keratins 8/18 and catalase, as well as their attenuation by CR and RP. Stable-isotope labeling is a powerful tool to gain novel insights into proteostasis mechanisms, including protein aggregation, and could be used to identify novel therapeutic targets in aging and protein aggregation diseases.

 

Intermittent Fasting: Is the Wait Worth the Weight?

Stockman MC, Thomas D, Burke J, Apovian CM.

Curr Obes Rep. 2018 Apr 26. doi: 10.1007/s13679-018-0308-9. [Epub ahead of print] Review.

PMID: 29700718

Abstract

PURPOSE OF REVIEW:

We review the underlying mechanisms and potential benefits of intermittent fasting (IF) from animal models and recent clinical trials.

RECENT FINDINGS:

Numerous variations of IF exist, and study protocols vary greatly in their interpretations of this weight loss trend. Most human IF studies result in minimal weight loss and marginal improvements in metabolic biomarkers, though outcomes vary. Some animal models have found that IF reduces oxidative stress, improves cognition, and delays aging. Additionally, IF has anti-inflammatory effects, promotes autophagy, and benefits the gut microbiome. The benefit-to-harm ratio varies by model, IF protocol, age at initiation, and duration. We provide an integrated perspective on potential benefits of IF as well as key areas for future investigation. In clinical trials, caloric restriction and IF result in similar degrees of weight loss and improvement in insulin sensitivity. Although these data suggest that IF may be a promising weight loss method, IF trials have been of moderate sample size and limited duration. More rigorous research is needed.

KEYWORDS:

Calorie restriction; Fasting; Insulin resistance; Intermittent fasting; Metabolism; Obesity; Weight loss

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Overexpression of CYB5R3 and NQO1, two NAD<sup>+</sup> -producing enzymes, mimics aspects of caloric restriction.

Diaz-Ruiz A, Lanasa M, Garcia J, Mora H, Fan F, Martin-Montalvo A, Di Francesco A, Calvo-Rubio M, Salvador-Pascual A, Aon MA, Fishbein KW, Pearson KJ, Villalba JM, Navas P, Bernier M, de Cabo R.

Aging Cell. 2018 Apr 28:e12767. doi: 10.1111/acel.12767. [Epub ahead of print]

PMID: 29706024

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12767

Abstract

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH-dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD+ /sirtuin pathway. The results highlight the importance of these NAD+ producers for the promotion of health and extended lifespan.

KEYWORDS:

CYB5R3; NQO1; aging; calorie restriction; metabolic homeostasis

 

Transcriptional profiling identifies strain-specific effects of caloric restriction and opposite responses in human and mouse white adipose tissue.

Swindell WR, List EO, Berryman DE, Kopchick JJ.

Aging (Albany NY). 2018 Apr 29. doi: 10.18632/aging.101424. [Epub ahead of print]

PMID: 29708498

Abstract

Caloric restriction (CR) has been extensively studied in rodents as an intervention to improve lifespan and healthspan. However, effects of CR can be strain- and species-specific. This study used publically available microarray data to analyze expression responses to CR in males from 7 mouse strains (C57BL/6J, BALB/c, C3H, 129, CBA, DBA, B6C3F1) and 4 tissues (epididymal white adipose tissue (eWAT), muscle, heart, cortex). In each tissue, the largest number of strain-specific CR responses was identified with respect to the C57BL/6 strain. In heart and cortex, CR responses in C57BL/6 mice were negatively correlated with responses in other strains. Strain-specific CR responses involved genes associated with olfactory receptors (Olfr1184, Olfr910) and insulin/IGF-1 signaling (Igf1, Irs2). In each strain, CR responses in eWAT were negatively correlated with those in human subcutaneous WAT (scWAT). In human scWAT, CR increased expression of genes associated with stem cell maintenance and vascularization. However, orthologous genes linked to these processes were down-regulated in mouse. These results identify strain-specific CR responses limiting generalization across mouse strains. Differential CR responses in mouse versus human WAT may be due to differences in the depots examined and/or the presence of "thrifty genes" in humans that resist adipose breakdown despite caloric deficit.

KEYWORDS:

adipose; aging; dietary restriction; insulin; insulin-like growth factor; longevity; microarray; olfactory receptor

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The Effects of Graded Levels of Calorie Restriction: XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice.

Green CL, Soltow QA, Mitchell SE, Derous D, Wang Y, Chen L, Han JJ, Promislow DEL, Lusseau D, Douglas A, Jones DP, Speakman JR.

J Gerontol A Biol Sci Med Sci. 2018 Apr 30. doi: 10.1093/gerona/gly058. [Epub ahead of print]

PMID: 29718123

https://watermark.silverchair.com/gly058.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAdMwggHPBgkqhkiG9w0BBwagggHAMIIBvAIBADCCAbUGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMr1zqTVQRCxpdI1PrAgEQgIIBhkbLb7Rblx5sHa_M_LnV-lgqK2DiHCWmtt8uDJaLAlcJN7u74VqE31f8nWvam1-pWmbnXLFbKkukG8VcfPtjKRZCZER3JGRZuKL2h3z_lxZoK6_ivHYkGfEsDrZ_xBwbOCGAHDSp9uPg9hfA3JJjXU3Zj100PvI1oOhUpBokM7iezyQZhaHT-2Q5NV0H6TDbQqwLzQQ2tMRKe_5H21vjyJeUnPUuN5HBwX3OsiV34CMpEgwcd6J1kzoE8HSn_67HMyf8J8dL2ivNRzrq2Jkkrgid3OoXuJ9NtmttCZssL1er9SfTAXt7vp3xD2n3XEwxDQ7UIDY90oif2_oG3rmw-sfDrlu5DGIbvNNaNgIiD47yjixlakDRYTCHxLRAIHhxpP1z7p2XF-w23EL4JQuIc4MMc_qWo2GLFwqRS-p2YWuPpWZgDyShR6Txt1Mt4OvJTZpWxrkPASn77TPIRg1emLLqC0Gq39yHuekMIu9e5mux6o8PiD9gaqgwGpXs0TH1O7dLDgrtHg

Abstract

Calorie restriction (CR) remains the most robust intervention to extend life span and improve health span. Using a global mass spectrometry-based metabolomics approach, we identified metabolites that were significantly differentially expressed in the plasma of C57BL/6 mice, fed graded levels of calorie restriction (10% CR, 20% CR, 30% CR, and 40% CR) compared with mice fed ad libitum for 12 hours a day. The differential expression of metabolites increased with the severity of CR. Pathway analysis revealed that graded CR had an impact on vitamin E and vitamin B levels, branched chain amino acids, aromatic amino acids, and fatty acid pathways. The majority of amino acids correlated positively with fat-free mass and visceral fat mass, indicating a strong relationship with body composition and vitamin E metabolites correlated with stomach and colon size, which may allude to the beneficial effects of investing in gastrointestinal organs with CR. In addition, metabolites that showed a graded effect, such as the sphinganines, carnitines, and bile acids, match our previous study on liver, which suggests not only that CR remodels the metabolome in a way that promotes energy efficiency, but also that some changes are conserved across tissues.

 

Evolution Under Dietary Restriction Decouples Survival From Fecundity in Drosophila melanogaster Females.

Zajitschek F, Georgolopoulos G, Vourlou A, Ericsson M, Zajitschek SRK, Friberg U, Maklakov AA.

J Gerontol A Biol Sci Med Sci. 2018 Apr 28. doi: 10.1093/gerona/gly070. [Epub ahead of print]

PMID: 29718269

Abstract

One of the key tenets of life-history theory is that reproduction and survival are linked and that they trade-off with each other. When dietary resources are limited, reduced reproduction with a concomitant increase in survival is commonly observed. It is often hypothesized that this dietary restriction effect results from strategically reduced investment in reproduction in favor of somatic maintenance to survive starvation periods until resources become plentiful again. We used experimental evolution to test this "waiting-for-the-good-times" hypothesis, which predicts that selection under sustained dietary restriction will favor increased investment in reproduction at the cost of survival because "good-times" never come. We assayed fecundity and survival of female Drosophila melanogaster fruit flies that had evolved for 50 generations on three different diets varying in protein content-low (classic dietary restriction diet), standard, and high-in a full-factorial design. High-diet females evolved overall increased fecundity but showed reduced survival on low and standard diets. Low-diet females evolved reduced survival on low diet without corresponding increase in reproduction. In general, there was little correspondence between the evolution of survival and fecundity across all dietary regimes. Our results contradict the hypothesis that resource reallocation between fecundity and somatic maintenance underpins life span extension under dietary restriction.

 

PUBLIC RELEASE: 5-APR-2018

Eating less enables lemurs to live longer

CNRS

https://www.eurekalert.org/pub_releases/2018-04/c-ele040418.php

>>>>>>>>>>>>>>>>>>>>>

Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates

Fabien Pifferi, Jérémy Terrien, Julia Marchal, Alexandre Dal-Pan, Fathia Djelti, Isabelle Hardy, Sabine Chahory, Nathalie Cordonnier, Loïc Desquilbet, Murielle Hurion, Alexandre Zahariev, Isabelle Chery, Philippe Zizzari, Martine Perret, Jacques Epelbaum, Stéphane Blanc, Jean-Luc Picq, Marc Dhenain & Fabienne Aujard

Communications Biologyvolume 1, Article number: 30 (2018)

doi:10.1038/s42003-018-0024-8

Ageing, Neural ageing

Received:

30 November 2017

Accepted:

21 February 2018

Published online:

05 April 2018

https://www.nature.com/articles/s42003-018-0024-8

https://www.nature.com/articles/s42003-018-0024-8.pdf

Abstract

The health benefits of chronic caloric restriction resulting in lifespan extension are well established in many short-lived species, but the effects in humans and other primates remain controversial. Here we report the most advanced survival data and the associated follow-up to our knowledge of age-related alterations in a cohort of grey mouse lemurs (Microcebus murinus, lemurid primate) exposed to a chronic moderate (30%) caloric restriction. Compared to control animals, caloric restriction extended lifespan by 50% (from 6.4 to 9.6 years, median survival), reduced aging-associated diseases and preserved loss of brain white matter in several brain regions. However, caloric restriction accelerated loss of grey matter throughout much of the cerebrum. Cognitive and behavioural performances were, however, not modulated by caloric restriction. Thus chronic moderate caloric restriction can extend lifespan and enhance health of a primate, but it affects brain grey matter integrity without affecting cognitive performances.

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Reversing age-associated arterial dysfunction: insight from preclinical models.

Gogulamudi VR, Cai J, Lesniewski LA.

J Appl Physiol (1985). 2018 May 10. doi: 10.1152/japplphysiol.00086.2018. [Epub ahead of print]

PMID: 29745797

Abstract

Cardiovascular diseases (CVDs) remain the leading causes of death in the US, and advancing age is a primary risk factor. Impaired endothelium dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase lifespan and improve age-related phenotypes, including arterial dysfunction. However, the translatability of long term CR to clinical populations is limited, stimulating interest in the pursuit of pharmacological CR mimetics to reproduce the beneficial effects of CR. The energy sensing pathways, mammalian target of rapamycin (mTOR), adenosine monophosphate protein kinase (AMPK), and sirtuin-1 (Sirt-1) have all been implicated in the beneficial effects of CR on longevity and/or physiological function and, as such, have emerged as potential targets for therapeutic intervention as CR mimetics. Although manipulation of each of these pathways has CR-like benefits on arterial function, the magnitude and/or mechanisms can be disparate from that of CR. Nevertheless, targeting these pathways in older individuals may provide some benefits against arterial dysfunction and CVD in older adults. The goal of this review is to provide a brief discussion of the mechanisms and pathways underlying age-associated dysfunction in large arteries, how these are impacted by CR and to present the available evidence suggesting that targeting energy sensing pathways as vascular CR mimetics.

KEYWORDS:

AMPK; Sirt-1; aging; arterial dysfunction; mTOR

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Impact of APOE2allele on lipid profile change after a weight loss program.

Romero-Moraleda B, Cupeiro Coto R, González-Lamuño D, Amigo T, Szendrei B, Rojo-Tirado MÁ, Calderón FJ, Peinado AB.

Nutr Hosp. 2018 Mar 1;0(0):305-311. doi: 10.20960/nh.1278.

PMID: 29756962

http://revista.nutricionhospitalaria.net/index.php/nh/article/view/1278/808

Abstract

BACKGROUND:

apolipoprotein E (ApoE) polymorphism is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease.

OBJECTIVE:

to evaluate the impact of ApoE2allele in lipid plasma levels and the influence of a healthy hypocaloric diet plus a controlled physical activity on the lipid profile, we performed a study in a cohort of overweight and obese healthy subjects (Body Mass Index (BMI) between 25 and 34.9 kg·m-2).

METHODS:

one hundred eighty participants (96 women), aged 18-50 years participated in a 22 weeks weight loss intervention based on same dietary treatment and different controlled exercise programs. All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure). Blood samples were obtained for lipids measurements at the beginning and end of the study.

RESULTS:

after intervention, men of the E2 group showed the greatest decreases in low-density lipoprotein (LDL), triglycerides (TG) and total cholesterol (TC) values (p = 0.039; p = 0.001; p = 0.001; respectively). For high-density lipoprotein (HDL), E2 group had significant differences compared with E4 at pre- (p = 0.020) and post-intervention values (p = 0.024).

CONCLUSION:

our results show great changes in men carrying ApoE2, mainly in TG and TC concentrations after treatment with hypocaloric diet and controlled exercise. Therefore, adding supervised training to nutritional intervention seems to be a good alternative for the reinforcement of the effect of the treatment.

 

Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.

Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM.

Cell Metab. 2018 May 8. pii: S1550-4131(18)30253-5. doi: 10.1016/j.cmet.2018.04.010. [Epub ahead of print]

PMID: 29754952

Abstract

Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5 weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.

KEYWORDS:

blood pressure; circadian rhythms; circadian system; eTRF; early time-restricted feeding; insulin resistance; insulin sensitivity; intermittent fasting; meal timing; prediabetes

 

Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.

Fitzgerald KC, Vizthum D, Henry-Barron B, Schweitzer A, Cassard SD, Kossoff E, Hartman AL, Kapogiannis D, Sullivan P, Baer DJ, Mattson MP, Appel LJ, Mowry EM.

Mult Scler Relat Disord. 2018 May 5;23:33-39. doi: 10.1016/j.msard.2018.05.002. [Epub ahead of print]

PMID: 29753994

Abstract

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [iQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [iQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [iQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.

KEYWORDS:

Dietary intervention; Multiple sclerosis; Weight loss intervention

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Pilot Study Examining the Influence of Potassium Bicarbonate Supplementation on Nitrogen Balance and Whole-Body Ammonia and Urea Turnover Following Short-Term Energy Restriction in Older Men.

Margolis LM, Ceglia L, Rivas DA, Dawson-Hughes B, Fielding RA.

Nutrients. 2018 May 16;10(5). pii: E624. doi: 10.3390/nu10050624.

PMID: 29772642

Abstract

With aging there is a chronic low-grade metabolic-acidosis that may exacerbate negative protein balance during weight loss. The objective of this randomized pilot study was to assess the impact of 90 mmol∙day-1 potassium bicarbonate (KHCO₃) versus a placebo (PLA) on 24-h urinary net acid excretion (NAE), nitrogen balance (NBAL), and whole-body ammonia and urea turnover following short-term diet-induced weight loss. Sixteen (KHCO₃; n = 8, PLA; n = 8) older (64 ± 4 years) overweight (BMI: 28.5 ± 2.1 kg∙day-1) men completed a 35-day controlled feeding study, with a 7-day weight-maintenance phase followed by a 28-day 30% energy-restriction phase. KHCO₃ or PLA supplementation began during energy restriction. NAE, NBAL, and whole-body ammonia and urea turnover (15N-glycine) were measured at the end of the weight-maintenance and energy-restriction phases. Following energy restriction, NAE was -9.8 ± 27.8 mmol∙day-1 in KHCO₃ and 43.9 ± 27.8 mmol∙day-1 in PLA (p < 0.05). No significant group or time differences were observed in NBAL or ammonia and urea turnover. Ammonia synthesis and breakdown tended (p = 0.09) to be higher in KHCO₃ vs. PLA following energy restriction, and NAE was inversely associated (r = -0.522; p < 0.05) with urea synthesis in all subjects. This pilot study suggests some benefit may exist with KHCO₃ supplementation following energy restriction as lower NAE indicated higher urea synthesis.

KEYWORDS:

acid-base; aging; alkaline supplement; weight loss

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Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction.

Heinitz S, Piaggi P, Yang S, Bonfiglio S, Steel J, Krakoff J, Votruba SB.

Int J Obes (Lond). 2018 May 17. doi: 10.1038/s41366-018-0085-2. [Epub ahead of print]

PMID: 29777235

Abstract

BACKGROUND/OBJECTIVES:

Spendthrift vs. thrifty individuals expend more energy and experience greater weight loss during caloric restriction (CR). Adaptive mechanisms in skeletal muscle, adipose tissue, and on hormone level modulate energy expenditure (EE) during weight loss. Metabolic mechanisms underlying the variability in EE during CR are unclear. The present study explored whether during long-term CR (i) gene expression changes in skeletal muscle and adipose tissue relate with the individual EE response and weight loss, and (ii) altered catecholamine and FGF21-concentrations are associated with measures of metabolic adaptation.

SUBJECTS/METHODS:

In a 10-week inpatient study, 24-h EE was measured before and after 6 weeks of 50% CR in 12 subjects using whole-room indirect calorimetry. Weight loss was assessed and repeated hormone measurements performed. Muscle and adipose tissue biopsies were taken before and after CR, and gene expression was assessed (RNA-Seq). Genes showing the most significant changes after CR were tested for association with EE and followed-up for further association with metabolic measures in a separate phenotyping study (n = 103).

RESULTS:

Muscle UCP2 showed the strongest change after CR (log2-fold change = -1.57, false discovery rate = 0.10) and was considered the best gene for exploration of metabolic adaptive processes. A greater decrease in UCP2-expression was associated with less weight loss (P = 0.03, r = 0.77) and relatively lower 24-h EE after CR (P = 0.001, r = -0.96). Post-CR changes in FGF21-plasma concentrations correlated with UCP2-expression change (P = 0.02, r = -0.89) and weight loss (P = 0.003, r = -0.83). In a separate metabolic phenotyping study, muscle UCP2-expression correlated with respiratory quotient and macronutrient oxidation. In adipose tissue, no candidate genes for metabolic exploration were found.

CONCLUSIONS:

Changes in muscle UCP2-expression reflect an inter-individual metabolic response to long-term CR and may influence EE and weight loss via modulation of substrate oxidation.

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Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial.

Sundfør TM, Svendsen M, Tonstad S.

Nutr Metab Cardiovasc Dis. 2018 Mar 29. pii: S0939-4753(18)30100-5. doi: 10.1016/j.numecd.2018.03.009. [Epub ahead of print]

PMID: 29778565

Abstract

BACKGROUND & AIMS:

Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome.

METHODS & RESULTS:

In total 112 participants (men [50%] and women [50%]) aged 21-70 years with BMI 30-45 kg/m2 (mean 35.2 [sD 3.7]) were randomized to intermittent or continuous energy restriction. A 6-month weight-loss phase including 10 visits with dieticians was followed by a 6-month maintenance phase without additional face-to-face counselling. The intermittent energy restriction group was advised to consume 400/600 kcal (female/male) on two non-consecutive days. Based on dietary records both groups reduced energy intake by ∼26-28%. Weight loss was similar among participants in the intermittent and continuous energy restriction groups (8.0 kg [sD 6.5] versus 9.0 kg [sD 7.1]; p = 0.6). There were favorable improvements in waist circumference, blood pressure, triglycerides and HDL-cholesterol with no difference between groups. Weight regain was minimal and similar between the intermittent and continuous energy restriction groups (1.1 kg [sD 3.8] versus 0.4 kg [sD 4.0]; p = 0.6). Intermittent restriction participants reported higher hunger scores than continuous restriction participants on a subjective numeric rating scale (4.7 [sD 2.2] vs 3.6 [sD 2.2]; p = 0.002).

CONCLUSIONS:

Both intermittent and continuous energy restriction resulted in similar weight loss, maintenance and improvements in cardiovascular risk factors after one year. However, feelings of hunger may be more pronounced during intermittent energy restriction.

KEYWORDS:

Cardiometabolic risk factors; Intermittent energy restriction; Metabolic syndrome; Weight loss

 

Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice.

Page MM, Schuster EF, Mudaliar M, Herzyk P, Withers DJ, Selman C.

Aging (Albany NY). 2018 May 20. doi: 10.18632/aging.101446. [Epub ahead of print]

PMID: 29779018

Abstract

Dietary restriction (DR) is the most widely studied non-genetic intervention capable of extending lifespan across multiple taxa. Modulation of genes, primarily within the insulin/insulin-like growth factor signalling (IIS) and the mechanistic target of rapamycin (mTOR) signalling pathways also act to extend lifespan in model organisms. For example, mice lacking insulin receptor substrate-1 (IRS1) are long-lived and protected against several age-associated pathologies. However, it remains unclear how these particular interventions act mechanistically to produce their beneficial effects. Here, we investigated transcriptional responses in wild-type and IRS1 null mice fed an ad libitum diet (WTAL and KOAL) or fed a 30% DR diet (WTDR or KODR). Using an RNAseq approach we noted a high correlation coefficient of differentially expressed genes existed within the same tissue across WTDR and KOAL mice and many metabolic features were shared between these mice. Overall, we report that significant overlap exists in the tissue-specific transcriptional response between long-lived DR mice and IRS1 null mice. However, there was evidence of disconnect between transcriptional signatures and certain phenotypic measures between KOAL and KODR, in that additive effects on body mass were observed but at the transcriptional level DR induced a unique set of genes in these already long-lived mice.

KEYWORDS:

dietary restriction; insulin receptor substrate 1; insulin/IGF-1 signalling; lifespan; transcriptomics

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Nutrition and Inflammation: Are Centenarians Similar to Individuals on Calorie-Restricted Diets?

Franceschi C, Ostan R, Santoro A.

Annu Rev Nutr. 2018 May 31. doi: 10.1146/annurev-nutr-082117-051637. [Epub ahead of print]

PMID: 29852087

sci-hub.org

Abstract

Individuals capable of reaching the extreme limit of human life such as centenarians are characterized by an exceptionally healthy phenotype-that is, a low number of diseases, low blood pressure, optimal metabolic and endocrine parameters, and increased diversity in the gut microbiota-and they are epigenetically younger than their chronological age. We present data suggesting that such a remarkable phenotype is largely similar to that found in adults following a calorie-restricted diet. Interviews with centenarians and historical data on the nutritional and lifestyle habits of Italians during the twentieth century suggest that as children and into adulthood, centenarians lived in an environment that was nonobesogenic, but at the same time the environment did not produce malnutrition. Centenarians appear to be creatures of habit, and we argue that their habit of eating meals at the same time each day favored the maintenance of circadian rhythms, including their sleep cycle. Finally, we argue that centenarians' chronic inflammatory status, which we dubbed inflammaging, is peculiar, likely adaptive, and less detrimental than in younger people.

 

Deep phenotyping in zebrafish reveals genetic and diet-induced adiposity changes that may inform disease risk.

Minchin JEN, Scahill CM, Staudt N, Busch-Nentwich EM, Rawls JF.

J Lipid Res. 2018 May 23. pii: jlr.D084525. doi: 10.1194/jlr.D084525. [Epub ahead of print]

PMID: 29794036

https://sci-hub.hk/

Abstract

The regional distribution of adipose tissues is implicated in a wide range of diseases. For example, proportional increases in visceral adipose tissue increase the risk for insulin resistance, diabetes and cardiovascular disease. Zebrafish offer a tractable model system by which to obtain unbiased and quantitative phenotypic information on regional adiposity, and deep phenotyping can explore complex disease-related adiposity traits. To facilitate deep phenotyping of zebrafish adiposity traits, we used pairwise correlations between 67 adiposity traits to generate stage-specific adiposity profiles that describe changing adiposity patterns and relationships during growth. Linear discriminant analysis classified individual fish according to adiposity profile with 87.5% accuracy. Deep phenotyping of eight previously uncharacterized zebrafish mutants identified neuropilin 2b as a novel gene that alters adipose distribution. When we applied deep phenotyping to identify changes in adiposity during diet manipulations, zebrafish that underwent food restriction and re-feeding had widespread adiposity changes when compared to continuously-fed, equivalently-sized control animals. In particular, internal adipose tissues (e.g., visceral adipose) exhibited a reduced capacity to replenish lipid following food restriction. Together, these results in zebrafish establish a new deep phenotyping technique as an unbiased and quantitative method to help uncover new relationships between genotype, diet and adiposity.

KEYWORDS:

Adipose tissue; Fluorescence microscopy; Lipid droplets; Lipids; Obesity; Zebrafish

 

Interventions to promote cardiometabolic health and slow cardiovascular ageing.

Fontana L.

Nat Rev Cardiol. 2018 May 23. doi: 10.1038/s41569-018-0026-8. [Epub ahead of print] Review.

PMID: 29795242

https://sci-hub.hk/

Abstract

Cardiovascular ageing and the atherosclerotic process begin very early in life, most likely in utero. They progress over decades of exposure to suboptimal or abnormal metabolic and hormonal risk factors, eventually culminating in very common, costly, and mostly preventable target-organ pathologies, including coronary heart disease, stroke, heart failure, aortic aneurysm, peripheral artery disease, and vascular dementia. In this Review, we discuss findings from preclinical and clinical studies showing that calorie restriction (CR), intermittent fasting, and adjusted diurnal rhythm of feeding, with adequate intake of specific macronutrients and micronutrients, are powerful interventions not only for the prevention of cardiovascular disease but also for slowing the accumulation of molecular damage leading to cardiometabolic dysfunction. Furthermore, we discuss the mechanisms through which a number of other nondietary interventions, such as regular physical activity, mindfulness-based stress-reduction exercises, and some CR-mimetic drugs that target pro-ageing pathways, can potentiate the beneficial effects of a healthy diet in promoting cardiometabolic health.

 

Nutritional Regulation of Intestinal Stem Cells.

Alonso S, Yilmaz ÖH.

Annu Rev Nutr. 2018 May 23. doi: 10.1146/annurev-nutr-082117-051644. [Epub ahead of print]

PMID: 29799767

https://sci-hub.hk/

Abstract

Dietary composition and calorie intake are major determinants of health and disease. Calorie restriction promotes metabolic changes that favor tissue regeneration and is arguably the most successful and best-conserved antiaging intervention. Obesity, in contrast, impairs tissue homeostasis and is a major risk factor for the development of diseases including cancer. Stem cells, the central mediators of tissue regeneration, integrate dietary and energy cues via nutrient-sensing pathways to maintain growth or respond to stress. We discuss emerging data on the effects of diet and nutrient-sensing pathways on intestinal stem cells, as well as their potential application in the development of regenerative and therapeutic interventions.

 

Swimming Exercise and Transient Food Deprivation in Caenorhabditis elegans Promote Mitochondrial Maintenance and Protect Against Chemical-Induced Mitotoxicity.

Hartman JH, Smith LL, Gordon KL, Laranjeiro R, Driscoll M, Sherwood DR, Meyer JN.

Sci Rep. 2018 May 29;8(1):8359. doi: 10.1038/s41598-018-26552-9.

PMID: 29844465

https://www.nature.com/articles/s41598-018-26552-9

Abstract

Exercise and caloric restriction improve health, including reducing risk of cardiovascular disease, neurological disease, and cancer. However, molecular mechanisms underlying these protections are poorly understood, partly due to the cost and time investment of mammalian long-term diet and exercise intervention studies. We subjected Caenorhabditis elegans nematodes to a 6-day, twice daily swimming exercise regimen, during which time the animals also experienced brief, transient food deprivation. Accordingly, we included a non-exercise group with the same transient food deprivation, a non-exercise control with ad libitum access to food, and a group that exercised in food-containing medium. Following these regimens, we assessed mitochondrial health and sensitivity to mitochondrial toxicants. Exercise protected against age-related decline in mitochondrial morphology in body-wall muscle. Food deprivation increased organismal basal respiration; however, exercise was the sole intervention that increased spare respiratory capacity and proton leak. We observed increased lifespan in exercised animals compared to both control and transiently food-deprived nematodes. Finally, exercised animals (and to a lesser extent, transiently food-deprived animals) were markedly protected against lethality from acute exposures to the mitotoxicants rotenone and arsenic. Thus, swimming exercise and brief food deprivation provide effective intervention in C. elegans, protecting from age-associated mitochondrial decline and providing resistance to mitotoxicant exposures.

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Intermittent energy restriction for weight loss: Spontaneous reduction of energy intake on unrestricted days.

Harvey J, Howell A, Morris J, Harvie M.

Food Sci Nutr. 2018 Feb 21;6(3):674-680. doi: 10.1002/fsn3.586. eCollection 2018 May.

PMID: 29876119

https://onlinelibrary.wiley.com/doi/pdf/10.1002/fsn3.586

Abstract

There is increasing interest for the use of intermittent energy restriction (IER) in weight management. However, there are concerns that IER could result in 'rebound' overconsumption of energy on unrestricted days. We studied self-reported food records from participants in two trials of IER versus continuous energy restriction (Study 1; 44 women on IER for 6 months and Study 2; 72 women on two types of IER for 4 months). Energy intake was assessed on restricted and unrestricted days immediately before and after restricted days and on other unrestricted days. We assessed consistency of days of the week chosen as restricted days, and whether this was associated with greater weight loss. Reported energy intake was reduced on unrestricted days in Study 1 and 2 and was 19% lower compared with the allocated isoenergetic diet, and respectively 21% and 29% lower than their baseline reported daily intakes. Energy intake appeared to be similarly reduced the day immediately before and after restricted days and on other unrestricted days. Seventy percent of women in Study 1 and 79% in Study 2 undertook consistent days of restriction each week (>50% of restricted days on the same 2 days each week). When studies were combined percentage weight loss at 3 months was -5.8 (-6.7 to -4.7) % in the consistent group and -7.4 (-8.7 to -6.2) % in the non-consistent group (p = .09). Food records from patients undertaking IER suggest a spontaneous reduction in energy intake below their baseline reported intakes and the prescribed isoenergetic diet during all unrestricted days including the days immediately before and after restricted days which contributes to the weight loss success with these diets. Consistency of restricted days was not associated with weight loss success. These findings need to be confirmed in larger groups of patients ideally using objective measures of energy balance.

KEYWORDS:

energy intake; energy restriction; food records; intermittent; weight loss

 

Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.

Cignarella F, Cantoni C, Ghezzi L, Salter A, Dorsett Y, Chen L, Phillips D, Weinstock GM, Fontana L, Cross AH, Zhou Y, Piccio L.

Cell Metab. 2018 Jun 5;27(6):1222-1235.e6. doi: 10.1016/j.cmet.2018.05.006.

PMID: 29874567

Abstract

Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.

KEYWORDS:

diet; experimental autoimmune encephalomyelitis; gut microbiota; intermittent fasting; multiple sclerosis

 

Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report.

Headland ML, Clifton PM, Keogh JB.

Int J Environ Res Public Health. 2018 Jun 4;15(6). pii: E1166. doi: 10.3390/ijerph15061166.

PMID: 29867034

http://www.mdpi.com/1660-4601/15/6/1166/htm

Abstract

Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

KEYWORDS:

endothelial function; flow mediated dilatation; intermittent energy restriction

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The effect of different levels of dietary restriction on glucose homeostasis and metabolic memory.

Matyi S, Jackson J, Garrett K, Deepa SS, Unnikrishnan A.

Geroscience. 2018 Apr;40(2):139-149. doi: 10.1007/s11357-018-0011-5. Epub 2018 Feb 17.

PMID: 29455275 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964050/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964050/pdf/11357_2018_Article_11.pdf

Abstract

Over the past 50 years, dietary restriction (DR) has been shown to extend the life span of a wide variety of organisms. A hallmark feature of DR is improved glucose homeostasis resulting in increased glucose tolerance and insulin sensitivity of animals ranging from rodents to humans. In this study, we demonstrate the early effects of varying levels of DR on glucose tolerance. Within 10 days of 40% DR, glucose tolerance was significantly improved and by 120 days; 10 and 20% DR also showed enhanced glucose tolerance. All three levels of DR showed reduced adiposity, increased expression of genes involved in fat turnover, and a reduction in the expression for markers of inflammation. Studies have shown that mice fed a DR diet retained metabolic memory in terms of improved glucose tolerance even after DR is discontinued. We show that 40% DR not only has an early effect on glucose tolerance but also maintained it after DR was discontinued for 2 months. Therefore, improvement in glucose tolerance is brought about by all three levels of DR but the metabolic memory is not dose responsive.

KEYWORDS:

Adiposity; Dietary restriction; Gene expression; Glucose tolerance; Metabolic memory

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Biological Effects of Dietary Restriction

Editors

Lawrence Fishbein

Conference proceedings

Part of the ILSI Monographs book series (ILSI MONOGRAPHS)

https://link.springer.com/book/10.1007/978-3-642-58181-6

https://link.springer.com/book/10.1007/978-3-642-58181-6?page=2#toc

 

Biological Effects of Dietary Restriction pp 245-263

Chronic Caloric Restriction in Old Female Mice: Changes in the Circadian Rhythms of Physiological and Behavioral Variables

P. H. DuffyR. J. FeuersJ. E. A. LeakeyR. W. Hart

Abstract

One of the most frequently reported observations in the gerontological literature is the significant increase in life span (Sacher 1977; McCay et al. 1935) and the prevention or delayed onset of various types of chronic diseases (Walford et al. 1974; Maeda et al. 1985) associated with chronic caloric restriction (CR). CR has also been shown to be effective in inhibiting various types of spontaneous tumors (Sarkar et al. 1985) and chemically induced lesions (Ruggeri et al. 1987; Kritchevsky et al. 1984) in rats and mice. However, little is known about the primary mechanisms by which CR interacts with environmental factors to alter the timing of the biological clock. One hypothesis that may account for the slowing down of age-related physiological and disease processes is that the synchronization of organisms to their surroundings is controlled or modified by qualitative or quantitative changes in nutritional parameters and that changes in 24-h (circadian) rhythms that are a direct result of CR may ultimately alter primary mechanisms of aging. Several studies in which total calories were restricted to 76% of ad libitum (AL) by limiting access to food to a few hours daily (single meal feeding) (Nelson et al. 1975; Philippens et al. 1977) or when intake was decreased by reducing the total weight of the food pellets fed to the caloric restricted group to 60% of the AL level (Duffy et al. 1989a; McCarter et al. 1985) have reported significant alterations in the circadian rhythms of various physiological and biochemical parameters. However, in other studies, no significant difference in longevity was found in CR mice fed a single meal during the early light phase, a single meal during the dark phase, or fed multiple meals (six times) during the dark phase (Nelson and Halberg 1986a). While CR in itself was found to prolong life, the added imposition of frequent photoperiod schedule shifting had no statistically significant effect on mean survival time, regardless of whether the meal schedule reinforced or opposed shifts in the photoperiod (Nelson and Halberg 1986b). This may mean that varying the dietary regimen may have no effect on longevity if the total amount of food consumed is maintained at a constant restricted calorie level.

Keywords

Circadian Rhythm Water Consumption Respiratory Quotient Caloric Restriction Group Caloric Restriction Mouse

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Hi Mechanism, Google and thanks for pointing out a point I missed.

 

Do-It-Yourself Calorie Restriction: The Risks of Simplistically Translating Findings in Animal Models to Humans.

Le Bourg E, Redman LM.

Bioessays. 2018 Jun 13:e1800087. doi: 10.1002/bies.201800087. [Epub ahead of print] No abstract available.

PMID: 29897135

https://sci-hub.tw/

Calorie restriction (CR) experiments are now being carried

out in humans, and the latest studies are attracting

considerable attention from the mass-media. Here we discuss

and qualify CR in humans, with the aim of preventing

misinterpretation or inappropriate extrapolation of results

from animal models of CR. Essentially we wish to curb

uninformed attempts by the general public to practice CR on

their own, because it can be risky, particularly in old age.

Calorie restriction (a reduced calorie intake without causing

malnutrition) has been studied in rodents for decades and in

rhesus macaques for around 30 years.[1,2] While not all

species live longer when calorie- or diet-restricted,[3] it is often

observed that CR increases lifespan in rodents, and there is a

debate on the lifespan effect in macaques. CR experiments

such as CALERIE, a randomized controlled trial (e.g.,

reference [4]), are now being carried out in humans. With

each new publication on the effect of CR in humans, wide

coverage in newspapers, e-press, and TV occurs worldwide.

Unfortunately, the headlines of these reports, if not the text

itself, often propagate an over-enthusiastic view of results.

For instance, after the recent article from the CALERIE trial[4]

headlines stated “Cut calories by 15% to stay young, study

says” (https://edition.cnn.com/2018/03/22/health/calorierestriction-longer-life-study/index.html)

or “You may live

longer by severely restricting calories, scientists say”

(https://www.npr.org/sections/thesalt/2018/04/02/

598295025/scientists-say-you-may-live-longer-by-severelyrestricting-calories).

The two authors of the present article do

not share the same view regarding the possible CR effect in

humans. Specifically, the first author thinks that CR would

not increase lifespan,[5] while the second author “estimated

that a 5-year life extension could be induced by 20% CR

starting at age 25 and sustained for 52 years”.

[6] However,

both authors agree that it is important to express some

statements about CR in humans, to avoid any misinterpretation

or inappropriate extrapolation of results, and more

importantly, to curb attempts by most people to practice CR

on their own.

1- CR in human subjects is studied in clinical trials under the

close supervision of trained physicians and behavioral

psychologists. Routine medical exams monitor body weight,

bone mass, hematocrit, blood potassium concentration,

mood (i.e., for sign of depression), eating behaviors (i.e.,

eating disorders), and other variables such as menstrual cycle

activity in women. CR should therefore not be thought of as

being a “ready-to-use” therapy to delay aging and increase

lifespan: it is too early to assume that it will soon become a

part of our therapeutic arsenal.

2- While both authors hopethat CR human studiesmay give riseto

a public health program for fighting secondary causes of aging

known to decrease lifespan (i.e., chronic diseases), there is a

debate regarding effects of CR on aging and lifespan for nonobese

people. Currently, no study has shown that CR can

increaselifespan and/or delay agingin human beings.However,

it is unlikely that randomized CR trials, which would need to

study participants until death, will ever be conducted.

3- CR studies in humans have reported improvements in

quality of life and changes in many health parameters that are

often predictive of age-related or metabolic diseases (e.g.,

reference [4,7]). These studies have also reported adverse

events, such as “bone loss at clinically important sites of

osteoporotic fractures,”

[8] and minor disorders that are more

frequent in non-overweight subjects than in overweight

ones.[9] No serious adverse event has been reported in

subjects participating in CR studies, such as CALERIE; but it

should be noted that it could be due to the close medical

monitoring throughout the study.

4- There is a high prevalence of malnutrition in elderly patients,

and malnutrition is predictive of a higher mortality during

hospitalization.[10] Therefore, because elderly people are often

undernourished, they should be advised to not self-practice CR

in the hope of living longer and delaying aging, because they

may risk their health, if not life. Indeed, the risk for elderly

people is often not to eating too much, but eating too little.

5- People with a low body-mass index (BMI, say below 21 kg m^2)

should also be cautioned against practicing CR, as they could

soon become underweight, which is a risk factor for various

health concerns. Only people in the 22–30 kg m^2 BMI range

have been studied in the CALERIE trials, and the level of CR

was lessened or temporarily discontinued if BMI fell below

18.5 kg m^2 (e.g., 60 kg and 1.80 m). SubjectsinCALERIEwere

also provided a multi-vitamin and mineral supplement and

additional calcium supplements, and received routine blood

chemistry monitoring to ensure that the restricted diet was still

sufficiently nutritionally rich—a fundamental principle in CR

strategies for slowing aging.

6- An easy, currently available, method to decrease the risk for

metabolic diseases is to adopt a well-balanced diet and to

remain weight-stable with increasing age. Having a wellbalanced

diet coupled with regular physical activity does not

involve any risk and is advocated for optimal health. In any

case, people wanting to achieve the long-term weight loss

results (9 kg) reported by the CALERIE studies should rely

on the advice and monitoring of their physician.

7- Finally, at whatever age or BMI people find themselves, they

should not try to practice CR on their own because, for the

time being, CR has only been studied in clinical trials for

relatively short periods of time (2 years) and with close

monitoring by trained physicians and psychologists. CR with

the aim of delaying aging and increasing longevity is not an

approved treatment for self-administration.

 

[Caloric restriction and memory during aging].

Marti-Nicolovius M, Arevalo-Garcia R.

Rev Neurol. 2018 Jun 16;66(12):415-422. Review. Spanish.

PMID: 29897609

Abstract in English, Spanish

INTRODUCTION:

To understand the underlying brain mechanisms involved in the aging process and mental deterioration could be key to the development of behavioral patterns that guarantee reaching advanced ages with the highest possible quality of life and reduce the cognitive loss associated with senescence.

AIM:

To describe and analyze different animal and human studies that demonstrate that a caloric restriction diet may rescue cerebral aging and the cognitive decline associated to aging.

DEVELOPMENT:

For more than 100 years it has been known that caloric restriction extends life span in many laboratory animal. This effect seems to derive from the reduction of age-related symptoms, such as obesity, the onset of cancerous tumors and some metabolic diseases. However, while the consequences of caloric restriction on health are well-established, their ability to reverse age-dependent memory deficits remains a controversial issue. The analyses of the effects of caloric restriction on different animals provides progress for the understanding of its beneficial effects on the neurobiology of cognitive processes during aging.

CONCLUSIONS:

Caloric restriction attenuates the normal or pathological aging of the brain and reduces age-related memory problems. Dietary intervention could become a very effective method to promote a better quality of life and prevent the age-related cognitive deficits.

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