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Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins.

Charles KN, Li MD, Engin F, Arruda AP, Inouye K, Hotamisligil GS.

Cell Rep. 2017 Oct 10;21(2):393-402. doi: 10.1016/j.celrep.2017.09.051.

PMID: 29020626

http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31341-4

http://www.cell.com/cell-reports/pdf/S2211-1247(17)31341-4.pdf

Abstract

Deterioration of metabolic health is a hallmark of aging and generally assumed to be detrimental to longevity. Exposure to a high-calorie diet impairs metabolism and accelerates aging; conversely, calorie restriction (CR) prevents age-related metabolic diseases and extends lifespan. However, it is unclear whether preservation of metabolic health is sufficient to extend lifespan. We utilized a genetic mouse model lacking Fabp4/5 that confers protection against metabolic diseases and shares molecular and lipidomic features with CR to address this question. Fabp-deficient mice exhibit extended metabolic healthspan, with protection against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease. Surprisingly, however, Fabp-deficient mice did not exhibit any extension of lifespan. These data indicate that extension of metabolic healthspan in the absence of CR can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways, at least in laboratory mice.

KEYWORDS:

aging; calorie restriction; de novo lipogenesis; diabetes; fatty acid binding protein; inflammation; metabolic health; metaflammation; obesity

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Recent Advances in the Systems Biology of Aging.

Promislow DEL, McCormick MA.

Antioxid Redox Signal. 2017 Oct 12. doi: 10.1089/ars.2017.7367. [Epub ahead of print]

PMID: 29020802

Abstract

<b><i>Significance</i></b>: Reductionist studies have contributed greatly to our understanding of the basic biology of aging in recent years but we still do not understand fundamental mechanisms for many identified drugs and pathways. Use of systems approaches will help us move forward in our understanding of aging. <b><i>Recent Advances</i></b>: Recent work described here has illustrated the power of systems biology to inform our understanding of aging through the study of 1) diet restriction; 2) neurodegenerative disease; and 3) biomarkers of aging. <b><i>Critical Issues</i></b>: Although we do not understand all of the individual genes and pathways that affect aging, as we continue to uncover more of them, we have now also begun to synthesize existing data using systems-level approaches, often to great effect. The three examples noted here all benefit from computational approaches that were unknown a few years ago, and from biological insights gleaned from multiple model systems, from aging labs as well as many other areas of biology. <b><i>Future Directions</i></b>: Many new technologies, such as single-cell sequencing, advances in epigenetics beyond the methylome (specifically, ATAC-seq), and multi-omic network studies, will increase the reach of systems biologists. This suggests that approaches similar to those described here will continue to lead to striking findings, and to interventions that may allow us to delay some of the many age-associated diseases in humans; perhaps sooner that we expect.

 

Nutritional geometry of paternal effects on embryo mortality.

Polak M, Simmons LW, Benoit JB, Ruohonen K, Simpson SJ, Solon-Biet SM.

Proc Biol Sci. 2017 Oct 11;284(1864). pii: 20171492. doi: 10.1098/rspb.2017.1492.

PMID: 29021174

Abstract

Well-established causal links exist between maternal nutritional deficits and embryo health and viability. By contrast, environmental effects operating through the father that could influence embryo mortality have seldom been examined. Yet, ejaculates can require non-trivial resource allocation, and seminal plasma components are increasingly recognized to exert wide-ranging effects on females and offspring, so paternal dietary effects on the embryo should be expected. We test for effects of varying levels of protein (P), carbohydrate © and caloric load in adult male diet on embryo mortality in Drosophila melanogaster We demonstrate that macronutrient balance and caloric restriction exert significant effects, and that nutritional effects are more impactful when a prior mating has occurred. Once-mated males produced embryos with marginally elevated mortality under high-caloric densities and a 1 : 8 P : C ratio. In contrast, embryos produced by twice-mated males were significantly more likely to die under male caloric restriction, an outcome that may have resulted from shifts in ejaculate quality and/or epigenetic paternal effects. Body nutrient reserves were strongly and predictably altered by diet, and body condition, in turn, was negatively related to embryo mortality. Thus, sire nutritional history and resultant shifts in metabolic state predict embryo viability and post-fertilization fitness outcomes.

KEYWORDS:

ejaculate quality; embryo mortality; macronutrients; paternal diet

 

Combined Salt and Caloric Restrictions: Potential Adverse Outcomes.

Homma T, Homma M, Huang Y, Mayurasakorn K, Rodi NM, Hamid AAA, Hurwitz S, Yao T, Adler GK, Pojoga LH, Williams GH, Romero JR.

J Am Heart Assoc. 2017 Oct 11;6(10). pii: e005374. doi: 10.1161/JAHA.116.005374.

PMID: 29021272

http://jaha.ahajournals.org/content/6/10/e005374

Abstract

BACKGROUND:

We hypothesized that caloric restriction (CR) and salt restriction (ResS) would have similar effects on reducing cardiovascular risk markers and that combining CR and ResS would be synergistic in modulating these markers.

METHODS AND RESULTS:

To test our hypothesis, rats were randomized into 2 groups: ad libitum liberal salt diet (ad libitum/high-sodium, 1.6% sodium) or ResS diet (ad libitum/ResS, 0.03% sodium). CR was initiated in half of the rats in each group by reducing caloric intake to 60% while maintaining sodium intake constant (CR/high-sodium, 2.7% sodium or CR/ResS, 0.05% sodium) for 4 weeks. CR in rats on a high-sodium diet improved metabolic parameters, renal transforming growth factor-β and collagen-1α1 and increased plasma adiponectin and renal visfatin and NAD+ protein levels. Although CR produced some beneficial cardiovascular effects (increased sodium excretion and reduced blood pressure), it also was associated with potentially adverse cardiovascular effects. Adrenal zona glomerulosa cell responsiveness and aldosterone levels and activation were inappropriately increased for the volume state of the rodent. Like CR on HS, CR on a ResS diet also produced relative increased zona glomerulosa responsiveness and an increased blood pressure with no improvement in metabolic parameters.

CONCLUSIONS:

These results suggest that combining CR and ResS may decrease the beneficial effects of each alone. Furthermore, CR, regardless of dietary salt intake, inappropriately activates aldosterone production. Thus, caution should be used in combining ResS and CR because the combination may lead to increased cardiovascular risk.

KEYWORDS:

aldosterone; blood pressure; caloric restriction; high blood pressure; hypertension; insulin action; insulin resistance; mineralocorticoids; salt intake

 

Activation of Autophagy Ameliorates Cardiomyopathy in Mybpc3-Targeted Knockin Mice.

Singh SR, Zech ATL, Geertz B, Reischmann-Düsener S, Osinska H, Prondzynski M, Krämer E, Meng Q, Redwood C, van der Velden J, Robbins J, Schlossarek S, Carrier L.

Circ Heart Fail. 2017 Oct;10(10). pii: e004140. doi: 10.1161/CIRCHEARTFAILURE.117.004140.

PMID: 29021349

Abstract

BACKGROUND:

Alterations in autophagy have been reported in hypertrophic cardiomyopathy (HCM) caused by Danon disease, Vici syndrome, or LEOPARD syndrome, but not in HCM caused by mutations in genes encoding sarcomeric proteins, which account for most of HCM cases. MYBPC3, encoding cMyBP-C (cardiac myosin-binding protein C), is the most frequently mutated HCM gene.

METHODS AND RESULTS:

We evaluated autophagy in patients with HCM carrying MYBPC3 mutations and in a Mybpc3-targeted knockin HCM mouse model, as well as the effect of autophagy modulators on the development of cardiomyopathy in knockin mice. Microtubule-associated protein 1 light chain 3 (LC3)-II protein levels were higher in HCM septal myectomies than in nonfailing control hearts and in 60-week-old knockin than in wild-type mouse hearts. In contrast to wild-type, autophagic flux was blunted and associated with accumulation of residual bodies and glycogen in hearts of 60-week-old knockin mice. We found that Akt-mTORC1 (mammalian target of rapamycin complex 1) signaling was increased, and treatment with 2.24 mg/kg·d rapamycin or 40% caloric restriction for 9 weeks partially rescued cardiomyopathy or heart failure and restored autophagic flux in knockin mice.

CONCLUSIONS:

Altogether, we found that (1) autophagy is altered in patients with HCM carrying MYBPC3 mutations, (2) autophagy is impaired in Mybpc3-targeted knockin mice, and (3) activation of autophagy ameliorated the cardiac disease phenotype in this mouse model. We propose that activation of autophagy might be an attractive option alone or in combination with another therapy to rescue HCM caused by MYBPC3 mutations.

KEYWORDS:

autophagy; caloric restriction; cardiomyopathy; hypertrophy; rapamycin

 

Effect of Antioxidants on Testicular iNOS and eNOS after High-Fat Diet in Rat.

Sohrabi M, Hosseini M, Inan S, Alizadeh Z, Vahabian M, Vahidinia AA, Lahoutian H.

Pak J Biol Sci. 2017;20(6):289-297. doi: 10.3923/pjbs.2017.289.297.

PMID: 29023053

http://scialert.net/fulltext/?doi=pjbs.2017.289.297&org=11

http://scialert.net/qredirect.php?doi=pjbs.2017.289.297&linkid=pdf

Abstract

BACKGROUND AND OBJECTIVE:

Spermatogenesis is a process by which germ cells produce spermatozoa and can be disturbed at every level. Nitric Oxide Synthases (NOS), implicate in interactions with Oxidative Stress (OS) which is one of the main factors in the etiology of male infertility. The High Fat Diet (HFD) is a major factor of obesity which in turn is important for enhancing OS. Antioxidants and garlic could attenuate or reverse effects of HFD. The aim of the study was to investigate the effects of dietary antioxidants and garlic on testicular inducible NOS (iNOS) and endothelial NOS (eNOS) in Wistar albino rats fed on HFD.

MATERIALS AND METHODS:

Groups (each n = 8) were: SD (100% access to standard diet), F-HFD, (100% access to HFD) and R-HFD (70% access to HFD), F-HFD +antioxidants, F-HFD+garlic and R-HFD+antioxidants. The HFD consisted of a 60% fatty diet in 3 forms: Without antioxidants, with antioxidants and with garlic. The testicular iNOS and eNOS were studied by immunohistochemical (IHC) method. Also used ANOVA, repeated measures ANOVA, t-tests and Tukey's test (where necessary) to analyze the data (p<0.05).

RESULTS:

The iNOS increased in the F-HFD and R-HFD+antioxidants groups. The eNOS increased in R-HFD,F-HFD and F-HFD+garlic groups. The H-E evaluation in R-HFD group showed a decrease in spermatogenesis score count and seminiferous tubules diameters (μm) in comparison with the SD and F-HFD groups. R-HFD+antioxidants group had lower score than F-HFD+antioxidants and F-HFD+garlic groups.

CONCLUSION:

Restricted fat diet consumption causes increase in weight and impairs spermatogenesis. Results of this study reveal that adding the antioxidants can't improve histological changes of testis. The iNOS expression in seminiferous tubules in restricted fat diet along with antioxidants, suggest a potential role of iNOS in spermatogenesis and male infertility.

KEYWORDS:

Inducible nitric oxide synthase; Obesity; antioxidants; endothelial nitric oxide synthase; immunohistochemistry; infertility; testis

 

Menstrual Disruption with Exercise is not Linked to an Energy Availability Threshold.

Lieberman JL, De Souza MJ, Wagstaff DA, Williams NI.

Med Sci Sports Exerc. 2017 Oct 10. doi: 10.1249/MSS.0000000000001451. [Epub ahead of print]

PMID: 29023359

Abstract

INTRODUCTION:

Chronic reductions in energy availability (EA) suppress reproductive function. A particular calculation of EA quantifies the dietary energy remaining after exercise for all physiological functions. Reductions in LH pulse frequency have been demonstrated when EA using this calculation is < 30 kcal/ kg ffm·d.

PURPOSE:

We determined whether menstrual disturbances (MD) are induced when EA is < 30 kcal/ kg ffm·d.

METHODS:

Thirty-five sedentary, ovulatory women 18-24 yr (weight= 59.0 ± 0.8 kg, BMI= 21.8 ± 0.4 kg·m) completed a diet and exercise intervention over three menstrual cycles. Participants were randomized to groups that varied in the magnitude of negative energy balance created by the combination of exercise and energy restriction. MD were determined using daily urinary estrone-1-glucuronide (E1G) and pregnanediol glucuronide (PdG), mid-cycle LH, and menstrual calendars. In a secondary analysis, we calculated EA from energy balance data and tested the association of EA with menstrual disturbances.

RESULTS:

A generalized linear mixed-effects model showed that the likelihood of a MD decreased by 9% for each unit increase in EA (odds ratio 0.91, 0.84 - 0.98, 95% CI, P=0.010). No specific value of EA emerged as a threshold below which MD were induced. When participants were partitioned into EA tertile groups (Low EA =23.4-34.1; n=11, Moderate EA =34.9-40.7; n=12, and High EA =41.2-50.1; n=12 (kcal/ kg ffm·d)), E1G (p<0.001), PdG (p<0.001), and luteal phase length (p=0.031) decreased significantly, independent of tertile.

CONCLUSION:

These findings do not support that a threshold of EA exists below which MD are induced but do suggest that MD increase linearly as EA decreases. MD can likely be prevented by monitoring EA using a simplified assessment of metabolic status.

 

Modulation of Human Subcutaneous Adipose Tissue microRNA Profile Associated with Changes in Adiposity-Related Parameters.

Giardina S, Hernández-Alonso P, Salas-Salvadó J, Rabassa-Soler A, Bulló M.

Mol Nutr Food Res. 2017 Oct 10. doi: 10.1002/mnfr.201700594. [Epub ahead of print]

PMID: 29024341

Abstract

SCOPE:

To analyze the effect of three calorie-restricted diets with different amount and quality of carbohydrates on subcutaneous adipose tissue (SAT) miRNA profile.

METHODS AND RESULTS:

6-month, parallel, randomized trial conducted on overweight and obese subjects randomized to: 1) low glycemic index diet (LGI), 2) high glycemic index diet (HGI), and 3) low-fat (LF). The genome-wide SAT miRNA profile was assessed in 8 randomly selected participants and the most relevant changing miRNAs (n = 13) were validated in 48 subjects. None of the miRNAs showed significant changes between the intervention groups. However, changes in some of them correlated with changes in biochemical and anthropometric variables. Stratifying our population according to tertiles of percentage change in body weight, we observed a significant down-regulation of miR-210 in those subjects in Tertile 1 compared to Tertile 3. When our population was stratified by tertiles of waist circumference, miR-132, miR-29a, miR-34a and miR-378 were found to be significantly down-regulated, in T2 compared to T3. Furthermore, when stratified by tertiles of fat mass, we also observed the significant down-regulation of miR-132 in T1.

CONCLUSION:

The macronutrient composition of a calorie-restricted diet does not affect the expression of the miRNAs analyzed, while changes in adiposity play a primary regulatory role.

KEYWORDS:

carbohydrates; diet; high-throughput; obesity; post-transcriptional regulation

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A Metabolomic Signature of Acute Caloric Restriction.

Collet TH, Sonoyama T, Henning E, Keogh JM, Ingram B, Kelway S, Guo L, Farooqi IS.

J Clin Endocrinol Metab. 2017 Sep 28. doi: 10.1210/jc.2017-01020. [Epub ahead of print]

PMID: 29029202

Abstract

CONTEXT:

The experimental paradigm of acute caloric restriction followed by refeeding can be used to study the homeostatic mechanisms that regulate energy homeostasis, which are relevant to understanding the adaptive response to weight loss.

OBJECTIVE:

Metabolomics, the measurement of hundreds of small molecule metabolites, their precursors, derivatives, and degradation products, has emerged as a useful tool for the study of physiology and disease and was used here to study the metabolic response to acute caloric restriction.

PARTICIPANTS, DESIGN AND SETTING:

We used four ultra high performance liquid chromatography-tandem mass spectrometry methods to characterize changes in carbohydrates, lipids, amino acids and steroids in eight normal weight men at baseline, after 48 hours of caloric restriction (CR; 10% of energy requirements) and after 48 hours of ad libitum refeeding in a tightly-controlled environment.

RESULTS:

We identified a distinct metabolomic signature associated with acute CR characterized by the expected switch from carbohydrate to fat utilization with increased lipolysis and beta-fatty acid oxidation. We found an increase in omega-fatty acid oxidation and levels of endocannabinoids which are known to promote food intake. These changes were reversed with refeeding. Several plasmalogen phosphatidylethanolamines (endogenous anti-oxidants) significantly decreased with CR (all p≤0.0007). Additionally, acute CR was associated with an increase in the branched chain amino acids (all p≤1.4x10-7) and dehydroepiandrosterone sulfate (p=0.0006).

CONCLUSIONS:

We identified a distinct metabolomic signature associated with acute CR. Further studies are needed to characterise the mechanisms that mediate these changes and their potential contribution to the adaptive response to dietary restriction.

 

Effects of obesity, energy restriction and neutering on the faecal microbiota of cats.

Fischer MM, Kessler AM, Kieffer DA, Knotts TA, Kim K, Wei A, Ramsey JJ, Fascetti AJ.

Br J Nutr. 2017 Oct;118(7):513-524. doi: 10.1017/S0007114517002379. Epub 2017 Sep 29.

PMID: 28958218

http://sci-hub.cc/10.1017/S0007114517002379

Abstract

Surveys report that 25-57 % of cats are overweight or obese. The most evinced cause is neutering. Weight loss often fails; thus, new strategies are needed. Obesity has been associated with altered gut bacterial populations and increases in microbial dietary energy extraction, body weight and adiposity. This study aimed to determine whether alterations in intestinal bacteria were associated with obesity, energy restriction and neutering by characterising faecal microbiota using 16S rRNA gene sequencing in eight lean intact, eight lean neutered and eight obese neutered cats before and after 6 weeks of energy restriction. Lean neutered cats had a bacterial profile similar to obese rodents and humans, with a greater abundance (P<0·05) of Firmicutes and lower abundance (P<0·05) of Bacteroidetes compared with the other groups. The greater abundance of Firmicutes in lean neutered cats was due to a bloom in Peptostreptococcaceae. Obese cats had an 18 % reduction in fat mass after energy restriction (P<0·05). Energy reduction was concurrent with significant shifts in two low-abundance bacterial genera and trends in four additional genera. The greatest change was a reduction in the Firmicutes genus, Sarcina, from 4·54 to 0·65 % abundance after energy restriction. The short duration of energy restriction may explain why few bacterial changes were observed in the obese cats. Additional work is needed to understand how neutering, obesity and weight loss are related to changes in feline microbiota and how these microbial shifts affect host physiology.

KEYWORDS:

BW body weight; D2O deuterium oxide; FM fat mass; PLS-DA partial least squares-discriminant analysis; Energy restriction; Faecal microbiota; Feline nutrition; Neutered cats; Obesity

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A comparative study of anti-aging properties and mechanism: resveratrol and caloric restriction.

Li J, Zhang CX, Liu YM, Chen KL, Chen G.

Oncotarget. 2017 Aug 9;8(39):65717-65729. doi: 10.18632/oncotarget.20084. eCollection 2017 Sep 12.

PMID: 29029466

Abstract

Resveratrol and caloric restriction (CR) are the powerful therapeutic options for anti-aging. Here, their comparative effect on longevity-associated gene silencing information regulator (SIRT1) were evaluated in vitro and in vivo. IMR-90 cells treated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were applied to establish a cellular senescence model, and rats treated with D-galactose (D-gal) were used as an aging animal model. Resveratrol and CR exhibited similar anti-aging activities, evidenced by inhibiting senescence and apoptosis, and restoring cognitive impairment and oxidative damage. Moreover, they could up-regulate telomerase (TE) activity, increase expressions of SIRT1, forkhead box 3a (Foxo3a), active regulator of SIRT1 (AROS) and Hu antigen R (HuR ), but decrease p53 and deleted in breast cancer 1 (DBC1) levels. However, 10 μM resveratrol in vitro and the high dose group in vivo showed relatively stronger activities of anti-aging and stimulating SIRT1 level than CR. In conclusion, resveratrol and CR showed similar anti-aging activities on SIRT1 signaling, implicating the potential of resveratrol as a CR mimetic.

KEYWORDS:

SIRT1; aging; caloric restriction; resveratrol

Abstract

Resveratrol and caloric restriction (CR) are the powerful therapeutic options for anti-aging. Here, their comparative effect on longevity-associated gene silencing information regulator (SIRT1) were evaluated in vitro and in vivo. IMR-90 cells treated with 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were applied to establish a cellular senescence model, and rats treated with D-galactose (D-gal) were used as an aging animal model. Resveratrol and CR exhibited similar anti-aging activities, evidenced by inhibiting senescence and apoptosis, and restoring cognitive impairment and oxidative damage. Moreover, they could up-regulate telomerase (TE) activity, increase expressions of SIRT1, forkhead box 3a (Foxo3a), active regulator of SIRT1 (AROS) and Hu antigen R (HuR ), but decrease p53 and deleted in breast cancer 1 (DBC1) levels. However, 10 μM resveratrol in vitro and the high dose group in vivo showed relatively stronger activities of anti-aging and stimulating SIRT1 level than CR. In conclusion, resveratrol and CR showed similar anti-aging activities on SIRT1 signaling, implicating the potential of resveratrol as a CR mimetic.

KEYWORDS:

SIRT1; aging; caloric restriction; resveratrol

 

Beneficial effects of dietary restriction in aging brain.

Hadem IKH, Majaw T, Kharbuli B, Sharma R.

J Chem Neuroanat. 2017 Oct 11. pii: S0891-0618(17)30082-0. doi: 10.1016/j.jchemneu.2017.10.001. [Epub ahead of print] Review.

PMID: 29031555

https://sci-hub.cc/http://linkinghub.elsevier.com/retrieve/pii/S0891061817300820

Abstract

Aging is a multifactorial complex process that leads to the deterioration of biological functions wherein its underlying mechanism is not fully elucidated. It affects the organism at the molecular and cellular level that contributes to the deterioration of structural integrity of the organs. The central nervous system is the most vulnerable organ affected by aging and its effect is highly heterogeneous. Aging causes alteration in the structure, metabolism and physiology of the brain leading to impaired cognitive and motor-neural functions. Dietary restriction (DR), a robust mechanism that extends lifespan in various organisms, ameliorates brain aging by reducing oxidative stress, improving mitochondrial function, activating anti-inflammatory responses, promoting neurogenesis and increasing synaptic plasticity. It also protects and prevents age-related structural changes. DR alleviates many age-associated diseases including neurodegeneration and improves cognitive functions. DR inhibits/activates nutrient signaling cascades such as insulin/IGF-1, mTOR, AMPK and sirtuins. Because of its sensitivity to energy status and hormones, AMPK is considered as the global nutrient sensor. This review will present an elucidative potential role of dietary restriction in the prevention of phenotypic features during aging in brain and its diverse mechanisms.

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Effects of the dietary approaches to stop hypertension diet, exercise, and caloric restriction on neurocognition in overweight adults with high blood pressure.

Smith PJ, Blumenthal JA, Babyak MA, Craighead L, Welsh-Bohmer KA, Browndyke JN, Strauman TA, Sherwood A.

Hypertension. 2010 Jun;55(6):1331-8. doi: 10.1161/HYPERTENSIONAHA.109.146795. Epub 2010 Mar 19.

PMID: 20305128 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974436/pdf/nihms242799.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974436/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974436/table/T4/

Abstract

Aging is a multifactorial complex process that leads to the deterioration of biological functions wherein its underlying mechanism is not fully elucidated. It affects the organism at the molecular and cellular level that contributes to the deterioration of structural integrity of the organs. The central nervous system is the most vulnerable organ affected by aging and its effect is highly heterogeneous. Aging causes alteration in the structure, metabolism and physiology of the brain leading to impaired cognitive and motor-neural functions. Dietary restriction (DR), a robust mechanism that extends lifespan in various organisms, ameliorates brain aging by reducing oxidative stress, improving mitochondrial function, activating anti-inflammatory responses, promoting neurogenesis and increasing synaptic plasticity. It also protects and prevents age-related structural changes. DR alleviates many age-associated diseases including neurodegeneration and improves cognitive functions. DR inhibits/activates nutrient signaling cascades such as insulin/IGF-1, mTOR, AMPK and sirtuins. Because of its sensitivity to energy status and hormones, AMPK is considered as the global nutrient sensor. This review will present an elucidative potential role of dietary restriction in the prevention of phenotypic features during aging in brain and its diverse mechanisms.

Comment in

Diet and exercise: blood pressure and cognition: to protect and serve. [Hypertension. 2010]

Does the improvement in insulin sensitivity mediate the beneficial effects of weight loss on cognitive function? [Hypertension. 2010]

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Caloric restriction improves memory in elderly humans.

Witte AV, Fobker M, Gellner R, Knecht S, Flöel A.

Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1255-60. doi: 10.1073/pnas.0808587106. Epub 2009 Jan 26.

PMID: 19171901 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633586/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633586/pdf/zpq1255.pdf

Abstract

Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m(2)) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < -0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.

 

A nonrandomized controlled clinical pilot trial on 8 wk of intermittent fasting (24 h/wk).

Kessler CS, Stange R, Schlenkermann M, Jeitler M, Michalsen A, Selle A, Raucci F, Steckhan N.

Nutrition. 2017 Aug 12. pii: S0899-9007(17)30171-5. doi: 10.1016/j.nut.2017.08.004. [Epub ahead of print]

PMID: 29031771

Abstract

OBJECTIVE:

The aim of the study was to evaluate whether intermittent fasting (IF) is an effective preventive measure, and whether it is feasible for healthy volunteers under every day conditions.

METHODS:

A nonrandomized controlled clinical trial on IF was performed with healthy volunteers over a period of 8 wk, and a subsequent 4-mo follow-up. Outcomes were assessed at baseline, after 8 wk, and after 6 mo. Volunteers who were not interested in fasting served as a control group. Participants in the fasting group were asked to continue their regular nutritional habits on the nonfasting days, whereas the control group maintained their habitual nutrition throughout the whole period. Outcomes included changes of metabolic parameters (insulin, glucose, insulin resistance, insulin-like growth factor-1, brain-derived neurotropic factor, lipids, liver enzymes, hemoglobin A1c) and coagulation markers; bioelectrical impedance analysis; body mass index; abdominal girth; blood pressure; general quality of life (five-item World Health Organization Well-Being Index [WHO-5] questionnaire), as well as mood and anxiety (Hospital Anxiety and Depression Scale [HADS], Profile of Mood States, Flourishing-Scale, visual analog scale, Likert scales). The intervention consisted of a fasting day, which was repeated every week for 8 wk, with abstinence from solid food between 00:00 and 23:59 at minimum and a maximum caloric intake of 300 kcal on each fasting day. A per-protocol analysis was performed. P < 0.05 was considered significant.

RESULTS:

Thirty-six volunteers were included; 22 allocated themselves to the fasting group, and 14 to the control group. Thirty-three data sets were included in the final analysis. Although significant in-group changes were observed in both groups for a number of outcomes after 8 wk and 6 mo, no significant between-group differences were observed for any outcome other than overall body fat mass after 8 wk as well as for the HADS total score and the WHO-5 total score after 6 mo, all in favor of the fasting group. However, none of the between-group differences were clinically relevant.

CONCLUSIONS:

We did not find any clinically relevant differences between groups in this controlled clinical pilot trial of 8 wk of IF in healthy volunteers. Further clinical research in this field is warranted to further analyze mechanisms and effects of IF.

KEYWORDS:

Buchinger fasting; Caloric restriction; Fast; Fasting; Traditional European medicine

 

[The below paper is pdf-availed.]

Can We Increase Our Health Span?

Rivera-Tavarez CE.

Phys Med Rehabil Clin N Am. 2017 Nov;28(4):681-692. doi: 10.1016/j.pmr.2017.08.002. Review.

PMID: 29031335

Abstract

The deterioration of physical and mental capabilities is inevitable with aging. Some hereditary factors cannot be changed, but other external factors can be manipulated to provide our body with better weapons to improve quality of life as we age. Different cellular pathways leading to cell deterioration and aging usually act through excessive oxidative damage and chronic inflammation. Suppression of inflammation is the most important driver of successful longevity and increases in importance with advancing age. Modifying caloric intake, amount and type of food, and maintaining an active lifestyle can decrease the risk of most common chronic diseases of aging.

KEYWORDS:

Aging; Chronic disease; Health span; Inflammation; Lifestyle

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Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle Strength.

Racette SB, Rochon J, Uhrich ML, Villareal DT, DAS SK, Fontana L, Bhapkar M, Martin CK, Redman LM, Fuss PJ, Roberts SB, Kraus WE.

Med Sci Sports Exerc. 2017 Nov;49(11):2240-2249. doi: 10.1249/MSS.0000000000001353.

PMID: 29045325

http://sci-hub.cc/10.1249/MSS.0000000000001353

Abstract

PURPOSE:

Calorie restriction (CR) improves health span and delays age-related diseases in many species. The multicenter Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was the first randomized controlled trial of CR in nonobese humans. The aim of this investigation was to determine the effects of CR on V˙O2max and muscle strength in the CALERIE trial.

METHODS:

Healthy, normal-weight, and mildly overweight women and men (n = 218, mean ± SE age = 37.9 ± 0.5 yr) were randomized to 25% CR or an ad libitum (AL) control condition in a 2:1 allocation (143 CR, 75 AL). V˙O2max was determined with an incremental treadmill test; the strength of the knee flexors and extensors was assessed by dynamometry at baseline, 1 yr, and 2 yr.

RESULTS:

The CR group achieved an average 11.9% ± 0.7% CR during the 2-yr intervention. Body weight decreased in CR (-7.7 ± 0.4 kg), but not AL (+0.2 ± 0.5 kg). Absolute V˙O2max (L·min) decreased at 1 and 2 yr with CR, whereas V˙O2max expressed relative to body mass increased at both time points (1 yr: +2.2 ± 0.4; 2 yr: +1.9 ± 0.5 mL·kg·min) and relative to AL. The CR group increased their treadmill test time and workload at 1 and 2 yr. Strength results in CR were similar, with decreases in absolute flexor and extensor strength, but increases when expressed relative to body mass. No changes were observed for V˙O2max expressed relative to lean body mass or leg lean mass.

CONCLUSIONS:

Two years of modest CR without a structured exercise component did not appear to compromise aerobic capacity in healthy nonobese adults. The clinical implications of the observed changes in V˙O2max and muscle strength will be important to explore in future studies.

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Living Too Long? Exploring Attitudes Toward Reaching 100 Years Old.

Ribeiro O, Canedo S, Cerqueira M, Nascimento A, Teixeira L.

Int J Aging Hum Dev. 2017 Jan 1:91415017720886. doi: 10.1177/0091415017720886. [Epub ahead of print]

PMID: 29048212

Abstract

Objective This study analyses the relationship between pro- and anti-longevity attitudes, attitudes toward centenarians, and the wish to reach 100 years of age in a sample of community dwelling older adults. Methods Participants ( N = 137) completed a questionnaire on attitudes toward life-extension and an aging semantic differential using centenarians as an attitudinal target. Sociodemographic information, perceived health status, and information on knowing a centenarian were also obtained. A cluster analysis was used to identify subgroups (leaning anti-longevity group vs. leaning prolongevity group), and their associations with personal attributes were tested using logistic regression models. Results Most respondents said they would wish to reach 100 years old (54.7%) and presented a leaning positive attitude toward centenarians (52.6%). Holding a negative attitude toward centenarians rather than any other attribute increases the odds of having more negative attitudes toward life extension. Conclusion Results stress the importance of social views on extreme longevity in shaping life extension attitudes.

KEYWORDS:

ageism; attitudes; centenarians; life extension; longevity

 

Nutrition, physical activity, and lifestyle factors in prostate cancer prevention.

Ballon-Landa E, Parsons JK.

Curr Opin Urol. 2017 Oct 18. doi: 10.1097/MOU.0000000000000460. [Epub ahead of print]

PMID: 29049045

Abstract

PURPOSE OF REVIEW:

To review current evidence for prostate cancer prevention with nutrition, physical activity, and lifestyle interventions and identify future research directions.

RECENT FINDINGS:

Multiple preclinical and observational studies have observed that diet, exercise, and lifestyle interventions may play a role in mitigating disease progression, mortality, and overall disease burden for high-grade and fatal prostate cancer. Increased vegetable and fruit intakes, decreased red meat and saturated fat intakes, and increased exercise are potentially associated with decreased risk of incident disease and increased progression-free, prostate cancer-specific, and overall survival. Randomized controlled trials (RCTs) have demonstrated that selenium and vitamin C supplements are ineffective in preventing incident prostate cancer and that vitamin E supplements potentially increase incident prostate cancer risk. A large RCT of a high vegetable diet intervention among prostate cancer patients on active surveillance, the Men's Eating and Living study, will soon complete analysis. An RCT for an exercise intervention among men with metastatic castrate-resistant prostate cancer is currently accruing.

SUMMARY:

Although preclinical and observational studies have identified potential benefits for high vegetable, low fat, low meat diets, and increased exercise, Level I evidence is limited. To inform clinical care, future research should focus on RCTs evaluating clinical effectiveness.

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Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH.

JAMA. 2011 Oct 12;306(14):1549-56. doi: 10.1001/jama.2011.1437.

PMID: 21990298 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169010/pdf/nihms551257.pdf

 

[The below paper is not pdf-availed.]

Should Pre-hypertension Be Treated?

Kanegae H, Oikawa T, Kario K.

Curr Hypertens Rep. 2017 Oct 18;19(11):91. doi: 10.1007/s11906-017-0789-z. Review.

PMID: 29046988

Abstract

Hypertension is an important preventable risk factor for disease and death worldwide. In light of the world's population growth and aging, hypertension is a global public health issue. Many studies have shown associations between pre-hypertension and a higher risk of the future development of hypertension and cardiovascular disease in general populations. However, pre-hypertension per se is not a disease with an immediate high risk, and the clinical value of the identification of pre-hypertension is the potential detection of the early stage of the risk of hypertension and/or cardiovascular disease over an individual's lifespan. We recently assessed the impacts of age-related differences in risk factors on new-onset hypertension among normotensive individuals. As risk factors of the new onset of hypertension, the impact of diastolic blood pressure compared with systolic blood pressure (SBP), men compared with women, and higher body mass index were greater in the younger adults, whereas in the older adults, the impact of SBP and female sex were greater. Proteinuria was a risk factor for hypertension in both younger and older adults. Non-pharmacological approaches such as body weight reduction, low-salt diet, physical exercise, and good sleep hygiene should be first-line treatments for pre-hypertension. In addition, careful observation to detect the new onset of hypertension and the identification of the appropriate timing of pharmacologic treatment should be conducted, especially in adults with pre-hypertension and the risk factors mentioned above.

KEYWORDS:

Aging; Hypertension; Obesity; Pre-hypertension; Prevention of hypertension; Risk

 

xxx

 

 

High adherence to the Mediterranean diet is associated with cardiovascular protection in higher but not in lower socioeconomic groups: prospective findings from the Moli-sani study.

Bonaccio M, Di Castelnuovo A, Pounis G, Costanzo S, Persichillo M, Cerletti C, Donati MB, de Gaetano G, Iacoviello L; Moli-sani Study Investigators.

Int J Epidemiol. 2017 Aug 1. doi: 10.1093/ije/dyx145. [Epub ahead of print]

PMID: 29040542

https://sci-hub.cc/http://fdslive.oup.com/www.oup.com/pdf/production_in_progress.pdf

Abstract

BACKGROUND:

It is uncertain whether the cardiovascular benefits associated with Mediterranean diet (MD) may differ across socioeconomic groups.

METHODS:

Prospective analysis on 18991 men and women aged ≥35 years from the general population of the Moli-sani cohort (Italy). Adherence to MD was appraised by the Mediterranean diet score (MDS). Household income (euros/year) and educational level were used as indicators of socioeconomic status. Hazard ratios (HR) were calculated by multivariable Cox proportional hazard models.

RESULTS:

Over 4.3 years of follow-up, 252 cardiovascular disease (CVD) events occurred. Overall, a two-point increase in MDS was associated with 15% reduced CVD risk (95% confidence interval: 1% to 27%). Such association was evident in highly (HR = 0.43; 0.25-0.72) but not in less (HR = 0.94; 0.78-1.14) educated subjects ( P for interaction = 0.042). Similarly, CVD advantages associated with the MD were confined to the high household income group (HR = 0.39; 0.23-0.66, and HR = 1.01; 0.79-1.29 for high- and low-income groups, respectively; P for interaction = 0.0098). In a subgroup of individuals of different socioeconomic status but sharing similar MDS, diet-related disparities were found as different intakes of antioxidants and polyphenols, fatty acids, micronutrients, dietary antioxidant capacity, dietary diversity, organic vegetables and whole grain bread consumption.

CONCLUSIONS:

MD is associated with lower CVD risk but this relationship is confined to higher socioeconomic groups. In groups sharing similar scores of adherence to MD, diet-related disparities across socioeconomic groups persisted. These nutritional gaps may reasonably explain at least in part the socioeconomic pattern of CVD protection from the MD.

KEYWORDS:

Cardiovascular disease; Mediterranean diet; coronary heart disease; interaction; socioeconomic status; stroke

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Caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of a quiescent state, entry into a non-quiescent state and survival in the non-quiescent state.

Leonov A, Feldman R, Piano A, Arlia-Ciommo A, Lutchman V, Ahmadi M, Elsaser S, Fakim H, Heshmati-Moghaddam M, Hussain A, Orfali S, Rajen H, Roofigari-Esfahani N, Rosanelli L, Titorenko VI.

Oncotarget. 2017 Sep 1;8(41):69328-69350. doi: 10.18632/oncotarget.20614. eCollection 2017 Sep 19.

PMID: 29050207

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=20614&path%5B%5D=65691

Abstract

A yeast culture grown in a nutrient-rich medium initially containing 2% glucose is not limited in calorie supply. When yeast cells cultured in this medium consume glucose, they undergo cell cycle arrest at a checkpoint in late G1 and differentiate into quiescent and non-quiescent cell populations. Studies of such differentiation have provided insights into mechanisms of yeast chronological aging under conditions of excessive calorie intake. Caloric restriction is an aging-delaying dietary intervention. Here, we assessed how caloric restriction influences the differentiation of chronologically aging yeast cultures into quiescent and non-quiescent cells, and how it affects their properties. We found that caloric restriction extends yeast chronological lifespan via a mechanism linking cellular aging to cell cycle regulation, maintenance of quiescence, entry into a non-quiescent state and survival in this state. Our findings suggest that caloric restriction delays yeast chronological aging by causing specific changes in the following: 1) a checkpoint in G1 for cell cycle arrest and entry into a quiescent state; 2) a growth phase in which high-density quiescent cells are committed to become low-density quiescent cells; 3) the differentiation of low-density quiescent cells into low-density non-quiescent cells; and 4) the conversion of high-density quiescent cells into high-density non-quiescent cells.

KEYWORDS:

Gerotarget; cell cycle; cell differentiation; cell quiescence; cellular aging; yeast

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[The below paper is pdf-availed.]

Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: Role of perivascular adipose tissue.

Amor S, Martín-Carro B, Rubio C, Carrascosa JM, Hu W, Huang Y, García-Villalón AL, Granado M.

Exp Gerontol. 2017 Oct 18. pii: S0531-5565(17)30591-0. doi: 10.1016/j.exger.2017.10.017. [Epub ahead of print]

PMID: 29055722

Abstract

The prevalence of metabolic syndrome is dramatically increasing among elderly population. Metabolic syndrome in aged individuals is associated with hyperinsulinemia and insulin resistance both in metabolic tissues and in the cardiovascular system, with this fact being associated with the cardiometabolic alterations associated to this condition. Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of CR in aging-induced vascular insulin resistance both in aortic rings and in primary culture of endothelial cells. In addition, the inflammatory profile of perivascular adipose tissue (PVAT) and its possible role in the impairment of vascular insulin sensitivity associated with aging was also assessed. Three experimental groups of male Wistar rats were used: 3 (3m), 24 (24m) fed ad libitum and 24months old rats subjected to 20% CR during their three last months of life (24m-CR). Aorta rings surrounded or not by PVAT were mounted in an organ bath and precontracted with phenylephrine (10-7.5M). Changes in isometric tension were recorded in response to cumulative insulin concentrations (10-8-10-5.5M) in the presence or absence of L-NAME (10-4M). Aortic rings and primary aortic endothelial cells were incubated in presence/absence of insulin (10-7M) and the activation of the PI3K/Akt and MAPK pathways as well as nitrite and nitrates concentrations and the mRNA levels of eNOS, insulin receptor, and GLUT-4 were assessed. CR prevented the aging-induced decrease in the vasodilator response to insulin and the aging-induced increase in the vasoconstrictor response to high insulin concentrations. Changes between 24m and 24m-CR aorta rings were abolished in the presence of L-NAME. CR induced-improvement in insulin vascular sensitivity was related with activation of the PI3K/Akt both in aortic rings and in aortic endothelial cells in response to insulin. CR attenuated the overexpression of iNOS, TNF-α and IL-1β in the PVAT of aged rats although aortic rings surrounded by PVAT from 24m rats showed and increased vasorelaxation in response to insulin compared to aortic rings from 3m and 24m-CR rats. In conclusion, a moderate protocol of CR improves insulin vascular sensitivity and prevents the aging induced overexpression of pro-inflammatory cytokines in PVAT.

KEYWORDS:

Aging; Akt; Aorta; Insulin; Perivascular adipose tissue; eNOS

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Effects of Dairy Products Consumption on Body Weight and Body Composition Among Adults: An Updated Meta-Analysis of 37 Randomized Control Trials.

Geng T, Qi L, Huang T.

Mol Nutr Food Res. 2017 Oct 23. doi: 10.1002/mnfr.201700410. [Epub ahead of print]

PMID: 29058378

http://sci-hub.cc/http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201700410/abstract;jsessionid=45ACB83519EDC8B22D18BA1D9303410A.f04t03

Abstract

SCOPE:

Effects of dairy consumption on body weight and body composition have been inconsistently observed in randomized control trials (RCTs). Our meta-analysis aimed to systematically evaluate the effects of dairy consumption on body weight and body composition among the adults.

METHODS AND RESULTS:

We conducted a comprehensive search of the Cochrane Library, PubMed and Embase databases of the relevant studies from 1966 to Mar 2017 regarding dairy consumption on body weight and body composition including of body fat, lean mass and waist circumference (WC). The summary results were pooled by using a random-effects meta-analysis. 37 RCTs with 184,802 participants were included in this meta-analysis. High dairy intervention increased body weight (0.01, 95% CI: -0.25, 0.26, I2 = 78.3%) and lean mass (0.37, 95% CI: 0.11, 0.62, I2 = 83.4%); decreased body fat (-0.23, 95% CI: -0.48, 0.02, I2 = 78.2%) and WC (-1.37, 95% CI: -2.28, -0.46, I2 = 98.9%) overall. In the subgroup analysis, consumption of dairy products increased body weight (0.36, 95% CI: 0.01, 0.70, I2 = 83.1%) among participants without energy restriction. Dairy consumption decreased body weight (-0.64, 95% CI: -1.05, -0.24, I2 = 60.2%), body fat (-0.56, 95%CI: -0.95, -0.17, I2 = 66.6%) and waist circumference (-2.18, 95%CI: -4.30, -0.06, I2 = 99.0%) among the adults with energy restriction.

CONCLUSIONS:

This meta-analysis suggests a beneficial effect of energy-restricted dairy consumption on body weight and body composition. However, high dairy consumption in the absence of caloric restriction may increase body weight. This article is protected by copyright. All rights reserved.

KEYWORDS:

body composition; body weight; dairy products; meta-analysis; waist circumference

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Health Benefits of Fasting and Caloric Restriction.

Golbidi S, Daiber A, Korac B, Li H, Essop MF, Laher I.

Curr Diab Rep. 2017 Oct 23;17(12):123. doi: 10.1007/s11892-017-0951-7. Review.

PMID: 29063418

http://sci-hub.cc/10.1007/s11892-017-0951-7

Abstract

PURPOSE OF REVIEW:

Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes.

RECENT FINDINGS:

Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

KEYWORDS:

Adipose tissue; Calorie restriction; Diabetes; Oxidative stress

 

Intermittent fasting shows promise as therapy for diabetes, metabolic diseases

Oct 23, 2017 | Anicka Slachta

http://www.cardiovascularbusiness.com/topics/lipid-metabolic/intermittent-fasting-shows-promise-therapy-diabetes-metabolic-diseases

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Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

Kim KH, Kim YH, Son JE, Lee JH, Kim S, Choe MS, Moon JH, Zhong J, Fu K, Lenglin F, Yoo JA, Bilan PJ, Klip A, Nagy A, Kim JR, Park JG, Hussein SM, Doh KO, Hui CC, Sung HK.

Cell Res. 2017 Oct 17. doi: 10.1038/cr.2017.126. [Epub ahead of print]

PMID: 29039412

http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2017126a.html

https://www.nature.com/cr/journal/vaop/ncurrent/pdf/cr2017126a.pdf

Abstract

Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

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Circadian rhythms, nutrition and implications for longevity in urban environments.

Froy O.

Proc Nutr Soc. 2017 Oct 25:1-7. doi: 10.1017/S0029665117003962. [Epub ahead of print]

PMID: 29065948

Abstract

Presently, about 12% of the population is 65 years or older and by the year 2030 that figure is expected to reach 21%. In order to promote the well-being of the elderly and to reduce the costs associated with health care demands, increased longevity should be accompanied by ageing attenuation. Energy restriction, which limits the amount of energy consumed to 60-70% of the daily intake, and intermittent fasting, which allows the food to be available ad libitum every other day, extend the life span of mammals and prevent or delay the onset of major age-related diseases, such as cancer, diabetes and cataracts. Recently, we have shown that well-being can be achieved by resetting of the circadian clock and induction of robust catabolic circadian rhythms via timed feeding. In addition, the clock mechanism regulates metabolism and major metabolic proteins are key factors in the core clock mechanism. Therefore, it is necessary to increase our understanding of circadian regulation over metabolism and longevity and to design new therapies based on this regulation. This review will explore the present data in the field of circadian rhythms, ageing and metabolism.

KEYWORDS:

BMAL1 brain-muscle-Arnt-like 1; CR calorie restriction; CRY cryptochromes; IF intermittent fasting; PER Periods; RF restricted feeding; SCN suprachiasmatic nuclei; Circadian rhythms; Clock; Feeding; Life span; Metabolism; Nutrition

 

Testosterone and corticosterone in the mesocorticolimbic system of male rats: effects of gonadectomy and caloric restriction.

Tobiansky DJ, Korol AM, Ma C, Hamden JE, Jalabert C, Tomm RJ, Soma KK.

Endocrinology. 2017 Oct 20. doi: 10.1210/en.2017-00704. [Epub ahead of print]

PMID: 29069423

Abstract

Steroid hormones can modulate motivated behaviors through the mesocorticolimbic system. Gonadectomy (GDX) is a common method to determine how steroids influence the mesocorticolimbic system and caloric restriction (CR) is often used to invigorate motivated behaviors. The assumption is that the effect of these manipulations on brain steroid levels reflects circulating steroid levels. We now know that the brain regulates local steroid levels in a region-specific manner; however, previous studies have low spatial resolution. Using ultrasensitive liquid chromatography tandem mass spectrometry (LC-MS/MS), we examined steroids in microdissected regions of the mesocorticolimbic system (ventral tegmental area, nucleus accumbens, medial prefrontal cortex). We examined whether GDX or CR influence systemic and local steroids, particularly testosterone (T) and steroidogenic enzyme transcripts. Adult male rats underwent a GDX surgery and/or CR for either 2 or 6 wk. Levels of T, the primary steroid of interest, were higher in all brain regions than in the blood, while corticosterone (CORT) was lower in the brain than in the blood. Importantly, GDX completely eliminated T in the blood and lowered it in the brain. Yet, T remained present in the brain even 6 wk after GDX. CR decreased both T and CORT in the blood and brain. Steroidogenic enzymes (Cyp17a1, 3β-HSD, aromatase) and androgen receptor were expressed in the mesocorticolimbic system and differentially affected by GDX and CR. Together, these results suggest that T is synthesized within the mesocorticolimbic system. These results provide a foundation for future studies examining how neurosteroids influence behaviors mediated by the mesocorticolimbic system.

 

A novel caloric restriction mediator.

Kobayashi M, Higami Y.

Aging (Albany NY). 2017 Oct 25. doi: 10.18632/aging.101311. [Epub ahead of print] No abstract available.

PMID: 29070730

KEYWORDS:

caloric restriction (CR); sterol regulatory element binding protein-1c (Srebp-1c)

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Sterol regulatory element-binding protein-1c orchestrates metabolic remodeling of white adipose tissue by caloric restriction.

Fujii N, Narita T, Okita N, Kobayashi M, Furuta Y, Chujo Y, Sakai M, Yamada A, Takeda K, Konishi T, Sudo Y, Shimokawa I, Higami Y.

Aging Cell. 2017 Jun;16(3):508-517. doi: 10.1111/acel.12576. Epub 2017 Mar 3.

PMID: 28256090 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418191/

Abstract

Caloric restriction (CR) can delay onset of several age-related pathophysiologies and extend lifespan in various species, including rodents. CR also induces metabolic remodeling involved in activation of lipid metabolism, enhancement of mitochondrial biogenesis, and reduction of oxidative stress in white adipose tissue (WAT). In studies using genetically modified mice with extended lifespans, WAT characteristics influenced mammalian lifespans. However, molecular mechanisms underlying CR-associated metabolic remodeling of WAT remain unclear. Sterol regulatory element-binding protein-1c (Srebp-1c), a master transcription factor of fatty acid (FA) biosynthesis, is responsible for the pathogenesis of fatty liver (steatosis). Our study showed that, under CR conditions, Srebp-1c enhanced mitochondrial biogenesis via increased expression of peroxisome proliferator-activated receptor gamma coactivator-1α (Pgc-1α) and upregulated expression of proteins involved in FA biosynthesis within WAT. However, via Srebp-1c, most of these CR-associated metabolic alterations were not observed in other tissues, including the liver. Moreover, our data indicated that Srebp-1c may be an important factor both for CR-associated suppression of oxidative stress, through increased synthesis of glutathione in WAT, and for the prolongevity action of CR. Our results strongly suggested that Srebp-1c, the primary FA biosynthesis-promoting transcriptional factor implicated in fatty liver disease, is also the food shortage-responsive factor in WAT. This indicated that Srebp-1c is a key regulator of metabolic remodeling leading to the beneficial effects of CR.

KEYWORDS:

caloric restriction (CR); mitochondria biogenesis; oxidative stress; peroxisome proliferator-activated receptor gamma coactivator-1α (Pgc-1α); sterol regulatory element binding protein-1c (Srebp-1c); white adipose tissue (WAT)

 

Understanding mitochondrial biogenesis through energy sensing pathways and its translation in cardio-metabolic health.

Nirwane A, Majumdar A.

Arch Physiol Biochem. 2017 Oct 26:1-13. doi: 10.1080/13813455.2017.1391847. [Epub ahead of print]

PMID: 29072101

https://sci-hub.cc/https://www.tandfonline.com/doi/full/10.1080/13813455.2017.1391847

Abstract

Mitochondria play a pivotal role in physiological energy governance. Mitochondrial biogenesis comprises growth and division of pre-existing mitochondria, triggered by environmental stressors such as endurance exercise, caloric restriction, cold exposure and oxidative stress. For normal physiology, balance between energy intake, storage and expenditure is of utmost important for the coordinated regulation of energy homeostasis. In contrast, abnormalities in these regulations render the individual susceptible to cardiometabolic disorders. This review provides a comprehensive coverage and understanding on mitochondrial biogenesis achieved through energy-sensing pathways. This includes the complex coordination of nuclear, cytosolic and mitochondrial events involving energy sensors, transcription factors, coactivators and regulators. It focuses on the importance of mitochondrial biogenesis in cardiometabolic health. Lastly, converging on the benefits of caloric restriction and endurance exercise in achieving cardiometabolic health.

KEYWORDS:

Mitochondrial biogenesis; PGC-1α; SIRT1; cardiovascular diseases; diabetes

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[The below paper is pdf-availed.]

Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth.

Ma D, Chen X, Zhang PY, Zhang H, Wei LJ, Hu S, Tang JZ, Zhou MT, Xie C, Ou R, Xu Y, Tang KF.

Oncogene. 2017 Oct 30. doi: 10.1038/onc.2017.398. [Epub ahead of print]

PMID: 29084207

Abstract

Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.

 

[The below paper is pdf-availed. Arg in CRed subjects significantly increased IGF-1 about 80% and decreased glucose quite a bit (P=0.08) without significantly changing body weight. "In the caloric restriction experiment, twenty twelve-week-old male littermates were received 60% of the average value of food intake for 18 days. Arg was supplemented by drinking water (1.5%, pH 7.0)."]

Arginine Reverses Growth Hormone Resistance through the Inhibition of Toll-like Receptor 4-Mediated Inflammatory Pathway.

Xu J, Zhu C, Zhang M, Tong Q, Wan X, Liao Z, Cai X, Xu Y, Yuan Y, Wang L, Zhu X, Wang S, Gao P, Xi Q, Xu Y, Jiang Q, Shu G.

Metabolism. 2017 Oct 25. pii: S0026-0495(17)30280-9. doi: 10.1016/j.metabol.2017.10.006. [Epub ahead of print]

PMID: 29080813

Abstract

OBJECTIVE:

Growth hormone stimulates growth by increasing insulin-like growth factor 1 expression and secretion. In the presence of insufficient nutrients, GH increases, whereas IGF-1 expression becomes severely suppressed, leading to GH resistance. This study aimed to explore the effect of arginine (Arg) on GH resistance during malnutrition and to describe its underlying mechanism.

METHODS:

C57BL/6J mice were injected intraperitoneally with Arg for 1 h or subjected to caloric restriction with Arg supplement in drinking water for 18 days. HepG2 cells were exposed to different Arg concentrations for 24 h. Signaling pathway agonists/inhibitors, siRNA, and overexpression plasmids were used to investigate the underlying molecular mechanism. Liver-specific toll-like receptor (TLR4) knockout mice were utilized to clarify the role of TLR4 in Arg-induced IGF-I expression and secretion.

RESULTS:

Arg inhibited the TLR4 downstream pathway by binding to TLR4 and consequently activated Janus kinase 2/signal transducer and activator of transcription 5 signaling pathway. As a result, IGF-1 transcription and secretion increased. Arg activity was absent in liver-specific TLR4 knockout mice and was greatly suppressed in liver with overexpressed TLR4, suggesting that hepatic TLR4 was required and sufficient to induce GH resistance. By contrast, the mammalian target of rapamycin pathway was unnecessary for Arg activity. Arg not only significantly increased IGF-1 expression and secretion under acute fasting and chronic CR conditions but also attenuated body weight loss.

CONCLUSIONS:

Our results demonstrate a previously unappreciated pathway involving Arg that reverses GH resistance and alleviates malnutrition-induced growth restriction through the inhibition of TLR4-mediated inflammatory pathway.

KEYWORDS:

Arginine; HepG2 cells; IGF-1; Liver; Malnutrition; TLR4

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Assessing the evidence for weight loss strategies in people with and without type 2 diabetes.

Clifton P.

World J Diabetes. 2017 Oct 15;8(10):440-454. doi: 10.4239/wjd.v8.i10.440. Review.

PMID: 29085571

Abstract

This review will examine topical issues in weight loss and weight maintenance in people with and without diabetes. A high protein, low glycemic index diet would appear to be best for 12-mo weight maintenance in people without type 2 diabetes. This dietary pattern is currently being explored in a large prevention of diabetes intervention. Intermittent energy restriction is useful but no better than daily energy restriction but there needs to be larger and longer term trials performed. There appears to be no evidence that intermittent fasting or intermittent severe energy restriction has a metabolic benefit beyond the weight loss produced and does not spare lean mass compared with daily energy restriction. Meal replacements are useful and can produce weight loss similar to or better than food restriction alone. Very low calorie diets can produce weight loss of 11-16 kg at 12 mo with persistent weight loss of 1-2 kg at 4-6 years with a very wide variation in long term results. Long term medication or meal replacement support can produce more sustained weight loss. In type 2 diabetes very low carbohydrate diets are strongly recommended by some groups but the long term evidence is very limited and no published trial is longer than 12 mo. Although obesity is strongly genetically based the microbiome may play a small role but human evidence is currently very limited.

KEYWORDS:

Alternate day fasting; Glycemic index; Intermittent energy restriction; Low fat diets; Protein; Very low calorie diet; Very low carbohydrate diet

 

Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting.

Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP.

Obesity (Silver Spring). 2017 Oct 31. doi: 10.1002/oby.22065. [Epub ahead of print] Review.

PMID: 29086496

http://onlinelibrary.wiley.com/doi/10.1002/oby.22065/full

http://onlinelibrary.wiley.com/doi/10.1002/oby.22065/epdf

Abstract

OBJECTIVE:

Objective: Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. This review is focused on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch: the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake).

RESULTS AND CONCLUSIONS:

Emerging findings suggest that the metabolic switch from glucose to fatty acid-derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty acid-derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and of the magnitude of negative energy balance during the fasting period.

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Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.

Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, Laboy R, Hirschey MD, Mair WB.

Cell Metab. 2017 Oct 23. pii: S1550-4131(17)30612-5. doi: 10.1016/j.cmet.2017.09.024. [Epub ahead of print]

PMID: 29107506

http://sci-hub.cc/10.1016/j.cmet.2017.09.024

Abstract

Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles, and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity in C. elegans via maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly, however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity. Finally, we show that increasing lifespan via maintaining mitochondrial network homeostasis requires FAO and peroxisomal function. Together, these data demonstrate that mechanisms that promote mitochondrial homeostasis and plasticity can be targeted to promote healthy aging.

KEYWORDS:

AMPK; aging; dietary restriction; fatty acid oxidation; intermittent fasting; longevity; mitochondrial dynamics; peroxisomes

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Analysis of energy restriction and physical activity on brain function: the role of ketone body and brain-derived neurotrophic factor.

Park CH, Kwak YS.

J Exerc Rehabil. 2017 Aug 29;13(4):378-380. doi: 10.12965/jer.1735028.514. eCollection 2017 Aug. Review.

PMID: 29114500

https://www.e-jer.org/journal/view.php?number=2013600397

Abstract

Brain development is a complex process, and stimuli during this development period may modulate the functional maturation of the brain. It has been shown that environmental stimuli, such as physical activity habits, have a beneficial effect on brain development. Endurance exercise and prolonged fasting state are known to improve brain function including cognition. The exact mechanisms of exercise improving brain function are still unknown. However, it can be considered that energy restriction and stressful challenge induced by long-lasting physical exercise might cause direct effect on brain function. Upregulation of brain-derived neurotrophic factor and ketone body caused by exercise might be considered as the mechanism of exercise on brain function. In the present study, we discussed on two main topics: "exercise and BDNF" and "exercise and energy restriction."

KEYWORDS:

Brain-derived neurotrophic factor; Energy restriction; Ketone body; Physical activity

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Ketone body 3-hydroxybutyrate mimics calorie restriction via the Nrf2 activator, fumarate, in the retina.

Izuta Y, Imada T, Hisamura R, Oonishi E, Nakamura S, Inagaki E, Ito M, Soga T, Tsubota K.

Aging Cell. 2017 Nov 9. doi: 10.1111/acel.12699. [Epub ahead of print]

PMID: 29119686

http://onlinelibrary.wiley.com/doi/10.1111/acel.12699/full

http://onlinelibrary.wiley.com/doi/10.1111/acel.12699/epdf

Abstract

Calorie restriction (CR) being the most robust dietary intervention provides various health benefits. D-3-hydroxybutyrate (3HB), a major physiological ketone, has been proposed as an important endogenous molecule for CR. To investigate the role of 3HB in CR, we investigated potential shared mechanisms underlying increased retinal 3HB induced by CR and exogenously applied 3HB without CR to protect against ischemic retinal degeneration. The repeated elevation of retinal 3HB, with or without CR, suppressed retinal degeneration. Metabolomic analysis showed that the antioxidant pentose phosphate pathway and its limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD), were concomitantly preserved. Importantly, the upregulation of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a regulator of G6PD, and elevation of the tricarboxylic acid cycle's Nrf2 activator, fumarate, were also shared. Together, our findings suggest that CR provides retinal antioxidative defense by 3HB through the antioxidant Nrf2 pathway via modification of a tricarboxylic acid cycle intermediate during 3HB metabolism.

KEYWORDS:

3-hydroxy butyrate; calorie restriction; ketone body; retinal protection

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Effect of short term diet restriction on gene expression in the bovine hypothalamus using next generation RNA sequencing technology.

Matthews D, Diskin MG, Kenny DA, Creevey CJ, Keogh K, Waters SM.

BMC Genomics. 2017 Nov 9;18(1):857. doi: 10.1186/s12864-017-4265-6.

PMID: 29121875

https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-4265-6

Abstract

BACKGROUND:

Negative energy balance (NEB) is an imbalance between energy intake and energy requirements for lactation and body maintenance affecting high-yielding dairy cows and is of considerable economic importance due to its negative impact on fertility and health in dairy herds. It is anticipated that the cow hypothalamus experiences extensive biochemical changes during the early post partum period in an effort to re-establish metabolic homeostasis. However, there is variation in the tolerance to NEB between individual cows. In order to understand the genomic regulation of ovulation in hypothalamic tissue during NEB, mRNA transcriptional patterns between tolerant and sensitive animals were examined. A short term dietary restriction heifer model was developed which induced abrupt onset of anoestrus in some animals (Restricted Anovulatory; RA) while others maintained oestrous cyclicity (Restricted Ovulatory; RO). A third control group © received a higher level of normal feeding.

RESULTS:

A total of 15,295 genes were expressed in hypothalamic tissue. Between RA and C groups 137 genes were differentially expressed, whereas between RO and C, 32 genes were differentially expressed. Differentially expressed genes were involved in the immune response and cellular motility in RA and RO groups, respectively, compared to C group. The largest difference between groups was observed in the comparison between RA and RO heifers, with 1094 genes shown to be significantly differentially expressed (SDE). Pathway analysis showed that these SDE genes were associated with 6 canonical pathways (P < 0.01), of which neuroactive ligand-receptor interaction was the most significant. Within the comparisons the main over-represented pathway functions were immune response including neuroprotection (CXCL10, Q1KLR3, IFIH1, IL1 and IL8; RA v C and RA v RO); energy homeostasis (AgRP and NPY; RA v RO); cell motility (CADH1, DSP and TSP4; RO v C) and prevention of GnRH release (NTSR1 IL1α, IL1β, NPY and PACA; RA v RO).

CONCLUSIONS:

This information will assist in understanding the genomic factors regulating the influence of diet restriction on fertility and may assist in optimising nutritional and management systems for the improvement in reproductive performance.

KEYWORDS:

Bovine; Dietary restriction; Energy homeostasis; Hypothalamus; Reproduction; mRNAseq

 

Evolutionarily adapted hormesis-inducing stressors can be a practical solution to mitigate harmful effects of chronic exposure to low dose chemical mixtures.

Kim SA, Lee YM, Choi JY, Jacobs DR Jr, Lee DH.

Environ Pollut. 2017 Nov 7;233:725-734. doi: 10.1016/j.envpol.2017.10.124. [Epub ahead of print] Review.

PMID: 29126094

http://sci-hub.cc/10.1016/j.envpol.2017.10.124

Abstract

Although the toxicity of synthetic chemicals at high doses is well known, chronic exposure to low-dose chemical mixtures has only recently been linked to many age-related diseases. However, it is nearly impossible to avoid the exposure to these low-dose chemical mixtures as humans are exposed to a myriad of synthetic chemicals as a part of their daily lives. Therefore, coping with possible harms due to low dose chemical mixtures is challenging. Interestingly, within the range of environmental exposure, disease risk does not increase linearly with increasing dose of chemicals, but often tends to plateau or even decrease with increasing dose. Hormesis, the over-compensation of various adaptive responses through cellular stresses, is one possible mechanism for this non-linearity. Although the hormetic effects of synthetic chemicals or radiation have long been debated in the field of toxicology, the hormesis concept has recently been generalized in the field of molecular biology; similar to responses to synthetic chemicals, mild to moderate intermittent stressors from any source can induce hormetic responses. Examples of stressors are exercise, calorie restriction, intermittent fasting, cognitive stimulation, and phytochemicals. Mitohormesis is hormesis induced by such stressors through mitochondrial retrograde signalling including the increased production of mild reactive oxygen species. Xenohormesis is phytochemical-induced hormesis, reflective of a mutualistic relationship between plant and animals. As humans had repeated exposure to all of these stressors during their evolution, the hormetic effects of these health behaviours may be considered to be evolutionarily adapted. Although hormesis induced by synthetic chemicals occurs in humans, such hormesis may not be recommended to the public due to unresolved issues on safety including the impossibility of control exposure. However, the use of personal health behaviors which enhance mitohormetic- or xenohormetic-stress can be readily incorporated into everyone's daily lives as a practical way to counteract harmful effects of unavoidable low-dose chemical mixtures.

KEYWORDS:

Chemical mixtures; Hormesis; Mitohormesis; Non-monotonic dose response relation; Persistent organic pollutants; Xenohormesis

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Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes.

Perry RJ, Peng L, Cline GW, Wang Y, Rabin-Court A, Song JD, Zhang D, Zhang XM, Nozaki Y, Dufour S, Petersen KF, Shulman GI.

Cell Metab. 2017 Nov 8. pii: S1550-4131(17)30616-2. doi: 10.1016/j.cmet.2017.10.004. [Epub ahead of print]

PMID: 29129786

http://sci-hub.cc/10.1016/j.cmet.2017.10.004

Abstract

Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. In addition, VLCD resulted in reductions in hepatic triglyceride and diacylglycerol content and PKCɛ translocation, associated with improved hepatic insulin sensitivity. Taken together, these data show that there are pleotropic mechanisms by which VLCD reverses hyperglycemia in a rat model of T2D, including reduced DAG-PKCɛ-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.

KEYWORDS:

T2D; acetyl-CoA; caloric restriction; gluconeogenesis; glycogenolysis; type 2 diabetes; very low calorie diet; very-low-calorie diet

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Life-long moderate caloric restriction prolongs reproductive life span in rats without interrupting estrous cyclicity: effects on the gonadotropin-releasing hormone/luteinizing hormone axis.

McShane TM, Wise PM.

Biol Reprod. 1996 Jan;54(1):70-5.

PMID: 8838002

Abstract

Restricting food intake to 60% that of ad libitum-fed rats results in an extended life span, reduced incidence of age-related diseases, and delayed reproductive senescence. We used this animal model to further elucidate the mechanisms whereby reproductive senescence is delayed. Female Sprague-Dawley rats (7 wk old) were calorically restricted (CR; n = 70) to 60% of the ad libitum(AL) intake measured in control rats (n = 70). Rats were individually housed under a 14L:10D cycle and fed daily within 1.5 h of lights-off. Body weights were monitored every 2 wk, and vaginal lavage was performed until rats were ovariectomized (OVX). Two weeks after OVX, when rats were 4, 12, or 18 mo of age, blood samples were taken via jugular cannulae every 6 min for 3 h, and the plasma was assayed for rat LH. The resulting profiles were examined through use of Cluster analysis for mean LH concentrations, LH pulse amplitude, and interval between LH pulses. CR rats grew at a slower rate, and then maintained body weights at approximately 76% that of AL controls between 4 and 17.5 mo of age. The onset of persistent estrus was delayed by 4 mo in CR rats. Average cycle length was longer (p < 0.01) by less than 0.5 days in CR compared with AL rats between 3.5 and 5.5 mo of age but not different between 6.5 and 11.5 mo. Mean levels of LH in OVX rats decreased with age (p < 0.01), increased with caloric restriction (p < 0.05), and decreased with declining cycling status of the animal prior to OVX (regular [reg] vs. irregular [ir] vs. persistent estrus [pe]; p < 0.05). The increased mean LH due to caloric restriction was attributed to an increase in mean pulse amplitude and not to a decrease in time interval between LH pulses. From these data we conclude that the beneficial effects of caloric restriction on reproductive longevity may be acting at the level of the hypothalamus and/or pituitary to enhance LH secretion and do not require a delay in puberty or a period of acyclicity.

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[The below paper is not pdf-availed.]

Effect of hypocaloric normoprotein or trophic feeding versus target full enteral feeding on patient outcomes in critically ill adults: a systematic review.

Phan KA, Dux CM, Osland EJ, Reade MC.

Anaesth Intensive Care. 2017 Nov;45(6):663-675.

PMID: 29137575

Abstract

Uncertainty surrounds the optimal approach to feeding the critically ill, with increasing interest in the concept of intentional underfeeding to reduce metabolic stress while maintaining gut integrity. Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this systematic review evaluates clinical outcomes reported in studies comparing hypocaloric normonitrogenous or trophic feeding (collectively 'intentional underfeeding') targeted full energy feeding administered via enteral nutrition to adult critically ill patients. Electronic databases including PubMed, CINAHL, EMBASE and CENTRAL were searched up to September 2017 for trials evaluating intentional underfeeding versus targeted energy feeding interventions on clinical outcomes (mortality, length of stay, duration of ventilation, infective complications, feeding intolerance and glycaemic control) among critically ill adult patients. Bias of included studies was assessed using the Cochrane risk of bias tool. Of the 595 articles identified, seven studies (six randomised controlled trials, one non-randomised trial) met the inclusion criteria, representing 2,684 patients (hypocaloric normonitrogenous n=668; trophic n=681; full energy feeding n=1335). Across the studies, there was considerable heterogeneity in study methodology, population, feeding strategy and outcomes and their timepoints. We observed no evidence that intentional underfeeding, when compared to targeting full energy feeding, reduced mortality or duration of ventilation or length of stay. However, limited trial evidence is available on the impact of intentional underfeeding on post-discharge functional and quality of life outcomes.

KEYWORDS:

critical care, intensive care unit, enteral nutrition, trophic feeding, underfeeding, hypocaloric normoprotein

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Melatonin Supplementation Lowers Oxidative Stress and Regulates Adipokines in Obese Patients on a Calorie-Restricted Diet.

Szewczyk-Golec K, Rajewski P, Gackowski M, Mila-Kierzenkowska C, Wesołowski R, Sutkowy P, Pawłowska M, Woźniak A.

Oxid Med Cell Longev. 2017;2017:8494107. doi: 10.1155/2017/8494107. Epub 2017 Sep 21.

PMID: 29142618

https://www.hindawi.com/journals/omcl/2017/8494107/

Abstract

Obesity is one of the major global health problems. Melatonin deficiency has been demonstrated to correlate with obesity. The aim of the study was to estimate the effect of melatonin on oxidative stress and adipokine levels in obese patients on a calorie-restricted diet. Thirty obese patients were supplemented with a daily dose of 10 mg of melatonin (n = 15) or placebo (n = 15) for 30 days with a calorie-restricted diet. Serum levels of melatonin, 4-hydroxynonenal (HNE), adiponectin, omentin-1, leptin, and resistin, as well as erythrocytic malondialdehyde (MDA) concentration and Zn/Cu-superoxide dismutase, catalase, and glutathione peroxidase (GPx) activities, were measured at baseline and after supplementation. Significant body weight reduction was observed only in the melatonin group. After melatonin supplementation, the adiponectin and omentin-1 levels and GPx activities statistically increased, whereas the MDA concentrations were reduced. In the placebo group, a significant rise in the HNE and a drop in the melatonin concentrations were found. The results show evidence of increased oxidative stress accompanying calorie restriction. Melatonin supplementation facilitated body weight reduction, improved the antioxidant defense, and regulated adipokine secretion. The findings strongly suggest that melatonin should be considered in obesity management.

 

[it seeemed to me that the macronutritient compositions of the diets were too different to draw firm conclusions.]

Use of Novel High-Protein Functional Food Products as Part of a Calorie-Restricted Diet to Reduce Insulin Resistance and Increase Lean Body Mass in Adults: A Randomized Controlled Trial.

Johnston CS, Sears B, Perry M, Knurick JR.

Nutrients. 2017 Oct 28;9(11). pii: E1182. doi: 10.3390/nu9111182.

PMID: 29143803

http://www.mdpi.com/2072-6643/9/11/1182/htm

Abstract

Significant reductions in insulin resistance (IR) can be achieved by either calorie restriction or by the increase of lean mass. However, calorie restriction usually results in significant loss of lean mass. A 6-week randomized controlled feeding trial was conducted to determine if a calorie-restricted, high-protein diet (~125 g protein/day consumed evenly throughout the day) using novel functional foods would be more successful for reducing IR in comparison to a conventional diet (~80 g protein/day) with a similar level of calorie restriction. Healthy adults (age 20-75 years; body mass index, 20-42 kg/m²) with raised triglyceride/high-density lipoprotein ratios were randomly assigned to the control group (CON: test foods prepared using gluten-free commercial pasta and cereal) or to the high-protein group (HPR: test foods prepared using novel high-protein pasta and cereal both rich in wheat gluten). Mean weight loss did not differ between groups (-2.7 ± 2.6 and -3.2 ± 3.0 kg for CON (n = 11) and HPR (n = 10) respectively, p = 0.801); however, the 6-week change in fat-free mass (FFM) differed significantly between groups (-0.5 ± 1.5 and +1.5 ± 3.8 kg for CON and HPR respectively, p = 0.008). IR improved in HPR vs. CON participants (homeostasis model assessment-estimated insulin resistance [HOMAIR] change: -1.7 ± 1.4 and -0.7 ± 0.7 respectively; p = 0.020). The change in HOMA-IR was related to the change in FFM among participants (r = -0.511, p = 0.021). Thus, a high-protein diet using novel functional foods combined with modest calorie restriction was 140% more effective for reducing HOMA-IR in healthy adults compared to a lower protein, standard diet with an equal level of calorie restriction.

KEYWORDS:

calorie restriction; high-protein diet; insulin resistance

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Depressed Immune Responses and Accelerated Splenic Apoptosis due to Experience of Food Deprivation and Inequality but not Unstable Social Status in Balb/c Mice.

Aghajani M, Vaez Mahdavi MR, Najafabadi MK, Ghazanfari T, Moradi F, Golchoobian R, Askari H, Sanadgol N, Moghaddam EK.

Neuroimmunomodulation. 2017 Nov 17. doi: 10.1159/000480732. [Epub ahead of print]

PMID: 29145213

http://sci-hub.cc/10.1159/000480732

Abstract

OBJECTIVE(S):

We aimed to show that the immune system is sensitive to the detrimental effects of inequality and social injustice, and splenic vulnerability to apoptosis may also increase.

METHODS:

In order of better determination of immune responses to chronic social stress, we implemented food deprivation, food intake inequality, and unstable social status (a change of cage-mate every 3 days) for a period of 14 days in 60 male Balb/c mice. At the end of this stress period, nitric oxide (NO) production by peritoneal adherent cells and the serum concentration of corticosterone were measured. Moreover, the viability of peritoneal adherent cells and spleen lymphocytes was evaluated by MTT assay. The terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was done to reveal the TUNEL-reactive apoptotic bodies in the spleen.

RESULTS:

Our results showed that food deprivation and inequality caused significant changes in the apoptosis of splenic cells in comparison with the control group (p < 0.05). Moreover, the vital activities of lymphocytes and peritoneal adherent cells, as well as NO production by the latter, increased significantly (p < 0.05). However, the experience of unstable social status did not cause a further increase in the viability of lymphocytes and peritoneal adherent cells, or NO production in animals that were food-deprived or experienced inequality. Serum concentration of corticosterone in all experimental groups, except for animals that experienced unstable social status only, significantly decreased versus the control group (p < 0.05).

CONCLUSIONS:

The results suggest that poverty and social inequality, but not unstable social status, affect immune responses and are likely involved in the induction of splenic apoptosis in mice.

KEYWORDS:

Apoptosis; Food deprivation; Lymphocyte viability; Macrophages; Nitric oxide; Social inequality; Unstable social status

 

[The below paper is not pdf-availed.]

Consequences of calorie restriction and calorie excess for the physiological parameters of the yeast Saccharomyces cerevisiae cells.

Maslanka R, Kwolek-Mirek M, Zadrag-Tecza R.

FEMS Yeast Res. 2017 Nov 14. doi: 10.1093/femsyr/fox087. [Epub ahead of print]

PMID: 29145638

Abstract

Glucose plays an important role in cell metabolism and has an impact on cellular physiology. Changes in glucose availability may strongly influence growth rate of the cell size, cell metabolism and the rate of generation of cellular by-products, such as reactive oxygen species. The positive effect of low glucose concentration conditions-calorie restriction is observed in a wide range of species, including the Saccharomyces cerevisiae yeast, yet little is known about the effect of high glucose concentrations-calorie excess. Such analysis seems to be particularly important due to recently common problem of diabetes and obesity. The effect of glucose on morphological and physiological parameters of the yeast cell was conducted using genetic alteration (disruption of genes involved in glucose signalling) and calorie restriction and calorie excess conditions. The results show a significant relationship among extracellular glucose concentration, cell size and reactive oxygen species generation in yeast cells. Furthermore, the results obtained through the use of mutant strains with disorders in glucose signalling pathways suggest that the intracellular level of glucose is more important than its extracellular concentration. These data also suggest that the calorie excess as a factor which has a significant impact on cell physiology, require further comprehensive analyses.

KEYWORDS:

Saccharomyces cerevisiae; calorie excess; calorie restriction; cell size; glucose; reactive oxygen species

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The Scientist » The Nutshell

Mitochondrial Networks Explain Why Caloric Restriction Extends Worms’ Lives

By Jef Akst | November 7, 2017

https://www.the-scientist.com/?articles.view/articleNo/50886/title/Mitochondrial-Networks-Explain-Why-Caloric-Restriction-Extends-Worms--Lives/&utm_campaign=NEWSLETTER_TS_The-Scientist-Daily_2016&utm_source=hs_email&utm_medium=email&utm_content=58222658&_hsenc=p2ANqtz-8_OWS7CA1dhJydTSx4O_CGpkrsnaTxDcCV_NCJq52v7prZHNYpEFjy0EE8S2_Fep0QB4N83SoEfYIPGD-Bc119B6ElDA&_hsmi=58222658

Maintaining dynamic connections among the body’s mitochondria is required for the health and life-extending benefits of low-calorie diets for nematodes.

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

Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.

Weir HJ, Yao P, Huynh FK, Escoubas CC, Goncalves RL, Burkewitz K, Laboy R, Hirschey MD, Mair WB.

Cell Metab. 2017 Oct 23. pii: S1550-4131(17)30612-5. doi: 10.1016/j.cmet.2017.09.024. [Epub ahead of print]

PMID: 29107506

http://sci-hub.cc/10.1016/j.cmet.2017.09.024

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[sci-Hub seems to be down for a few days, so I do not know whether the below papers can be pdf-availed via Sci-Hub when and if it comes back on.]

 

Exercise training with dietary restriction enhances circulating irisin level associated with increasing endothelial progenitor cell number in obese adults: an intervention study.

Huang J, Wang S, Xu F, Wang D, Yin H, Lai Q, Liao J, Hou X, Hu M.

PeerJ. 2017 Aug 14;5:e3669. doi: 10.7717/peerj.3669. eCollection 2017.

PMID: 28828264 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560232/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560232/pdf/peerj-05-3669.pdf

Abstract

OBJECTIVE:

Circulating endothelial progenitor cells (EPCs) correlate negatively with obesity. Previous studies have shown that exercise significantly restores circulating EPC levels in obese people; however, the underlying mechanisms have not been elucidated. Recently, irisin has been reported to have a critical role in the regulation of EPCs. This exercise-induced myokine has been demonstrated to play a therapeutic role in obesity. In this study, we hypothesized that the increase in circulating irisin may form a link with increasing EPC levels in obese people after exercise.

METHODS:

Seventeen obese adults completed an 8-week program of combined exercise and dietary intervention. Clinical characteristics, blood biochemistry, and circulating irisin levels of subjects were measured before and after eight weeks of training. EPC levels were evaluated via flow cytometry, and EPC migratory and adhesive functions were also determined.

RESULTS:

Circulating irisin levels significantly increased following the 8-week training program (P < 0.05). We furthermore observed an improvement in EPC numbers (P < 0.05), and EPC migratory and adhesive functions (P < 0.001 and P < 0.05, respectively) after the intervention. Additionally, we detected a positive correlation between changes in irisin and changes in EPC number (r = 0.52, P < 0.05).

DISCUSSION:

For the first time, a positive correlation between increasing irisin levels and increasing EPC levels has been reported after an 8-week program, consisting of exercise and dietary intervention. This result suggests a novel effect of irisin on the regulation of EPC mobilization, which might contribute to improvement of endothelial function in obese people.

KEYWORDS:

Diet; Endothelial function; Endothelial progenitor cells; Exercise; Irisin; Obesity

 

Exercise training enhances in vivo clearance of endotoxin and attenuates inflammatory responses by potentiating Kupffer cell phagocytosis.

Komine S, Akiyama K, Warabi E, Oh S, Kuga K, Ishige K, Togashi S, Yanagawa T, Shoda J.

Sci Rep. 2017 Sep 20;7(1):11977. doi: 10.1038/s41598-017-12358-8.

PMID: 28931917 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607327/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607327/pdf/41598_2017_Article_12358.pdf

Abstract

The failure of Kupffer cells (KCs) to remove endotoxin is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In this study, the effects of exercise training on KC function were studied in terms of in vivo endotoxin clearance and inflammatory responses. Mice were allocated into rest and exercise groups. KC bead phagocytic capacity and plasma steroid hormone levels were determined following exercise training. Endotoxin and inflammatory cytokine levels in plasma were determined over time following endotoxin injection. KC bead phagocytic capacity was potentiated and clearance of exogenously-injected endotoxin was increased in the exercise group. Inflammatory cytokine (TNF-α and IL-6) levels were lower in the exercise group. We found that only DHEA was increased in the plasma of the exercise group. In an in vitro experiment, the addition of DHEA to RAW264.7 cells increased bead phagocytic capacity and attenuated endotoxin-induced inflammatory responses. These results suggest that exercise training modulates in vivo endotoxin clearance and inflammatory responses in association with increased DHEA production. These exercise-induced changes in KC capacity may contribute to a slowing of disease progression in NAFLD patients.

 

Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism.

Zhang J, Valverde P, Zhu X, Murray D, Wu Y, Yu L, Jiang H, Dard MM, Huang J, Xu Z, Tu Q, Chen J.

Bone Res. 2017 Feb 21;5:16056. doi: 10.1038/boneres.2016.56. eCollection 2017.

PMID: 28944087 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605767/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605767/pdf/boneres201656.pdf

Abstract

Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5 (FNDC5) protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue (WAT) and uncoupling protein 1 (UCP1) expression, leading to an increase in total body energy expenditure by augmented UCP1-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal (IP) administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

 

[The below paper is pdf-availed.]

Acute physical exercise in humans enhances reconsolidation of emotional memories.

Keyan D, Bryant RA.

Psychoneuroendocrinology. 2017 Dec;86:144-151. doi: 10.1016/j.psyneuen.2017.09.019. Epub 2017 Sep 22.

PMID: 28963883

Abstract

Increasing evidence suggests that when a memory is reactivated through retrieval, it becomes temporarily vulnerable to environmental or pharmacological manipulation, which can consequently update or strengthen the memory. Physical exercise has been shown to modulate the maintenance of fear memories in animals following memory reactivation. This study investigated the effect of intense exercise in modulating the reconsolidation of trauma memories. Fifty-four undergraduate students watched a trauma film depicting the aftermath of a highway car crash. Two days later, participants engaged in either (a) 20-25min of incremental cycling following a memory reactivation induction (Reactivation/Exercise), (b) 20-25min of mild cycling (Reactivation/No Exercise) following memory reactivation, or © 20-25min of incremental cycling but no memory reactivation (No Reactivation/Exercise). Saliva samples were collected to index salivary amylase and cortisol at baseline and post activity. Participants completed memory questionnaires relating to declarative and intrusive memory recall two days after memory reactivation. Reactivation/Exercise participants recalled more central details of the trauma film relative to other participants. Increased cortisol predicted better total memory recall in the Reactivation/Exercise, but not in the other conditions. These findings suggest that intense exercise during the period of memory reactivation enhances subsequent trauma memory, and provides human evidence consistent with recent findings of exercise-induced fear reconsolidation in animals.

KEYWORDS:

Exercise; Glucocorticoid; Memory reconsolidation; Trauma memories

 

Clinical Interventions in Aging » Volume 12

REVIEW

Does eating less make you live longer and better? An update on calorie restriction

Authors Picca A, Pesce V, Lezza AMS

Published 8 November 2017 Volume 2017:12 Pages 1887—1902

https://www.dovepress.com/does-eating-less-make-you-live-longer-and-better-an-update-on-calorie--peer-reviewed-fulltext-article-CIA

DOI https://doi.org/10.2147/CIA.S126458

Abstract: The complexity of aging is hard to be captured. However, apart from its tissue-specific features, a structural and functional progressive decline of the whole organism that leads to death, often preceded by a phase of chronic morbidity, characterizes the common process of aging. Therefore, the research goal of scientists in the field moved from the search for strategies able to extend longevity to those ensuring healthy aging associated with a longer lifespan referred to as “healthspan”. The aging process is plastic and can be tuned by multiple mechanisms including dietary and genetic interventions. To date, the most robust approach, efficient in warding off the cellular markers of aging, is calorie restriction (CR). Here, after a preliminary presentation of the major debate originated by CR, we concisely overviewed the recent results of CR treatment on humans. We also provided an update on the molecular mechanisms involved by CR and the effects on some of the age-associated cellular markers. We finally reviewed a number of tested CR mimetics and concluded with an evaluation of future applications of such dietary approach.

Keywords: aging, calorie restriction, studies on humans, CR molecular mechanisms, CR mimetics

 

Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity.

Korybalska K, Luczak J, Swora-Cwynar E, Kanikowska A, Czepulis N, Kanikowska D, Skalisz H, Breborowicz A, Grzymislawski M, Witowski J.

J Physiol Pharmacol. 2017 Aug;68(4):597-608.

PMID: 29151077

http://www.jpp.krakow.pl/journal/archive/08_17/pdf/597_08_17_article.pdf

Abstract

Endothelial cell dysfunction in obesity can be reduced by calorie restriction (CR), however it is unclear whether this benefit requires a concomitant weight loss or is it simply related to the reduced calorie intake per se. In our study serum was drawn from 41 obese women who were undergoing an 8-week dietary intervention with 15 - 30% energy deficit, and from 48 age- and sex-matched controls of normal weight. Serum was analysed for biomarkers of endothelial cell function, oxidative stress and inflammation. Compared with non-obese individuals, the obese patients had lower serum levels of nitric oxide (NO), adiponectin, and decreased serum antioxidant status. They also had significantly higher levels of adhesive molecules, thrombomodulin , von Wilebrand factor (vWF), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin. To further characterize the effect of moderate CR, the patients were ranked into two comparable groups according to the extent of weight loss - below and above the median (-5.8 kg). A moderate dietary intervention did not correct adiponectin, antioxidant status, vWF, TM, and plasminogen activator inhibitor-1 (PAI-1) but ameliorated changes in other parameters. Only changes in NO and - to a lesser degree - in sE-selectin showed a clear relationship with the magnitude of weight reduction. By contrast, a beneficial reduction in TNF-α occurred equally in patients who lost more or less weight after caloric restriction. We concluded that moderate calorie restriction could still improve several parameters of endothelial cell function irrespective of whether it was accompanied by changes in body mass. However, a significant improvement in nitric oxide, a key mediator of endothelial well-being, requires a substantial reduction in body weight.

 

[The below paper is not pdf-availed.]

Mitochondrial Intermediate Peptidase is a Novel Regulator of Sirtuin-3 Activation by Caloric Restriction.

Kobayashi M, Takeda K, Narita T, Nagai K, Okita N, Sudo Y, Miura Y, Tsumoto H, Nakagawa Y, Shimano H, Higami Y.

FEBS Lett. 2017 Nov 19. doi: 10.1002/1873-3468.12914. [Epub ahead of print]

PMID: 29151261

Abstract

Sirtuin-3 (SIRT3) regulates mitochondrial quality and is involved in the anti-aging and pro-longevity actions of caloric restriction (CR). Here, we show that CR upregulates the mature form of SIRT3 and mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase (MtSPase), in white adipose tissue. We also demonstrate that upregulation of mature SIRT3 is dependent on MIPEP in 3T3-L1 cells, suggesting that MIPEP may contribute to the maintenance of mitochondrial quality during CR via activation of SIRT3. This novel mechanism of SIRT3 activation through MIPEP facilitates the elucidation of additional molecular pathways of CR.

KEYWORDS:

caloric restriction (CR); mitochondrial intermediate peptidase (MIPEP); sirtuin-3 (SIRT3)

 

Gut microbiota composition may relate to weight loss rate in obese pet dogs.

Kieler IN, Shamzir Kamal S, Vitger AD, Nielsen DS, Lauridsen C, Bjornvad CR.

Vet Med Sci. 2017 Nov 3;3(4):252-262. doi: 10.1002/vms3.80. eCollection 2017 Nov.

PMID: 29152318

http://onlinelibrary.wiley.com/doi/10.1002/vms3.80/full

http://onlinelibrary.wiley.com/doi/10.1002/vms3.80/epdf

Abstract

Obese dogs seem to have a different gut microbiome (GM) composition compared to lean dogs, and in humans, GM composition may negatively impact the ability to lose weight in some individuals. The purpose of this study was to investigate the interaction between exercise, weight-loss and the composition of GM in dogs. Eighteen obese pet dogs were recruited for a 12-week weight-loss intervention. All dogs were fed restrictively with a commercial high-protein/high-fibre dry diet, and eight of these dogs were enrolled in an exercise program in addition to the diet intervention. Faecal samples were collected and the dogs were weighed at week 0, week 6 and week 12. GM composition was determined using MiSeq-based tag-encoded 16S rRNA gene high-throughput amplicon sequencing, and concentrations of short chain fatty acids (SCFA) by gas-liquid chromatography. Total weight loss, food allowance and GM were not changed by exercise inclusion. However, Megamonas abundance negatively correlated with weight loss rate and Ruminococcaceae relative abundance was lower at 12 weeks in dogs with a faster weight loss rate (≥1% per week) compared with slower weight loss rate (<1% per week) independent of exercise. Acetic and propionic acid concentrations decreased in the dogs with a faster weight loss rate. Members of Megamonas and Ruminococcaceae produce acetic and propionic acids and we therefore interpret that having a GM that favour SCFA production may negatively affect weight loss rate in dogs. Weight loss rate in dogs may be related to the composition of the GM and its production of metabolites.

KEYWORDS:

Canine; faecal; intestinal; microbiome; obesity; overweight; short chain fatty acids

 

[The below paper is pdf-availed.]

Role of rs1501299 variant in the adiponectin gene on total adiponectin levels, insulin resistance and weight loss after a Mediterranean hypocaloric diet.

de Luis DA, Izaola O, Primo D, Aller R.

Diabetes Res Clin Pract. 2017 Nov 14. pii: S0168-8227(17)31452-3. doi: 10.1016/j.diabres.2017.11.007. [Epub ahead of print]

PMID: 29154912

Abstract

BACKGROUND/AIM:

Several adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity. Our aim was to analyze the effects of rs1501299 ADIPOQ gene polymorphism on total adiponectin levels, insulin resistance and weight loss after a Mediterranean hypocaloric diet in obese subjects.

METHODS:

A Caucasian population of 82 obese patients was analyzed, before and after 3 months on a Mediterranean hypocaloric diet. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed.

RESULTS:

After dietary treatment and in wild type group, weight, BMI, fat mass, leptin levels, systolic blood pressure and waist circumference decreases were similar to the mutant type group. In wild type group, the decrease in total cholesterol was -28.1±15.3 mg/dl (mutant group: -12.6±16.7 mg/dl:p=0.009), LDL- cholesterol was -31.8±20.5 mg/dl (-12.2±11.5 mg/dl:p=0.006), fasting glucose plasma -4.8±2.5 mg/dL (-0.5±0.1 mg/dL:p=0.02), insulin -3.6±1.5 mUI/L (+0.6±1.1 mUI/L:p=0.02) and HOMA-IR -1.2±0.9 (-0.1±1.1:p=0.03).

CONCLUSION:

The present study suggests that T allele of ADIPO (rs1501299) could be a predictor of a lack of response of HOMA-IR, insulin, fasting glucose and LDL cholesterol secondary to a Mediterranean hypocaloric diet in obese subjects.

KEYWORDS:

Adiponectin gene; Mediterranean Diet; Rs1501299

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Caloric restriction can improve learning and memory in C57/BL mice probably via regulation of the AMPK signaling pathway.

Ma L, Wang R, Dong W, Zhao Z.

Exp Gerontol. 2017 Nov 23. pii: S0531-5565(17)30492-8. doi: 10.1016/j.exger.2017.11.013. [Epub ahead of print]

PMID: 29174968

Abstract

Caloric restriction (CR) is effective in slowing aging and delaying aging-related diseases in many species, but the mechanism is complex and not fully elucidated. This study aimed to evaluate the beneficial effects of a caloric restriction diet on learning and memory, and further to elucidate the mechanisms. Thirty 6-week-old male C57/BL mice were randomly divided into three groups: normal control (NC group), high-energy (HE group) and CR group. After 44weeks, the Morris water maze was used to examine learning and memory abilities. Western blotting and immunohistochemistry were used to detect changes in proteins involved in the adenosine monophosphate-activated protein kinase (AMPK) pathway in the mouse hippocampus. Compared with NC group, the swimming distance and escape latency were shorter in the CR group. The protein and mRNA expression of AMPK and glucose transporter type 4 (GLUT4) in the CR group were significantly higher than that in the control and HE groups. CR increased serum insulin-like growth factor, adiponectin and vaspin, decreased blood glucose and serum malondialdehyde, and improved insulin sensitivity. Our findings demonstrate that a CR diet may improve hippocampus-dependent spatial learning ability of C57/BL mice, accompanied with an increase in AMPK and GLUT4 expression, which indicates AMPK pathway was associated with the neuroprotective effect of CR in mice.

KEYWORDS:

AMPK; Caloric restriction; Insulin; Learning

 

Long-term improvement in aortic pulse wave velocity after weight loss can be predicted by white adipose tissue factors.

Bäckdahl J, Andersson DP, Eriksson-Hogling D, Caidahl K, Thorell A, Mileti E, Daub CO, Arner P, Rydén M.

Am J Hypertens. 2017 Nov 21. doi: 10.1093/ajh/hpx201. [Epub ahead of print]

PMID: 29177471

Abstract

BACKGROUND:

Arterial stiffness, measured by pulse wave velocity (PWV), is linked to obesity, cardiovascular disease and all-cause mortality. Short-term weight loss improves PWV, but the long-term effects are unknown. We investigated the effect of pronounced long-term weight loss on PWV and whether anthropometric/metabolic parameters and/or white adipose tissue (WAT) phenotype could predict this change in PWV.

METHODS:

Eighty-two obese subjects were examined before and two years after Roux-en-Y gastric bypass. Analyses included anthropometrics, routine clinical chemistry, and hyperinsulinemic-euglycemic clamp. Arterial stiffness was measured as aortic PWV (aPWV) using the Arteriograph device. WAT mass and distribution were assessed by dual- X-ray absorptiometry. Baseline visceral and subcutaneous WAT samples were obtained to measure adipocyte cell size. Transcriptomic profiling of subcutaneous WAT was performed in a subset of subjects (n = 30).

RESULTS:

At the 2-year follow-up, there were significant decreases in body mass index (39.4 ± 3.5 kg/m² vs 26.6 ± 3.4 kg/m²; p<0.0001) and aPWV (7.8 ± 1.5 m/s vs 7.2 ± 1.4 m/s; p=0.006). Multiple regression analyses showed that baseline subcutaneous adipocyte volume was associated with a reduction in aPWV (p=0.014), after adjusting for confounders. Expression analyses of 52 genes implicated in arterial stiffness showed that only one, COL4A1, independently predicted improvements in aPWV after adjusting for confounders (p=0.006).

CONCLUSIONS:

Bariatric surgery leads to long-term reduction in aPWV. This improvement can be independently predicted by subcutaneous adipocyte volume and WAT COL4A1 expression, which suggests that subcutaneous WAT has a role in regulating aPWV.

KEYWORDS:

adipocyte/metabolism; bariatric surgery; cell size; humans; longitudinal studies; morbid/complications; obesity; vascular stiffness

 

[The below paper is not pdf-availed.]

Role of pyroptosis in normal cardiac response to calorie restriction and starvation.

Wang Z, Yang F, Jiang Y, Wang R, Chen X, Lv J, Li C, Sun X, Li J, Wang S.

Biochem Biophys Res Commun. 2017 Nov 22. pii: S0006-291X(17)32323-9. doi: 10.1016/j.bbrc.2017.11.144. [Epub ahead of print]

PMID: 29175212

Abstract

AIMS:

An unhealthy diet is a major risk factor for cardiac diseases. Most researches focus on high fat diet, little is known about the detrimental effects of starvation on cardiac.

METHODS:

Mice were fed 100%, 40% and 20% of ad libitum to mimic the situation of moderate and severe caloric restriction (CR). To further evaluate the different effect of CR and starvation on cardiomyocyte, AC16 cells were treated with different concentrations of serum or glucose. TUNEL staining was performed to evaluate DNA damage in AC16 cells. HE and Masson staining were performed to detect the morphology and degree of fibrosis in myocardium from mice. Immunohistochemical staining, immunofluorescence staining, western blot and real-time PCR were used to detect the protein and mRNA expression of caspase-1, IL-1β and IL-18.

RESULTS:

CR and starvation decrease body weight of mice in a concentration dependent manner. The starvation group showed a remarkable myocardial fibrosis with no significant alteration between control and CR groups. CR inhibited the activation of caspase-1 as well as the expression of IL-1β and IL-18. On the contrary, starvation plays completely opposite effects, which was in accordance with histological changes. Similarly, different levels of serum and glucose deprivation were used to mimic the effect of CR and starvation in vitro. Moderate level of serum and glucose deprivation exerts protective effect on AC16 cells through the inhibition of pyroptosis, whereas high level of serum and glucose deprivation induces cell injury through the induction of pyroptosis.

CONCLUSION:

CR alleviates pyroptosis, whereas starvation promotes the progression of pyroptosis in myocardial tissues and cells.

KEYWORDS:

Calorie restriction; Cardiac; Pyroptosis; Starvation

 

[The below paper is not pdf-availed.]

Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high carbohydrate, low fat diet in type 2 diabetes: a 2 year randomized clinical trial.

Tay J, Thompson CH, Luscombe-Marsh ND, Wycherley TP, Noakes M, Buckley JD, Wittert GA, Yancy WS Jr, Brinkworth GD.

Diabetes Obes Metab. 2017 Nov 27. doi: 10.1111/dom.13164. [Epub ahead of print]

PMID: 29178536

Abstract

AIM:

To examine whether a low-carbohydrate, high unsaturated/low saturated fat diet (LC) improves glycemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D).

METHODS:

115 adults with T2D (mean[sD]; BMI:34.6[4.3]kg/m2 , age:58[7]yrs, HbA1c:7.3[1.1]%) were randomized to one of two planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1hr,3d/wk) for 2 years:(1) LC:14% energy as carbohydrate, 28% protein, 58% fat [<10% saturated fat]) or (2) low fat, high-carbohydrate, low glycemic index diet (HC):53% CHO, 17% protein, 30% fat [<10% saturated fat]). HbA1c, glycemic variability [GV], anti-glycemic medication effect score [MES; calculated based on the potency and dosage of the diabetes medication], weight, body composition, CVD and renal risk markers were assessed before and after intervention.

RESULTS:

Sixty-one (LC=33, HC=28) participants completed the study. Reductions in weight (estimated marginal mean [95% CI];LC:-6.8[-8.8,-4.7],HC:-6.6 [-8.8,-4.5]kg), body fat (LC:-4.3[-6.2,-2.4], HC:-4.6[-6.6,-2.7]kg), blood pressure (LC:-2.0[-5.9,1.8]/-1.2[-3.6,1.2], HC:-3.2[-7.3,0.9]/-2.0[-4.5,0.5]mmHg), HbA1c (LC:-0.6[-0.9,-0.3],HC:-0.9[-1.2,-0.5]%) and fasting glucose (LC:0.3[-0.4,1.0],HC:-0.4[-1.1,0.4]mmol/L) were similar between groups (P≥0.09). Compared to HC, the LC achieved greater reductions in diabetes medication use (MES;LC:-0.5[-0.6,-0.3],HC:-0.2[-0.4,-0.02]units;P=0.03), GV: Continuous Overall Net Glycemic Action calculated every 1-hr (LC:-0.4 [-0.6,-0.3],HC:-0.1 [-0.1,0.2]mmol/L;P=0.001), and 4-hr (LC:-0.9[-1.3,-0.6], HC:-0.2[-0.6,0.1]mmol/L;P=0.02); triglycerides (LC:-0.1[-0.3,0.2],HC:0.1[-0.2,0.3]mmol/L;P=0.001); and maintained HDL-C levels (LC:0.02[-0.05,0.1],HC:-0.1[-0.1,0.01]mmol/L;P=0.004), but had similar changes in LDL-C (LC:0.2[-0.1,0.5],HC:0.1[-0.2,0.4]mmol/L;P=0.85), brachial artery flow mediated dilatation (LC:-0.5[-1.5,0.5],HC:-0.4[-1.4,0.7]%;P=0.73), eGFR and albuminuria.

CONCLUSIONS:

Both diets achieved comparable weight loss and HbA1c reductions. The LC sustained greater reductions in diabetes medication requirements, and improvements in diurnal blood glucose stability and blood lipid profile, with no adverse renal effects, suggesting greater T2D management optimisation.

Edited by AlPater

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