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The Quest for Welfare-Friendly Feeding of Broiler Breeders: Effects of Daily vs. 5:2 Feed Restriction Schedules.

Lindholm C, Johansson A, Middelkoop A, Lees JJ, Yngwe N, Berndtson E, Cooper G, Altimiras J.

Poult Sci. 2017 Nov 22. doi: 10.3382/ps/pex326. [Epub ahead of print]

PMID: 29182752

Abstract

Restricted feeding of broiler breeders is required for improved long-term health and welfare. Because feeding frustration and hunger are major welfare concerns during rearing, many suggestions have been made to decrease the negative feelings of hunger while maintaining suitable growth rates and reproductive health. Non-daily ("skip-a-day") feeding schedules are commonly used around the world to increase portion sizes at meal times while restricting intake but these practices are prohibited in many countries due to welfare concerns on fasting days. We compared birds raised on a non-daily feeding schedule (2 non-consecutive fasting days per week, 5:2), previously suggested as a welfare-friendlier non-daily alternative, to birds raised on daily feed restriction. We found signs of increased physiological stress levels in 5:2 birds, including elevated heterophil to lymphocyte ratios (1.00 for 5:2 vs. 0.75 for daily fed at 12 weeks of age), increased adiposity (0.21% lean body weight [LBW] for 5:2 vs. 0.13% LBW for daily fed), and reduced muscle growth (pectoral muscle 5.94% LBW for 5:2 vs. 6.52% LBW for daily fed). At the same time, 5:2 birds showed signs of lower anxiety before feeding times (activity was reduced from 10.30 in daily fed to 4.85) which may be a result of the lower feed competition associated with larger portion sizes. Although we found no difference in latency to first head movement in tonic immobility between the treatments (136.5 s on average for both groups), 5:2 birds generally showed more interest in a novel object in the home pen which indicated increased risk taking and reduced fear while fasting. The 5:2 birds in this study showed no signs of learning the feeding schedule, and this unpredictability may also increase stress. Taken together, the effects of 5:2 vs. daily feed restriction on the welfare of broiler breeder pullets remain inconclusive and differ between feeding and fasting days. In addition to reducing stress by minimizing the number of fasting days, we suggest that a shift to more predictable schedules may help improve the welfare of broiler breeder pullets.

KEYWORDS:

animal welfare; broiler breeders; feed restriction; intermittent fasting; skip-a-day

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

Picca A, Pesce V, Lezza AMS.

Clin Interv Aging. 2017 Nov 8;12:1887-1902. doi: 10.2147/CIA.S126458. eCollection 2017. Review.

PMID: 29184395

https://www.crsociety.org/topic/11800-als-cr-updates/page-14?hl=pesce&do=findComment&comment=25046

 

Fasting: a major limitation for resistance exercise training effects in rodents.

das Neves W, de Oliveira LF, da Silva RP, Alves CRR, Lancha AH Jr.

Braz J Med Biol Res. 2017 Nov 17;51(1):e5427. doi: 10.1590/1414-431X20175427.

PMID: 29185588

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2018000100602

http://www.scielo.br/pdf/bjmbr/v51n1/1414-431X-bjmbr-1414-431X20175427.pdf

Abstract

Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P<0.001). After the longer RET protocol, no difference was observed for body mass, extensor digitorum longus (EDL) morphology or skeletal muscle function (P>0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01). Altogether, these data indicate that fasting is a major limitation for RET in rats.

 

[The below paper is no pdf-availed.]

Nutrient Intake During Diet-Induced Weight Loss and Exercise Interventions in a Randomized Trial in Older Overweight and Obese Adults.

Miller GD, Beavers DP, Hamm D, Mihalko SL, Messier SP.

J Nutr Health Aging. 2017;21(10):1216-1224. doi: 10.1007/s12603-017-0892-5.

PMID: 29188882

Abstract

OBJECTIVES:

Dietary restriction in obese older adults undergoing weight loss may exacerbate nutrient deficiencies common in this group; the nutritional health of older adults is a factor in their quality of life, disability, and mortality. This study examined the effect of an 18-month weight loss program based in social cognitive theory incorporating partial meal replacements, on nutrient intake in older overweight and obese adults.

DESIGN:

The following analysis is from the Intensive Diet and Exercise for Arthritis (IDEA) trial, a single-blind, randomized controlled trial. Individuals were randomized into one of three 18-month interventions: exercise (E); intensive diet-induced weight loss (D); or intensive diet-induced weight loss plus exercise (D+E).

SETTING:

The study setting was at a university research facility.

PARTICIPANTS:

Overweight and obese older adults (n=388; BMI=33.7±3.8 kg/m2; 65.8±6.1 years) were recruited.

INTERVENTIONS:

The D and D+E interventions (group mean goal of ≥10% loss by 18-months) utilized partial meal replacements (2 meal replacement shakes/day for 6-months). Exercise training for E and D+E was 3 days/week, 60 minutes/day.

MEASUREMENTS:

Three day food records were collected at baseline, 6-months, and 18-months and analyzed for total energy and macro- and micronutrient intake. Comparisons of dietary intake among treatment groups were performed at 6 and 18 months using mixed linear models.

RESULTS:

Weight loss at 18-months was 11.3±8.3% (D), 10.3±6.8% (D+E), and 1.2±4.2% (E). Meal replacements were used by more than 60% (6-months) and 50% (18-months) of D and D+E participants, compared to ≤15% for E. Both D and D+E consumed less energy and fat, and more carbohydrates and selected micronutrients than E during follow-up. More than 50% of all participants consumed less than the recommended intake of particular vitamins and minerals.

CONCLUSIONS:

The diet intervention improved intakes of several nutrients. However, inadequate intake of several vitamins and minerals of concern for older adults suggests they need further guidance to assure adequate intake.

KEYWORDS:

Diet; macronutrients; micronutrients; partial meal replacements

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Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in <i>Drosophila</i>.

Romey-Glüsing R, Li Y, Hoffmann J, von Frieling J, Knop M, Pfefferkorn R, Bruchhaus I, Fink C, Roeder T.

FASEB J. 2017 Dec 1. pii: fj.201700934R. doi: 10.1096/fj.201700934R. [Epub ahead of print]

PMID: 29196499

Abstract

Nutritional interventions such as caloric and dietary restriction increase lifespan in various animal models. To identify alternative and less demanding nutritional interventions that extend lifespan, we subjected fruit flies (Drosophila melanogaster) to weekly nutritional regimens that involved alternating a conventional diet with dietary restriction. Short periods of dietary restriction (up to 2 d) followed by longer periods of a conventional diet yielded minimal increases in lifespan. We found that 3 or more days of contiguous dietary restriction (DR) was necessary to yield a lifespan extension similar to that observed with persistent DR. Female flies were more responsive to these interventions than males. Physiologic changes known to be associated with prolonged DR, such as reduced metabolic rates, showed the same time course as lifespan extension. Moreover, concurrent transcriptional changes indicative of reduced insulin signaling were identified with DR. These physiologic and transcriptional changes were sustained, as they were detectable several days after switching to conventional diets. Taken together, diets with longer periods of DR extended lifespan concurrently with physiologic and transcriptional changes that may underlie this increase in lifespan.-Romey-Glüsing, R., Li, Y., Hoffmann, J., von Frieling, J., Knop, M., Pfefferkorn, R., Bruchhaus, I., Fink, C., Roeder, T. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

KEYWORDS:

impl2; insulin; lifespan extension; metabolic rate; sex differences

 

Whitening and Impaired Glucose Utilization of Brown Adipose Tissue in a Rat Model of Type 2 Diabetes Mellitus.

Lapa C, Arias-Loza P, Hayakawa N, Wakabayashi H, Werner RA, Chen X, Shinaji T, Herrmann K, Pelzer T, Higuchi T.

Sci Rep. 2017 Dec 1;7(1):16795. doi: 10.1038/s41598-017-17148-w.

PMID: 29196742

Abstract

Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by 18F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic 18F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. 18F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased 18F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.

 

Intermittent fasting and cardiovascular disease: current evidence and unresolved questions.

Tinsley GM, Horne BD.

Future Cardiol. 2017 Dec 4. doi: 10.2217/fca-2017-0038. [Epub ahead of print]

PMID: 29199853

Abstract

Intermittent fasting has produced a variety of beneficial health effects in animal models, although high-quality research in humans has been limited. This special report examines current evidences for intermittent fasting in humans, discusses issues that require further examination, and recommends new research that can improve the knowledge base in this emerging research area. While potentially useful for health improvement, intermittent fasting requires further study prior to widespread implementation for health purposes. Randomized, longer-term studies are needed to determine whether using intermittent fasting as a lifestyle rather than a diet is feasible and beneficial for the health of some members of the human population.

KEYWORDS:

alternate-day fasting; calorie restriction; energy restriction; fasting-mimicking diet; intermittent fasting; periodic fasting; time-restricted feeding

 

Modifications of serum levels of omentin-1 and other cardiovascular risk factors following weight loss secondary to a Mediterranean hypocaloric diet.

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

Clin Nutr. 2017 Nov 21. pii: S0261-5614(17)31407-3. doi: 10.1016/j.clnu.2017.11.009. [Epub ahead of print]

PMID: 29198435

Abstract

BACKGROUND & AIMS:

Omentin-1 might play a role on insulin resistance, dyslipidemia and obesity. The aim of this investigation was to evaluate the influence of weight loss on omentin-1 concentrations after a hypocaloric diet with Mediterranean pattern.

METHODS:

A Caucasian sample of 67 obese patients was analyzed before and after 3 months on a hypocaloric diet. Anthropometric parameters, blood pressure, fasting blood glucose, C-reactive protein (CRP), fasting insulin, insulin resistance (HOMA-IR), lipid concentrations and omentin-1 were measured.

RESULTS:

Sixty-seven obese subjects were enrolled in the study. The mean age was 48.3 ± 8.0 years (range: 25-66) and the mean BMI 34.5 ± 4.8 kg/m2 (range: 30.2-40.8). Gender distribution was 50 females (74.6%) and 17 males (25.4%). After dietary intervention and in males and females; body mass index, weight, fat mass, waist circumference, blood pressure, glucose, LDL cholesterol, insulin and HOMA-IR decreased. Omentin-1 levels increase after dietary intervention (males vs females) (delta basal vs 3 months: 10.0 ± 3.8 ng/dl: p = 0.01 vs 9.9 ± 4.1 ng/dl; p = 0.03). In the multiple regression analysis adjusted for age and sex; BMI and insulin remained independently associated with baseline and post-treatment levels of omentin-1.

CONCLUSIONS:

Our investigation showed a significant increase in omentin-1 levels after weight loss secondary to a hypocaloric diet with a Mediterranean pattern.

KEYWORDS:

Hypocaloric diet; Mediterranean diet; Obesity; Omentin-1; Weight loss

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The fat regulator neuropeptide Y and caloric restriction.

Park S, Mori R, Shimokawa I.

Aging (Albany NY). 2017 Nov 30;9(11):2243-2244. doi: 10.18632/aging.101338. No abstract available.

PMID: 29207376

http://www.aging-us.com/article/101338/text

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A key role for neuropeptide Y in lifespan extension and cancer suppression via dietary restriction.

Chiba T, Tamashiro Y, Park D, Kusudo T, Fujie R, Komatsu T, Kim SE, Park S, Hayashi H, Mori R, Yamashita H, Chung HY, Shimokawa I.

Sci Rep. 2014 Mar 31;4:4517. doi: 10.1038/srep04517.

PMID: 24682105 Free PMC Article

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970128/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970128/pdf/srep04517.pdf

Abstract

Knowledge of genes essential for the life-extending effect of dietary restriction (DR) in mammals is incomplete. In this study, we found that neuropeptide Y (Npy), which mediates physiological adaptations to energy deficits, is an essential link between DR and longevity in mice. The lifespan-prolonging effect of lifelong 30% DR was attenuated in Npy-null mice, as was the effect on the occurrence of spontaneous tumors and oxidative stress responses in comparison to wild-type mice. In contrast, the physiological processes activated during adaptation to DR, including inhibition of anabolic signaling molecules (insulin and insulin-like growth factor-1), modulation of adipokine and corticosterone levels, and preferential fatty acid oxidation, were unaffected by the absence of Npy. These results suggest a key role for Npy in mediating the effects of DR. We also provide evidence that most of the physiological adaptations to DR could be achieved in mice without Npy.

 

One year follow-up after a randomized controlled trial of a 130 g/day low-carbohydrate diet in patients with type 2 diabetes mellitus and poor glycemic control.

Sato J, Kanazawa A, Hatae C, Makita S, Komiya K, Shimizu T, Ikeda F, Tamura Y, Ogihara T, Mita T, Goto H, Uchida T, Miyatsuka T, Ohmura C, Watanabe T, Kobayashi K, Miura Y, Iwaoka M, Hirashima N, Watada H.

PLoS One. 2017 Dec 4;12(12):e0188892. doi: 10.1371/journal.pone.0188892. eCollection 2017.

PMID: 29206237

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188892

http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0188892&type=printable

Abstract

BACKGROUND & AIMS:

Recently, we conducted a prospective randomized controlled trial (RCT) showing that a 6-month 130g/day low-carbohydrate diet (LCD) reduced HbA1c and BMI more than a calorie restricted diet (CRD). [1] To assess whether the benefits of the LCD persisted after the intensive intervention, we compared HbA1c and BMI between the LCD and CRD groups at 1 year after the end of the 6-month RCT.

METHODS:

Following the end of the 6-month RCT, patients were allowed to manage their own diets with periodic outpatient visits. One year later, we analyzed clinical and nutrition data.

RESULTS:

Of the 66 participants in the original study, 27 in the CRD group and 22 in the LCD group completed this trial. One year after the end of the original RCT, the carbohydrate intake was comparable between the groups (215 [189-243]/day in the CRD group and 214 (176-262) g/day in the LCD group). Compared with the baseline data, HbA1c and BMI were decreased in both groups (CRD: HbA1c -0.4 [-0.9 to 0.3] % and BMI -0.63 [-1.20 to 0.18] kg/m2; LCD: HbA1c -0.35 [-1.0 to 0.35] % and BMI -0.77 [-1.15 to -0.12] kg/m2). There were no significant differences in HbA1c and BMI between the groups.

CONCLUSIONS:

One year after the diet therapy intervention, the beneficial effect of the LCD on reduction of HbA1c and BMI did not persist in comparison with CRD. However, combining the data of both groups, significant improvements in HbA1c and BMI from baseline were observed. Although the superiority of the LCD disappeared 1 year after the intensive intervention, these data suggest that well-constructed nutrition therapy programs, both CRD and LCD, were equally effective in improving HbA1c for at least 1 year.

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A randomized controlled trial of 130 g/day low-carbohydrate diet in type 2 diabetes with poor glycemic control.

Sato J, Kanazawa A, Makita S, Hatae C, Komiya K, Shimizu T, Ikeda F, Tamura Y, Ogihara T, Mita T, Goto H, Uchida T, Miyatsuka T, Takeno K, Shimada S, Ohmura C, Watanabe T, Kobayashi K, Miura Y, Iwaoka M, Hirashima N, Fujitani Y, Watada H.

Clin Nutr. 2017 Aug;36(4):992-1000. doi: 10.1016/j.clnu.2016.07.003. Epub 2016 Jul 18.

PMID: 27472929

Abstract

BACKGROUND & AIMS:

The usefulness of low-carbohydrate diet (LCD) for Japanese patients with type 2 diabetes mellitus (T2DM) has not been fully investigated. Therefore, we compared the effectiveness and safety of LCD with calorie restricted diet (CRD).

METHODS:

This prospective, randomized, open-label, comparative study included 66 T2DM patients with HbA1c >7.5% even after receiving repeated education programs on CRD. They were randomly allocated to either the 130g/day LCD group (n = 33) or CRD group (n = 33). Patients received personal nutrition education of CRD or LCD for 30 min at baseline, 1, 2, 4, and 6 months. Patients of the CRD group were advised to maintain the intake of calories and balance of macronutrients (28× ideal body weight calories per day). Patients of the LCD group were advised to maintain the intake of 130 g/day carbohydrate without other specific restrictions. Several parameters were assessed at baseline and 6 months after each intervention. The primary endpoint was a change in HbA1c level from baseline to the end of the study.

RESULTS:

At baseline, BMI and HbA1c were 26.5 (24.6-30.1) and 8.3 (8.0-9.3), and 26.7 (25.0-30.0) kg/m2 and 8.0 (7.6-8.9) %, in the CRD and LCD, respectively. At the end of the study, HbA1c decreased by -0.65 (-1.53 to -0.10) % in the LCD group, compared with 0.00 (-0.68 to 0.40) % in the CRD group (p < 0.01). Also, the decrease in BMI in the LCD group [-0.58 (-1.51 to -0.16) kg/m2] exceeded that observed in the CRD group (p = 0.03).

CONCLUSIONS:

Our study demonstrated that 6-month 130 g/day LCD reduced HbA1c and BMI in poorly controlled Japanese patients with T2DM. LCD is a potentially useful nutrition therapy for Japanese patients who cannot adhere to CRD. This trial was registered at http://www.umin.ac.jp/english/(University Hospital Medical Information Network: study ID number 000010663).

KEYWORDS:

Calorie-restricted diet; Low-carbohydrate diet; Type 2 diabetes

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[The below papers are pdf-availed.]

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 Dec 5;26(6):884-896.e5. doi: 10.1016/j.cmet.2017.09.024. Epub 2017 Oct 26.

PMID: 29107506

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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RevAMPing Mitochondrial Shape to Live Longer.

Pernas L, Scorrano L.

Cell Metab. 2017 Dec 5;26(6):805-806. doi: 10.1016/j.cmet.2017.11.010.

PMID: 29211978

Abstract

Whether and how mitochondria connect reduced energy intake to healthy aging are unclear. In this issue of Cell Metabolism, Weir et al. (2017) find that constitutive AMPK activation and dietary restriction promote longevity in C. elegans via remodeling of the mitochondrial network and fatty acid oxidation in peripheral tissues.

Main Text

Metabolism modulates longevity of organisms large and small. For example, caloric restriction and signaling through AMPK-activated protein kinase (AMPK), a nutrient sensor that is activated in low energy states, increase lifespan in mice and worms (Riera et al., 2016). At the core of metabolism are mitochondria, which oxidize metabolites, including pyruvate and fatty acids, to generate ATP. Changes in mitochondrial shape regulate the efficiency of fuel usage by these organelles by modulating the core components of oxidative phosphorylation (Cogliati et al., 2016). Thus, it comes as no surprise that altering mitochondrial dynamics can shorten or elongate lifespan in various model organisms. However, how mitochondrial network remodeling translates into changes in lifespan is unclear. In this issue of Cell Metabolism, Weir et al. address this gap by demonstrating that metabolic plasticity, mediated by mitochondrial fusion, is required for AMPK- and dietary restriction-mediated longevity ( Figure 1) (Weir et al., 2017).

Figure 1.

Model for Longevity Mediated by Mitochondrial Fusion and Metabolic Rewiring

Low energy states such as dietary restriction and AMPK activation require mitochondrial elongation by the outer mitochondrial fusion GTPase fzo-1 in peripheral tissues and a boost in fatty acid oxidation in mitochondria and peroxisomes to mediate lifespan extension.

The authors began by asking if the mitochondrial network remodeling previously observed in worms with constitutively active AMPK (CA-AAK-2) is necessary for the longer lifespan of these mutants (Burkewitz et al., 2015). They showed that the progressive loss of mitochondrial connectivity—a hallmark of aging in worms—is delayed in longer-lived CA-AAK-2 mutants and worms undergoing dietary restriction. When they ablated the core fusion components fzo-1 (MFN1 and 2 in mammals) and eat-3 (OPA1 in mammals), they could suppress AMPK- or dietary restriction-mediated longevity, but not when they silenced electron transport genes or a key component of insulin-like growth factor signaling (Riera et al., 2016).

Multiple tissues contribute differentially to a systemic phenotype like longevity. Indeed, neuronal crtc-1 mediates longevity in the worm, and in mammals skeletal muscle loss of the fusion protein OPA1 signals a systemic senescence cascade (Burkewitz et al., 2015 ; Tezze et al., 2017). Weir and colleagues elegantly disentangled the contribution of mitochondrial fusion to longevity in central versus peripheral tissues by driving tissue-specific mitochondrial fusion in fzo1 null;CA-AAK-2 mutants. Mitochondrial fusion was required in peripheral tissues and in the intestine for AMPK- and dietary restriction-mediated longevity, but not in neurons. This result helps separate central and peripheral control of longevity and suggests a key role for mitochondrial fusion downstream of nutrient sensing in muscles during aging.

The next logical question for Mair and colleagues was whether enhanced mitochondrial elongation by the deletion of the mitochondrial fission protein drp1 or overexpression of fzo-1 increased lifespan. Unexpectedly, contrary to the loss of drp-1 or overexpression of fzo-1, which had no impact on lifespan, the concurrent loss of both increased lifespan under normal feeding conditions. Since mitochondria adapt their morphology to functionally fit the metabolic status of the cell, the authors tested the possibility that fzo-1;drp-1 null mutants that cannot remodel their mitochondria may not live longer in conditions that require metabolic adaptation, such as fasting. Indeed, the lifespan extension observed in fzo1;drp-1 null mutants was lost when worms were fasted intermittently, supporting the idea that mitochondrial dynamics are important for organismal adaptation to changing nutrient availability.

To determine whether the metabolic state of longer-lived double null fzo-1;drp1 worms might shed light on pathways important for longevity, the authors compared the metabolic profiles of young wild-type and fzo;drp1 mutants. The metabolic profiles of fzo;drp1 mutants were consistent with increased fatty acid oxidation, a process by which fatty acids are catabolized in peroxisomes and mitochondria. This shift to increased fatty acid oxidation was crucial for the increase in longevity: chemical inhibition of mitochondrial beta-oxidation partially suppressed fzo1;drp-1 loss-mediated longevity, while genetic inhibition of peroxisomal beta-oxidation completely suppressed longevity in fzo1;drp-1 null and CA-AAK-2 mutants. Notably, the authors did not detect a common metabolic signature between young CA-AAK-2 and fzo-1;drp1 mutants and suggested that activating AMPK promotes a shift to fatty acid oxidation in older worms. A ketogenic diet that enhances fatty acid oxidation reduces midlife mortality and improves healthspan in mice (Newman et al., 2017)—would enhancing mitochondrial or peroxisomal fatty acid oxidation in worms mimic the longevity effects of AMPK activation or the deletion of fzo1 and drp1?

The work of Weir et al. has far-reaching implications regarding the consequences of mitochondrial dynamics in aging via metabolic reprogramming and opens several areas for further investigation. First, why is a delay in mitochondrial network fragmentation in CA-AAK-2 mutants sufficient to promote longevity? Since mitochondrial metabolism is intimately linked with chromatin remodeling (Sciacovelli et al., 2016), does this delay in fragmentation cause epigenetic changes that impact lifespan, analogous to what has been previously shown (Tian et al., 2016)? Another interesting question is why the total loss of fusion and fission increases lifespan in worms, but has the opposite effect in mice when ablated in cardiac tissue (Song et al., 2017). This may reflect an evolutionary divergence in the roles of mitochondrial fusion and fission in distinct tissues in mammals. Future work dissecting how organ-specific remodeling of the mitochondrial network impacts tissue communication will advance our understanding of the mechanisms by which mitochondrial dynamics impact health and aging. Lastly, the finding that the loss of fusion and fission enhances fatty acid oxidation in both mitochondria and peroxisomes is paradoxical, given the importance of mitochondrial fusion in the uptake of fatty acids from lipid droplets (Rambold et al., 2015). What are the mechanisms that underlie the rewiring of fatty acid metabolism in the absence of mitochondrial fusion and fission, and how does this translate into longer life for worms?

While much work is needed to elucidate how mitochondrial dynamics can be manipulated to extend lifespan, the identification of fatty acid oxidation as downstream of AMPK- and dietary restriction-mediated longevity by Weir et al. provides a foundation to build a better understanding of the role of metabolic rewiring in aging.

 

Central regulation of brown adipose tissue thermogenesis and energy homeostasis dependent on food availability.

Nakamura Y, Nakamura K.

Pflugers Arch. 2017 Dec 5. doi: 10.1007/s00424-017-2090-z. [Epub ahead of print] Review.

PMID: 29209779

https://link.springer.com/article/10.1007%2Fs00424-017-2090-z

Abstract

Energy homeostasis of mammals is maintained by balancing energy expenditure within the body and energy intake through feeding. Several lines of evidence indicate that brown adipose tissue (BAT), a sympathetically activated thermogenic organ, turns excess energy into heat to maintain the energy balance in rodents and humans, in addition to its thermoregulatory role for the defense of body core temperature in cold environments. Elucidating the central circuit mechanism controlling BAT thermogenesis dependent on nutritional conditions and food availability in relation to energy homeostasis is essential to understand the etiology of symptoms caused by energy imbalance, such as obesity. The central thermogenic command outflow to BAT descends through an excitatory neural pathway mediated by hypothalamic, medullary and spinal sites. This sympathoexcitatory thermogenic drive is controlled by tonic GABAergic inhibitory signaling from the thermoregulatory center in the preoptic area, whose tone is altered by body core and cutaneous thermosensory inputs. This circuit controlling BAT thermogenesis for cold defense also functions for the development of fever and psychological stress-induced hyperthermia, indicating its important role in the defense from a variety of environmental stressors. When food is unavailable, hunger-driven neural signaling from the hypothalamus activates GABAergic neurons in the medullary reticular formation, which then block the sympathoexcitatory thermogenic outflow to BAT to reduce energy expenditure and simultaneously command the masticatory motor system to promote food intake-effectively commanding responses to survive starvation. This article reviews the central mechanism controlling BAT thermogenesis in relation to the regulation of energy and thermal homeostasis dependent on food availability.

KEYWORDS:

Brown adipose tissue; Feeding; Hunger; Metabolism; Sympathetic; Thermoregulation

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[The Archives of Medical Research paper is pdf-availed.]

Optimizing Non-Pharmacologic Management of Hypertriglyceridemia.

Byrne A, Makadia S, Sutherland A, Miller M.

Arch Med Res. 2017 Dec 5. pii: S0188-4409(17)30250-3. doi: 10.1016/j.arcmed.2017.11.017. [Epub ahead of print] Review.

PMID: 29221803

Abstract

The cornerstone of initial management for hypertriglyceridemia (HTG) is lifestyle modification. The combination of weight loss through caloric restriction, alteration in macronutrient composition and increased energy expenditure reduces TG levels by approximately 50%. The addition of cinnamon, cacao products and isocaloric substitution of 1 serving of nuts may contribute another 5-15% lowering of TG. This can be particularly beneficial in patients with HTG who are at increased risk of cardiovascular disease.

KEYWORDS:

Cardiovascular disease; Diet; Lifestyle; Triglycerides; Weight loss

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Intermittent fasting and cardiovascular disease: current evidence and unresolved questions.

Tinsley GM, Horne BD.

Future Cardiol. 2017 Dec 4. doi: 10.2217/fca-2017-0038. [Epub ahead of print]

PMID: 29199853

Abstract

Intermittent fasting has produced a variety of beneficial health effects in animal models, although high-quality research in humans has been limited. This special report examines current evidences for intermittent fasting in humans, discusses issues that require further examination, and recommends new research that can improve the knowledge base in this emerging research area. While potentially useful for health improvement, intermittent fasting requires further study prior to widespread implementation for health purposes. Randomized, longer-term studies are needed to determine whether using intermittent fasting as a lifestyle rather than a diet is feasible and beneficial for the health of some members of the human population.

KEYWORDS:

alternate-day fasting; calorie restriction; energy restriction; fasting-mimicking diet; intermittent fasting; periodic fasting; time-restricted feeding

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Caloric Restriction Research: New Perspectives on the Biology of Aging.

Anderson RM, Le Couteur DG, de Cabo R.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):1-3. doi: 10.1093/gerona/glx212. No abstract available.

PMID: 29240911

 

Energy balance and the sphingosine-1-phosphate/ceramide axis.

Green C, Mitchell S, Speakman J.

Aging (Albany NY). 2017 Dec 13. doi: 10.18632/aging.101347. [Epub ahead of print] No abstract available.

PMID: 29242408

https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/zzEbzToKopC5bGMkZ.pdf

KEYWORDS:

calorie restriction; ceramide; energy balance; hunger; sphingosine-1-phosphate

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Impact of diet restriction in the management of diabetes: evidences from preclinical studies.

Krishan P, Bedi O, Rani M.

Naunyn Schmiedebergs Arch Pharmacol. 2017 Dec 16. doi: 10.1007/s00210-017-1453-5. [Epub ahead of print] Review.

PMID: 29249036

Abstract

The inappropriate dietary habits lead to the onset of age-related pathologies which include diabetes and cardiovascular ailments. Dietary restriction and nutritional therapy play an important role in the prevention of these chronic ailments. Preclinical research provides a basis for the therapeutic exploration of new dietary interventions for the clinical trials to potentiate the scientific management of diabetes and its related complications which further help in translating these nutritional improvements from bench to bedside. Within the same context, numerous therapeutically proved preclinical dietary interventions like high-fiber diet, caloric restriction, soy isoflavone-containing diets, etc., have shown the promising results for the management of diabetes and the associated complications. The focus of the present review is to highlight the various preclinical evidences of diet restriction for the management of diabetes and which will be helpful for enlightening the new ideas of nutritional therapy for future research exploration. In addition, some potential approaches are also discussed which are associated with various nutritional interventions to combat progressive diabetes and the associated disorders. Graphical abstract ᅟ.

KEYWORDS:

Caloric restriction (CR); Dietary restriction (DR); Hyperinsulinemia; Nutrition therapy

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Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: Secondary analysis of a randomized controlled trial.

Trepanowski JF, Kroeger CM, Barnosky A, Klempel M, Bhutani S, Hoddy KK, Rood J, Ravussin E, Varady KA.

Clin Nutr. 2017 Dec 5. pii: S0261-5614(17)31416-4. doi: 10.1016/j.clnu.2017.11.018. [Epub ahead of print]

PMID: 29258678

Abstract

BACKGROUND & AIMS:

Indirect comparisons suggest that alternate-day fasting (ADF) may produce greater improvements in body composition, fat distribution, and/or the adipokine profile compared to daily calorie restriction (CR), but this has not been tested directly. In a pre-planned secondary analysis of a randomized controlled trial, we compared changes in the VAT:SAT ratio, FFM:total mass ratio, and the adipokine profile between ADF and CR.

METHODS:

Overweight and obese participants (n = 100) were randomized to 1) ADF (alternating every 24-h between consuming 25% or 125% of energy needs); 2) CR (consuming 75% of needs every day); or 3) control (consuming 100% of needs every day) for 24 wk.

RESULTS:

The VAT:SAT ratio did not change in any group. The FFM:total mass ratio increased in both ADF (0.03 ± 0.00) and CR (0.03 ± 0.01) compared to the control group (P < 0.01), with no differences between the intervention groups. Circulating leptin decreased in both the ADF group (-18 ± 6%) and CR group (-31 ± 10%) relative to the control group (P < 0.05), with no differences between the intervention groups. Circulating levels of adiponectin, resistin, IL-6, and TNF-α did not change in either intervention group relative to the control group.

CONCLUSION:

ADF and CR similarly improve the FFM:total mass ratio and reduce leptin after a 24-wk intervention.

KEYWORDS:

Adipokine; Alternate day fasting; Body composition; Calorie restriction; Obese adult; Visceral adipose tissue

 

An effort toward molecular neuroeconomics of food deprivation induced food hoarding in mice: focus on xanthine oxidoreductase gene expression and xanthine oxidase activity.

Karimi I, Motamedi S, Becker LA.

Metab Brain Dis. 2017 Dec 19. doi: 10.1007/s11011-017-0166-2. [Epub ahead of print]

PMID: 29260359

Abstract

The crucial role of xanthine oxidoreductase (XOR) gene and its active isoform, xanthine oxidase (XO), in purine metabolism and cellular oxidative status led us to investigative their fluctuations in food deprivation induced food hoarding in mice. After, 10 h food deprivation, mice that hoarded lesser than 5 g were considered as 'low-hoarders' while mice that hoarded higher than 20 g were considered as 'high-hoarders'. Mice who hoarded between 5 to 20 g of food were excluded from study. An increase (1.133-fold) in encephalic XOR expression has been found in high-hoarders compared with low-hoarders without sex consideration. An increase (~ 50-fold) in encephalic XOR in female high-hoarders vs. female low-hoarders while a decrease (0.026-fold) in encephalic XOR in male high-hoarders vs. male low-hoarders demonstrated that food deprivation is associated with sex-dependent alteration in XOR expression. The encephalic and hepatic XO activities were not different in male high-hoarders vs. male low-hoarders while encephalic XO activity has been also increased significantly in female high-hoarders (~ 4 times) compared to female low-hoarders. The plasma and hepatic XO activities tended to be increased in female high-hoarders as compared to female low-hoarders, however the uric acid levels in plasma, liver and brain tissues were not altered in female high-hoarders as compared to female low-hoarders. In sum, this study generally proposed that different gene expression space is behind of hoarding behavior in a food-deprived mouse model. Specifically, this is the first study that examined the levels of encephalic XO activity and XOR expression in hoarding behavior, although additional studies are requested.

KEYWORDS:

Hoarding; Mice; Uric acid; Xanthine oxidase

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Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age.

Rusli F, Boekschoten MV, Borelli V, Sun C, Lute C, Menke AL, van den Heuvel J, Salvioli S, Franceschi C, Müller M, Steegenga WT.

Aging Cell. 2017 Dec 21. doi: 10.1111/acel.12696. [Epub ahead of print]

PMID: 29266667

http://onlinelibrary.wiley.com/doi/10.1111/acel.12696/full

http://onlinelibrary.wiley.com/doi/10.1111/acel.12696/epdf

http://onlinelibrary.wiley.com/store/10.1111/acel.12696/asset/supinfo/acel12696-sup-0001-SupInfo.pdf?v=1&s=0c9e7236f3e3d8173bfa084709dff97412247704

Abstract

Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine-week-old C57BL/6J mice were exposed either to a control, CR, or MF diet. At the age of 24 months, a subset of mice of the CR group was transferred to ad libitumMF feeding (CR-MF). The mice were sacrificed at the age of 28 months, and then, biochemical and molecular analyses were performed. Our results showed that, despite the long-term exposure to the CR regimen, mice in the CR-MF group displayed hyperphagia, rapid weight gain, and hepatic steatosis. However, no hepatic fibrosis/injury or alteration in CR-improved survival was observed in the diet switch group. The liver transcriptomic profile of CR-MF mice largely shifted to a profile similar to the MF-fed animals but leaving ~22% of the 1,578 differentially regulated genes between the CR and MF diet groups comparable with the expression of the lifelong CR group. Therefore, although the diet switch was performed at an old age, the CR-MF-exposed mice showed plasticity in coping with the challenge of a MF diet without developing severe liver pathologies.

KEYWORDS:

NAFLD ; DNA methylation; aging; glycomics; liver; long-term CR; transcriptomics

Edited by AlPater

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Effect of alternate day fasting on markers of bone metabolism: An exploratory analysis of a 6-month randomized controlled trial.

Barnosky A, Kroeger CM, Trepanowski JF, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Shapses SA, Varady KA.

Nutr Healthy Aging. 2017 Dec 7;4(3):255-263. doi: 10.3233/NHA-170031.

PMID: 29276795

Abstract

BACKGROUND:

Alternate day fasting (ADF) is a novel diet therapy that reduces body weight, but its effect on bone health remains unknown.

OBJECTIVE:

This study examined the impact of ADF versus traditional daily calorie restriction (CR) on markers of bone metabolism in a 6-month randomized controlled trial.

METHODS:

Overweight and obese subjects (n = 100) were randomized to 1 of 3 groups for 6 months: 1) ADF (25% energy intake fast day, alternated with 125% intake feast day; 2) CR (75% intake every day); or 3) control (usual intake every day).

RESULTS:

Body weight decreased similarly (P < 0.001) by ADF (-7.8±1.2%) and CR (-8.8±1.5%), relative to controls by month 6. Lean mass, total body bone mineral content and total body bone mineral density remained unchanged in all groups. Circulating osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide type I collagen (CTX) did not change in any group. IGF-1 increased (P < 0.01) in the CR group, with no change in the ADF or control group. When the data were sub-analyzed according to menopausal status, there were no differences between premenopausal or postmenopausal women for any marker of bone metabolism.

CONCLUSION:

These findings suggest that 6 months of ADF does not have any deleterious impact on markers of bone metabolism in obese adults with moderate weight loss.

KEYWORDS:

Alternate day fasting; bone metabolism; bone mineral content; bone mineral density; calorie restriction; obese adults

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Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

Dasgupta A, Kim J, Manakkadan A, Arumugam TV, Sajikumar S.

Neurobiol Learn Mem. 2017 Dec 19. pii: S1074-7427(17)30206-X. doi: 10.1016/j.nlm.2017.12.004. [Epub ahead of print]

PMID: 29277679

Abstract

Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into an improved memory formation.

KEYWORDS:

Calorie Restriction; Intermittent fasting; Metaplasticity; Synaptic Capture; Synaptic Tagging; long-term potentiation

 

Glutathione levels influence chronological life span of Saccharomyces cerevisiae in a glucose-dependent manner.

Tello-Padilla MF, Perez-Gonzalez AY, Canizal-García M, González-Hernández JC, Cortes-Rojo C, Olivares-Marin IK, Madrigal-Perez LA.

Yeast. 2017 Dec 26. doi: 10.1002/yea.3302. [Epub ahead of print]

PMID: 29277922

Abstract

Diet plays a key role in determining the longevity of the organisms since it has been demonstrated that glucose restriction increases lifespan whereas a high-glucose diet decreases it. However, the molecular basis of how diet leads to the aging process is currently unknown. We propose that the quantity of glucose that fuels respiration influences ROS generation and glutathione levels, and both chemical species impact in the aging process. Herein, we provide evidence that mutation of the gene GSH1 in S. cerevisiae diminishes glutathione levels. Moreover, glutathione levels were higher with 0.5% than in 10% glucose in the gsh1Δ and WT strains. Interestingly, the chronological life span (CLS) was lowered in the gsh1Δ strain cultured with 10% glucose but not under dietary restriction. The gsh1Δ strain also showed an inhibition of the mitochondrial respiration in 0.5 and 10% of glucose but only increased the H2 O2 levels under dietary restriction. These results correlate well with the GSH/GSSG ratio, which showed a decrease in gsh1Δ strain cultured with 0.5% glucose. Together, these data indicate that glutathione exhaustion impact negatively both the electron transport chain function and the CLS of yeast, the latter occurring when a low threshold level of this antioxidant is reached, independently of the H2 O2 levels.

KEYWORDS:

Aging; GSH; dietary restriction; glucose concentration; oxidative stress; yeast

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Quantitative Proteomic Analysis of Changes Related to Age And Calorie Restriction in Rat Liver Tissue.

Kim Y, Kwon OK, Chae S, Jung HJ, Ahn S, Jeon JM, Sung E, Kim S, Ki SH, Chung KW, Chung HY, Jung YS, Hwang DH, Lee S.

Proteomics. 2017 Dec 27. doi: 10.1002/pmic.201700240. [Epub ahead of print]

PMID: 29280565

Abstract

Calorie restriction (CR) is the most frequently studied mechanism for increasing longevity, protecting against stress, and delaying age-associated diseases. Most studies have initiated CR in young animals to determine the protective effects against aging. Although aging phenomena are well-documented, the molecular mechanisms of aging and CR remain unclear. In this study, we observed changes in hepatic proteins upon age-related and diet-restricted changes in the rat liver using quantitative proteomics. Quantitative proteomes were measured using tandem mass tag (TMT) labeling followed by liquid chromatography-tandem mass spectrometry. We compared protein levels in livers from young (6-months-old) and old (25-months-old) rats with 40% calorie-restricted (YCR and OCR, respectively) or ad libitum diets. In total, 44,279 peptides and 3,134 proteins were identified and 260 differentially expressed proteins were found. Functional enrichment analysis showed that these proteins were mainly involved in glucose and fatty acid metabolism-related processes, consistent with the theory that energy metabolism regulation is dependent on age-related and calorie-restricted changes in liver tissue. In addition, proteins mediating inflammation and gluconeogenesis were increased in OCR livers, but not YCR livers. These results showed that CR in old rats might not have anti-aging benefits because liver inflammation was increased.

KEYWORDS:

aging; caloric restriction; energy metabolism; proteomics; quantitative proteomics

 

The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans.

Honjoh S, Ihara A, Kajiwara Y, Yamamoto T, Nishida E.

Cell Rep. 2017 Dec 26;21(13):3646-3652. doi: 10.1016/j.celrep.2017.11.108.

PMID: 29281814

http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31792-8

Abstract

Organismal lifespan is highly plastic in response to environmental cues, and dietary restriction (DR) is the most robust way to extend lifespan in various species. Recent studies have shown that sex also is an important factor for lifespan regulation; however, it remains largely unclear how these two factors, food and sex, interact in lifespan regulation. The nematode Caenorhabditis elegans has two sexes, hermaphrodite and male, and only the hermaphrodites are essential for the short-term succession of the species. Here, we report an extreme sexual dimorphism in the responsiveness to DR in C. elegans; the essential hermaphrodites show marked longevity responses to various forms of DR, but the males show few longevity responses and sustain reproductive ability. Our analysis reveals that the sex determination pathway and the steroid hormone receptor DAF-12 regulate the sex-specific DR responsiveness, integrating sex and environmental cues to determine organismal lifespan.

KEYWORDS:

C. elegans; DAF-12; TRA-1; dietary restriction; gging; insulin/IGF-1-like signaling; lifespan; sex

"Female mice with lower IGF-1 signaling live longer than control mice, but male mice do not (Holzenberger et al., 2003)."

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

Nature. 2003 Jan 9;421(6919):182-7. Epub 2002 Dec 4.

IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice.

Holzenberger M, Dupont J, Ducos B, Leneuve P, Géloën A, Even PC, Cervera P, Le Bouc Y.

Abstract

Studies in invertebrates have led to the identification of a number of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signalling pathways. Examples include the related tyrosine kinase receptors InR (Drosophila melanogaster) and DAF-2 (Caenorhabditis elegans) that are homologues of the mammalian insulin-like growth factor type 1 receptor (IGF-1R). To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in mice (Igf1r). Here, using heterozygous knockout mice because null mutants are not viable, we report that Igf1r(+/-) mice live on average 26% longer than their wild-type littermates (P < 0.02). Female Igf1r(+/-) mice live 33% longer than wild-type females (P < 0.001), whereas the equivalent male mice show an increase in lifespan of 16%, which is not statistically significant. Long-lived Igf1r(+/-) mice do not develop dwarfism, their energy metabolism is normal, and their nutrient uptake, physical activity, fertility and reproduction are unaffected. The Igf1r(+/-) mice display greater resistance to oxidative stress, a known determinant of ageing. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan.

 

Special Issue: Caloric Restriction and Restrictive Diets: Interventions that Target the Biology of Aging

THE JOURNAL OF GERONTOLOGY: BIOLOGICAL SCIENCES Vol. 73, Issue 1 Pp. 1-138

https://academic.oup.com/biomedgerontology/issue

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

Caloric Restriction Research: New Perspectives on the Biology of Aging.

Anderson RM, Le Couteur DG, de Cabo R.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):1-3. doi: 10.1093/gerona/glx212. No abstract available.

PMID: 29240911

https://academic.oup.com/biomedgerontology/article/73/1/1/4733393

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

Dissociation of Striatal Dopamine and Tyrosine Hydroxylase Expression from Aging-Related Motor Decline: Evidence from Calorie Restriction Intervention.

Salvatore MF, Terrebonne J, Cantu MA, McInnis TR, Venable K, Kelley P, Kasanga EA, Latimer B, Owens CL, Pruett BS, Yu Y, Luedtke R, Forster MJ, Sumien N, Ingram DK.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):11-20. doi: 10.1093/gerona/glx119.

PMID: 28637176

https://academic.oup.com/biomedgerontology/article/73/1/11/3872273

Abstract

The escalating increase in retirees living beyond their eighth decade brings increased prevalence of aging-related impairments, including locomotor impairment (Parkinsonism) that may affect ~50% of those reaching age 80, but has no confirmed neurobiological mechanism. Lifestyle strategies that attenuate motor decline, and its allied mechanisms, must be identified. Aging studies report little to moderate loss of striatal dopamine (DA) or tyrosine hydroxylase (TH) in nigrostriatal terminals, in contrast to ~70%-80% loss associated with bradykinesia onset in Parkinson's disease. These studies evaluated the effect of ~6 months 30% calorie restriction (CR) on nigrostriatal DA regulation and aging-related locomotor decline initiated at 12 months of age in Brown-Norway Fischer F1 hybrid rats. The aging-related decline in locomotor activity was prevented by CR. However, striatal DA or TH expression was decreased in the CR group, but increased in substantia nigra versus the ad libitum group or 12-month-old cohort. In a 4- to 6-month-old cohort, pharmacological TH inhibition reduced striatal DA ~30%, comparable with decreases reported in aged rats and the CR group, without affecting locomotor activity. The dissociation of moderate striatal DA reduction from locomotor activity seen in both studies suggests that aging-related decreases in striatal DA are dissociated from locomotor decline.

KEYWORDS:

Bradykinesia; Parkinsonism; Parkinson’s disease; Striatum; Substantia nigra

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Caloric Restriction Mimetics Slow Aging of Neuromuscular Synapses and Muscle Fibers.

Stockinger J, Maxwell N, Shapiro D, deCabo R, Valdez G.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):21-28. doi: 10.1093/gerona/glx023.

PMID: 28329051

https://academic.oup.com/biomedgerontology/article/73/1/21/3063060

Abstract

Resveratrol and metformin have been shown to mimic some aspects of caloric restriction and exercise. However, it remains unknown if these molecules also slow age-related synaptic degeneration, as previously shown for caloric restriction and exercise. In this study, we examined the structural integrity of neuromuscular junctions (NMJs) in 2-year-old mice treated with resveratrol and metformin starting at 1 year of age. We found that resveratrol significantly slows aging of NMJs in the extensor digitorum longus muscle of 2-year-old mice. Resveratrol also preserved the morphology of muscle fibers in old mice. Although metformin slowed the rate of muscle fiber aging, it did not significantly affect aging of NMJs. Based on these findings, we sought to determine if resveratrol directly affects NMJs. For this, we examined postsynaptic sites, the NMJ region located on the muscle peripheral membrane, on cultured myotubes derived from C2C12 cells. We discovered that resveratrol increases the number of postsynaptic sites on myotubes exhibiting a youthful architecture, suggesting that resveratrol directly affects the NMJ. Altogether, we provide compelling evidence indicating that resveratrol slows aging of NMJs and muscle fibers.

KEYWORDS:

Metabolism; Metformin; Myotube; NMJ; Resveratrol

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Caloric Restriction and Rapamycin Differentially Alter Energy Metabolism in Yeast.

Choi KM, Hong SJ, van Deursen JM, Kim S, Kim KH, Lee CK.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):29-38. doi: 10.1093/gerona/glx024.

PMID: 28329151

https://academic.oup.com/biomedgerontology/article/73/1/29/3063959

Abstract

Rapamycin (RM), a drug that inhibits the mechanistic target of rapamycin (mTOR) pathway and responds to nutrient availability, seemingly mimics the effects of caloric restriction (CR) on healthy life span. However, the extent of the mechanistic overlap between RM and CR remains incompletely understood. Here, we compared the impact of CR and RM on cellular metabolic status. Both regimens maintained intracellular ATP through the chronological aging process and showed enhanced mitochondrial capacity. Comparative transcriptome analysis showed that CR had a stronger impact on global gene expression than RM. We observed a like impact on the metabolome and identified distinct metabolites affected by CR and RM. CR severely reduced the level of energy storage molecules including glycogen and lipid droplets, whereas RM did not. RM boosted the production of enzymes responsible for the breakdown of glycogen and lipid droplets. Collectively, these results provide insights into the distinct energy metabolism mechanisms induced by CR and RM, suggesting that these two anti-aging regimens might extend life span through distinctive pathways.

KEYWORDS:

Metabolomics; Transcriptomics

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Telomeres, Nutrition, and Longevity: Can We Really Navigate Our Aging?

Vidacek NŠ, Nanic L, Ravlic S, Sopta M, Geric M, Gajski G, Garaj-Vrhovac V, Rubelj I.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):39-47. doi: 10.1093/gerona/glx082. Review.

PMID: 28510637

https://academic.oup.com/biomedgerontology/article/73/1/39/3828300

Abstract

Telomeres are dynamic chromosome-end structures that serve as guardians of genome stability. They are known to be one of the major determinants of aging and longevity in higher mammals. Studies have demonstrated a direct correlation between telomere length and life expectancy, stress, DNA damage, and onset of aging-related diseases. This review discusses the most important factors that influence our telomeres. Various genetic and environmental factors such as diet, physical activity, obesity, and stress are known to influence health and longevity as well as telomere dynamics. Individuals currently have the opportunity to modulate the dynamics of their aging and health span, monitor these processes, and even make future projections by following their telomere dynamics. As telomeres react to positive as well as negative health factors, we should be able to directly influence our telomere metabolism, slow their deterioration, and diminish our aging and perhaps extend our life and health span.

KEYWORDS:

Dietary restriction; Human aging; Longevity; Telomeres

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Caloric Restriction Study Design Limitations in Rodent and Nonhuman Primate Studies.

Vaughan KL, Kaiser T, Peaden R, Anson RM, de Cabo R, Mattison JA.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):48-53. doi: 10.1093/gerona/glx088.

PMID: 28977341

https://academic.oup.com/biomedgerontology/article/73/1/48/3867389

Abstract

For a century, we have known that caloric restriction influences aging in many species. However, only recently it was firmly established that the effect is not entirely dependent on the calories provided. Instead, rodent and nonhuman primate models have shown that the rate of aging depends on other variables, including the macronutrient composition of the diet, the amount of time spent in the restricted state, age of onset, the gender and genetic background, and the particular feeding protocol for the control group. The field is further complicated when attempts are made to compare studies across different laboratories, which seemingly contradict each other. Here, we argue that some of the contradictory findings are most likely due to methodological differences. This review focuses on the four methodological differences identified in a recent comparative report from the National Institute on Aging and University of Wisconsin nonhuman primate studies, namely feeding regimen, diet composition, age of onset, and genetics. These factors, that may be influencing the effects of a calorie restriction intervention, are highlighted in the rodent model to draw parallels and elucidate findings reported in a higher species, nonhuman primates.

KEYWORDS:

Calorie restriction; Dietary restriction; Monkey; Rodent; Translational

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Taking Obesity in Older Adults Seriously.

Kritchevsky SB.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):57-58. doi: 10.1093/gerona/glx228. No abstract available.

PMID: 29240912

https://academic.oup.com/biomedgerontology/article/73/1/57/4733394

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Very Low Calorie Diets for Weight Loss in Obese Older Adults-A Randomized Trial.

Haywood CJ, Prendergast LA, Purcell K, Le Fevre L, Lim WK, Galea M, Proietto J.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):59-65. doi: 10.1093/gerona/glx012.

PMID: 28329121

https://academic.oup.com/biomedgerontology/article/73/1/59/3038156

Abstract

BACKGROUND:

Obesity contributes to disability in older adults, and this is offset by weight loss and exercise. Very Low Calorie Diets (VLCDs) achieve rapid weight loss; however, these have not been rigorously evaluated in older people.

METHODS:

A randomized trial was conducted from August 2012 through December 2015. The intervention was 12 weeks of thrice weekly exercise combined with either healthy eating advice (Ex/HE), hypocaloric diet (Ex/Diet), or VLCD (Ex/VLCD). Outcomes were physical function, measured by 6-minute walk test (6MWT) and De Morton Mobility Index (DEMMI). Other measures were body composition measured by Dual Energy X-Ray Absorptiometry, and nutritional parameters (albumin, vitamins B12 and D, ferritin and folate).

RESULTS:

36, 40, and 41 participants were randomized to Ex/HE, Ex/Diet, and Ex/VLCD, respectively. At 12 weeks, weight was reduced by 3.7, 5.1, and 11.1% (p < .01), respectively. Ex/VLCD had significant reduction in fat (16.8%), lean mass (4.8%), and bone mineral density (1.2%), but increased relative lean mass (3.8%). DEMMI improved by 14.25, 14.25, and 13.75 points in Ex/HE, Ex/Diet, and Ex/VLCD, respectively; however, there was no between-group difference (p = .30). 6MWT improved by 53.1, 64.7, and 84.4 meters in Ex/HE, Ex/Diet, and Ex/VLCD (p = .18). Post hoc stratification for gender and adjustment for initial physical function and type 2 diabetes only revealed significant between-group differences for men in the 6MWT, with improvement by 57.8, 77.8, and 140.3 meters in Ex/HE, Ex/Diet, and Ex/VLCD, respectively (p = .01). Improvements in nutritional parameters were seen in Ex/VLCD, but not in Ex/HE and Ex/Diet. The VLCD was well tolerated.

CONCLUSIONS:

VLCDs have potential in the treatment of obesity in older persons; of particular benefit is improvement in nutritional status. The gait speed improvement observed in men warrants further investigation.

KEYWORDS:

Aged; Body composition; Obesity; Physical function; Very low calorie diet

 

Effects of Calorie Restriction in Obese Older Adults: The CROSSROADS Randomized Controlled Trial.

Ard JD, Gower B, Hunter G, Ritchie CS, Roth DL, Goss A, Wingo BC, Bodner EV, Brown CJ, Bryan D, Buys DR, Haas MC, Keita AD, Flagg LA, Williams CP, Locher JL.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):73-80. doi: 10.1093/gerona/glw237.

PMID: 28003374

https://academic.oup.com/biomedgerontology/article/73/1/73/2731238

Abstract

BACKGROUND:

We lack a comprehensive assessment of the risks and benefits of calorie restriction in older adults at high risk for cardiometabolic disease. Calorie restriction may reduce visceral adipose tissue (VAT) but also have negative effects on lean mass and quality of life.

METHODS:

We conducted a 52-week, randomized controlled trial involving 164 older adults with obesity taking at least one medication for hyperlipidemia, hypertension, or diabetes. Interventions included an exercise intervention alone (Exercise), or with diet modification and body weight maintenance (Maintenance), or with diet modification and energy restriction (Weight Loss). The primary outcome was change in VAT at 12 months. Secondary outcomes included cardiometabolic risk factors, functional status, and quality of life.

RESULTS:

A total of 148 participants had measured weight at 12 months. Despite loss of -1.6% ± 0.3% body fat and 4.1% ± 0.7% initial body weight, Weight Loss did not have statistically greater loss of VAT (-192.6 ± 185.2 cm3) or lean mass (-0.4 ± 0.3 kg) compared with Exercise (VAT = -21.9 ± 173.7 cm3; lean mass = 0.3 ± 0.3 kg). Quality of life improved in all groups with no differences between groups. No significant changes in physical function were observed. Weight Loss had significantly greater improvements in blood glucose (-8.3 ± 3.6 mg/dL, p < .05) and HDL-cholesterol (5.3 ± 1.9, p < .01) compared with Exercise. There were no group differences in the frequency of adverse events.

CONCLUSIONS:

While moderate calorie restriction did not significantly decrease VAT in older adults at high risk for cardiometabolic disease, it did reduce total body fat and cardiometabolic risk factors without significantly more adverse events and lean mass loss.

KEYWORDS:

Weight reduction; cardiometabolic risk; physical function; quality of life; visceral adipose tissue

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

Calorie Restriction-induced Weight Loss and Exercise Have Differential Effects on Skeletal Muscle Mitochondria Despite Similar Effects on Insulin Sensitivity.

Menshikova EV, Ritov VB, Dube JJ, Amati F, Stefanovic-Racic M, Toledo FGS, Coen PM, Goodpaster BH.

J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):81-87. doi: 10.1093/gerona/glw328.

PMID: 28158621

https://academic.oup.com/biomedgerontology/article/73/1/81/2966367

Abstract

BACKGROUND:

Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals.

METHODS:

Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions.

RESULTS:

Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin.

CONCLUSION:

Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults.

KEYWORDS:

Caloric restriction; Glucose uptake; Human aging; Muscle metabolism; Obesity

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Sirtuins in Brain Aging and Neurological Disorders.

Qadir MI, Anwar S.

Crit Rev Eukaryot Gene Expr. 2017;27(4):321-329. doi: 10.1615/CritRevEukaryotGeneExpr.2017019532.

PMID: 29283326

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357501/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357501/pdf/11064_2016_Article_2110.pdf

Abstract

The many ways of aging have been and continue to be investigated. For this reason, over many years, several studies have resolved some of the genetic details underlying aging processes. It resulted in the identification of a yeast gene known as Sir2, which is a longevity modulator. Sir2 and SIRT1 are the mammalian homologs of yeast genes. Sirtuins (including SIRT1) play an important role in aging of the brain and the metabolic regulation pathway in mammals. Aging in the brain is caused by the loss of neurophysiologic functions due to neurodegeneration. The sirtuin family plays a central role in the beneficial effects of calorie restriction (CR). CR is linked with an increase in life span and decrease in the risk of diseases related to the brain. Sirtuins may be helpful for us in studying the process of aging and treatment of diseases related with aging.

 

Food restriction during pregnancy and female offspring fertility: adverse effects of reprogrammed reproductive lifespan.

Harrath AH, Alrezaki A, Mansour L, Alwasel SH, Palomba S.

J Ovarian Res. 2017 Dec 28;10(1):77. doi: 10.1186/s13048-017-0372-x.

PMID: 29282125

Abstract

BACKGROUND:

Food restriction during pregnancy can influence the health of the offspring during the adulthood. The aim of the present study was to examine the effect of maternal food restriction (MFR) on the reproductive performance in female rat offspring from the first (FR1) and second (FR2) generations.

METHODS:

Adult virgin Wistar female rats were given free access to tap water and were fed ad libitum on standard rodent chow, were mated with virgin adult males, and then were randomly divided into two groups: controls (that was fed ad libitum ) and food-restricted group (FR, that was given only 50% of ad libitum food throughout gestation). Their first (FR1) and the second (FR2) generation of offspring were fed ad libitum and sacrificed before puberty and at adulthood. Their ovaries were removed and their histology evaluated by estimating the number of follicles (total and at various stages of folliculogenesis), and the presence of multi-nuclei oocytes and multi-oocyte follicles.

RESULTS:

Total number of ovarian follicles was lower in FR1 females at week 4 in comparison with controls, while it was not different in FR2 females vs.

CONTROLS:

The number of the primordial follicle was lower in FR1 and FR2 females vs. controls at both week 4 and at week 8. When compared to the controls, the follicles containing multi-nuclei oocytes were more frequent in ovaries from FR1 and FR2 females at week 4, and higher and lower respectively in ovaries form FR1 and FR2 females at week 8.

CONCLUSION:

MFR affects ovarian histology by inducing the development of abnormal follicles in the ovaries in first and second generation offspring. This finding could influence the ovarian function resulting in an early pubertal onset and an early decline in reproductive lifespan.

KEYWORDS:

Follicle; Food restriction; Oocyte; Ovary; Pregnancy

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Cellular and Molecular Mechanisms Underlying Non-Pharmaceutical Ischemic Stroke Therapy in Aged Subjects.

Sandu RE, Dumbrava D, Surugiu R, Glavan DG, Gresita A, Petcu EB.

Int J Mol Sci. 2017 Dec 29;19(1). pii: E99. doi: 10.3390/ijms19010099. Review.

PMID: 29286319

Abstract

The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H₂S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory.

CONCLUSION:

animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects.

KEYWORDS:

ageing; calorie restriction; cerebral ischemia; hypothermia; inflammation; obesity

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Effects of 5-HT and insulin on learning and memory formation in food-deprived snails.

Aonuma H, Totani Y, Kaneda M, Nakamura R, Watanabe T, Hatakeyama D, Dyakonova VE, Lukowiak K, Ito E.

Neurobiol Learn Mem. 2017 Dec 30. pii: S1074-7427(17)30218-6. doi: 10.1016/j.nlm.2017.12.010. [Epub ahead of print]

PMID: 29294381

Abstract

The pond snail Lymnaea stagnalis learns conditioned taste aversion (CTA) and consolidates it into long-term memory (LTM). How well they learn and form memory depends on the degree of food deprivation. Serotonin (5-HT) plays an important role in mediating feeding, and insulin enhances the memory consolidation process following CTA training. However, the relationship between these two signaling pathways has not been addressed. We measured the 5-HT content in the central nervous system (CNS) of snails subjected to different durations of food deprivation. One-day food-deprived snails, which exhibit the best learning and memory, had the lowest 5-HT content in the CNS, whereas 5-day food-deprived snails, which do not learn, had a high 5-HT content. Immersing 1-day food-deprived snails in 5-HT impaired learning and memory by causing an increase in 5-HT content, and that the injection of insulin into these snails reversed this impairment. We conclude that insulin rescues the CTA deficit and this may be due to a decrease in the 5-HT content in the CNS of Lymnaea.

KEYWORDS:

Lymnaea; conditioned taste aversion; feeding; food-deprivation; insulin; serotonin

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Analysis of Polymorphisms in 58 Potential Candidate Genes for Association with Human Longevity.

Donlon TA, Morris BJ, Chen R, Masaki KH, Allsopp RC, Willcox DC, Tiirikainen M, Willcox BJ.

J Gerontol A Biol Sci Med Sci. 2017 Dec 30. doi: 10.1093/gerona/glx247. [Epub ahead of print]

PMID: 29300832

Abstract

Longevity is a polygenic trait in which genetic predisposition is particularly important. We hypothesized that amongst genes differentially expressed in response to caloric restriction, several may be candidate longevity genes. We tested 459 single nucleotide polymorphisms (SNPs) in 46 genes differentially expressed in calorically-restricted mice and 12 other genes for association with longevity. Subjects were American men of Japanese ancestry, 440 aged ≥95 years and 374 with an average lifespan. Based on a dominant model of inheritance, an association with longevity at the p < 0.05 level was seen for SNPs in 13 of the genes. Testing by all possible models increased the number of genes to 18. After correction for multiple testing, 4 genes retained significance, namely, MAP3K5 (p=0.00004), SIRT7 (p=0.00004), SIRT5 (p=0.0007), and PIK3R1 (p=0.01). In a dominant model, association with longevity was seen for multiple adjacent SNPs within two of these genes (MAP3K5 and PIK3R1), as well as in FLT1, consistent with linkage disequilibrium with a causative variant in the vicinity of each respective SNP set. MAP3K5 and FLT1 haplotypes were associated with longevity. In conclusion, the present study implicates variation in MAP3K5, FLT1, PIK3R1, SIRT7 and SIRT5 in human longevity.

KEYWORDS:

Caloric restriction; Human genetics; Longevity; Quantitative genetics

 

Is it Time to State That Diet Restriction Does Not Increase Life span in Primates?

Le Bourg E.

J Gerontol A Biol Sci Med Sci. 2017 Dec 28. doi: 10.1093/gerona/glx159. [Epub ahead of print] No abstract available.

PMID: 29300833

Vaughan et al. (1) have published an article in this journal to explain why the two studies on diet restriction in macaques have provided very different results: no life-span increase in the diet-restricted group in Mattison et al. (2), and an increase in Colman et al. (3,4). The differences between the two studies have been stressed (5,6). Particularly, the control group of Colman et al. (3,4) was fed ad libitum a “typical Western modern diet rich in refined and processed foods” (5). A diet “more similar to the traditional Mediterranean or Japanese diet” (5) was portioned to prevent obesity in the control group of Mattison...

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Intermittent fasting protects against the deterioration of cognitive function, energy metabolism and dyslipidemia in Alzheimer's disease-induced estrogen deficient rats.

Shin BK, Kang S, Kim DS, Park S.

Exp Biol Med (Maywood). 2018 Jan 1:1535370217751610. doi: 10.1177/1535370217751610. [Epub ahead of print]

PMID: 29307281

Abstract

Intermittent fasting may be an effective intervention to protect against age-related metabolic disturbances, although it is still controversial. Here, we investigated the effect of intermittent fasting on the deterioration of the metabolism and cognitive functions in rats with estrogen deficiency and its mechanism was also explored. Ovariectomized rats were infused with β-amyloid (25-35; Alzheimer's disease) or β-amyloid (35-25, Non-Alzheimer's disease; normal cognitive function) into the hippocampus. Each group was randomly divided into two sub-groups: one with intermittent fasting and the other fed ad libitum: Alzheimer's disease-ad libitum, Alzheimer's disease-intermittent fasting, Non-Alzheimer's disease-ad libitum, and Non-Alzheimer's disease-intermittent fasting. Rats in the intermittent fasting groups had a restriction of food consumption to a 3-h period every day. Each group included 10 rats and all rats fed a high-fat diet for four weeks. Interestingly, Alzheimer's disease increased tail skin temperature more than Non-Alzheimer's disease and intermittent fasting prevented the increase. Alzheimer's disease reduced bone mineral density in the spine and femur compared to the Non-Alzheimer's disease, whereas bone mineral density in the hip and leg was reduced by intermittent fasting. Fat mass only in the abdomen was decreased by intermittent fasting. Intermittent fasting decreased food intake without changing energy expenditure. Alzheimer's disease increased glucose oxidation, whereas intermittent fasting elevated fat oxidation as a fuel source. Alzheimer's disease and intermittent fasting deteriorated insulin resistance in the fasting state but intermittent fasting decreased serum glucose levels after oral glucose challenge by increasing insulin secretion. Alzheimer's disease deteriorated short and spatial memory function compared to the Non-Alzheimer's disease, whereas intermittent fasting prevented memory loss in comparison to ad libitum. Unexpectedly, cortisol levels were increased by Alzheimer's disease but decreased by intermittent fasting. Intermittent fasting improved dyslipidemia and liver damage index compared to ad libitum. Alzheimer's disease lowered low-density lipoprotein cholesterol and serum triglyceride levels compared to Non-Alzheimer's disease. In conclusion, Alzheimer's disease impaired not only cognitive function but also disturbed energy, glucose, lipid, and bone metabolism in ovariectomized rats. Intermittent fasting protected against the deterioration of these metabolic parameters, but it exacerbated bone mineral density loss and insulin resistance at fasting in Alzheimer's disease-induced estrogen-deficient rats.

Impact statement

Intermittent fasting was evaluated for its effects on cognitive function and metabolic disturbances in a rat model of menopause and Alzheimer's disease. Intermittent fasting decreased skin temperature and fat mass, and improved glucose tolerance with decreasing food intake. Intermittent fasting also prevented memory loss: short-term and special memory loss. Therefore, intermittent fasting may prevent some of the metabolic pathologies associated with menopause and protect against age-related memory decline.

KEYWORDS:

Intermittent fasting; bone mineral density; dyslipidemia; glucose tolerance; insulin resistance; memory loss

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Comparison of Calorie-Restricted Diet and Resveratrol Supplementation on Anthropometric Indices, Metabolic Parameters, and Serum Sirtuin-1 Levels in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial.

Asghari S, Asghari-Jafarabadi M, Somi MH, Ghavami SM, Rafraf M.

J Am Coll Nutr. 2018 Jan 9:1-11. doi: 10.1080/07315724.2017.1392264. [Epub ahead of print]

PMID: 29313746

Abstract

OBJECTIVE:

There is a promising perspective regarding the potential effect of resveratrol in preventing and treating metabolic disturbances similar to that of calorie restriction. The aim of this study was to evaluate the effects of calorie-restricted (CR) diet on metabolic parameters and then to investigate whether resveratrol supplementation has beneficial effects similar to CR diet in patients with nonalcoholic fatty liver disease (NAFLD).

METHODS:

This randomized controlled clinical trial was conducted in 90 patients with NAFLD (males and females) aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were assigned to one of three intervention groups as follows: The CR diet group (n = 30) received a prescribed low-calorie diet, the resveratrol group (n = 30) received 600 mg pure trans-resveratrol (2 × 300 mg) daily, and the placebo group (n = 30) received placebo capsules (2 × 300 mg) daily for 12 weeks. Fasting blood samples, anthropometric measurements, and dietary intake and physical activity data were collected for all participants at baseline and at the end of the trial.

RESULTS:

CR diet significantly reduced weight (by 4.5%); BMI; waist circumference; waist-to-hip ratio; and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles in participants compared to resveratrol and placebo (all p < 0.05). Significant reductions in weight (by 1.1%) and BMI were found in the resveratrol group compared to the placebo group (p < 0.05). ALT, AST, and lipid profiles did not change significantly in the resveratrol group (all p > 0.05). No significant changes were seen in hepatic steatosis grade, serum glycemic parameters, and high-density lipoprotein cholesterol and sirtuin-1 levels in any group (all p > 0.05).

CONCLUSIONS:

CR diet with moderate weight loss has favorable effects on NAFLD, and resveratrol supplementation induced weight loss but failed to mimic other aspects of CR diet. Future studies are warranted to evaluate the long-term and dose-dependent effects of resveratrol on metabolic diseases.

KEYWORDS:

Calorie restriction; clinical trial; nonalcoholic fatty liver disease; resveratrol; sirtuin-1

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GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose.

Iwasaki Y, Sendo M, Dezaki K, Hira T, Sato T, Nakata M, Goswami C, Aoki R, Arai T, Kumari P, Hayakawa M, Masuda C, Okada T, Hara H, Drucker DJ, Yamada Y, Tokuda M, Yada T.

Nat Commun. 2018 Jan 9;9(1):113. doi: 10.1038/s41467-017-02488-y.

PMID: 29317623

Abstract

Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance. These effects are blunted by vagotomy or pharmacological GLP-1R blockade, and by genetic inactivation of GLP-1R signaling in whole body or selectively in vagal afferents. Our results identify D-allulose as prominent GLP-1 releaser that acts via vagal afferents to restrict feeding and hyperglycemia. Furthermore, when administered in a time-specific manner, chronic D-allulose corrects arrhythmic overeating, obesity and diabetes, suggesting that chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.

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[The below paper is pdf-availed.]

Intermittent metabolic switching, neuroplasticity and brain health.

Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A.

Nat Rev Neurosci. 2018 Jan 11. doi: 10.1038/nrn.2017.156. [Epub ahead of print] Review.

PMID: 29321682

Abstract

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease.

"Key points

Brain evolution, including higher cortical functions of humans (imagination, creativity and language), was driven by the necessity of sustaining high levels of performance in a food-deprived (fasted) state

Intermittent metabolic switching (IMS) occurs when eating and exercise patterns result in periodic depletion of liver glycogen stores and the associated production of ketones from fatty acids. IMS occurs rarely or not at all in individuals who eat three or more meals per day and who are fairly sedentary

The ketone β-hydroxybutyrate (BHB) is transported into the brain and into neuronal mitochondria, where it is used to generate acetyl CoA and ATP. BHB also acts as a signalling molecule in neurons that can induce the expression of brain-derived neurotrophic factor and thereby promote synaptic plasticity and cellular stress resistance

During fasting and extended exercise, adaptive cellular stress-response signalling pathways are activated and autophagy is stimulated, whereas overall protein synthesis is reduced. Upon refeeding, rest and sleep, protein synthesis is upregulated and mitochondrial biogenesis occurs, enabling neurogenesis and synaptogenesis

IMS can enhance cognition and motor performance and protects neurons against dysfunction and degeneration in animal models of stroke, epilepsy, traumatic brain and spinal cord injury, Alzheimer disease and Parkinson disease

Intermittent fasting can improve indicators of metabolic and cardiovascular health in humans by mechanisms involving reductions in oxidative damage and inflammation. However, it remains to be determined whether and how intermittent fasting impacts the brains of healthy humans and those affected with a neurological disorder

Introduction

Food scarcity has been a driving force for the evolution of nervous systems; indeed, even the most advanced capabilities of the human brain (imagination, creativity and language) arose via selection for individuals who were adept at cooperating to acquire and share food1,2,3. However, people in modern societies typically consume food three or more times each day. Every time they eat, the glycogen stores in their liver are replenished; liver glycogen provides 700–900 calories of glucose or energy, an amount that will last 10–14 hours in individuals who are not exercising. Subsequently, liver energy stores are depleted, circulating glucose levels remain low and adipose cells release fatty acids, which are converted in the liver to the ketone bodies β-hydroxybutyrate (BHB) and acetoacetate (AcAc), which are released into the blood and are used as energy substrates by neurons4,5 (Fig. 1). The transition from utilization of carbohydrates and glucose to fatty acids and ketones as the major cellular fuel source can be referred to as the 'G-to-K switch'. Upon consumption of food after a fast, the major energy source for cells switches back to glucose ('K-to-G switch'). Because exercise accelerates the depletion of liver glycogen stores, it hastens the onset of the G-to-K switch. For example, the metabolic switch may occur in someone who runs for 1 hour (during which time they use approximately 600 calories) beginning 4 hours after their most recent meal."

"Conclusions and future directions

The evidence reviewed in this article leads to several general conclusions regarding IMS and neuroplasticity. First, cognition, sensory–motor function and physical performance can be enhanced by IMS protocols involving IF and/or vigorous exercise. Second, by providing an alternative energy source and activating signalling pathways involved in neuroplasticity and cellular stress resistance, the ketone BHB plays a particularly important role in neuronal adaptations to fasting and exercise. Third, neurons respond to the G-to-K switch by engaging a 'cell-preservation mode' and adopt a 'cell-growth mode' by activation of certain signalling pathways when the switch is off (food, rest and sleep). Fourth, fasting and exercise upregulate neurotrophic factor signalling, antioxidant and DNA repair enzymes, protein deacetylases and autophagy, which protects neurons against stress and sets the stage for mitochondrial biogenesis and cell growth and plasticity during recovery periods (Fig. 3). Fifth, lifestyles characterized by little or no IMS (three meals per day plus snacks and negligible exercise) result in suboptimal brain functionality and increase the risk of major neurodegenerative and psychiatric disorders. Sixth, many different IMS regimens are likely to improve brain health such that individuals may choose an approach that suits their particular daily and weekly schedules."

 

[The below paper is pdf-availed.]

The association of SNP276G>T at adiponectin gene with insulin resistance and circulating adiponectin in response to two different hypocaloric diets.

de Luis DA, Izaola O, Primo D, Aller R, Ortola A, Gómez E, Lopez JJ.

Diabetes Res Clin Pract. 2018 Jan 8. pii: S0168-8227(17)31198-1. doi: 10.1016/j.diabres.2018.01.003. [Epub ahead of print]

PMID: 29325772

Abstract

BACKGROUND:

Several adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity.

OBJECTIVE:

The aim of our study was to analyze the effect of rs1501299 ADIPOQ gene polymorphism and dietary intake on total adiponectin levels and insulin resistance after two hypocaloric diets in obese subjects.

MATERIAL AND METHODS:

A Caucasian population of 284 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets (I: moderate carbohydrates vs II: low fat). Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild) (dominant model).

RESULTS:

The genotype distribution was 149 GG, 124 GT and 21 TT. With caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure, total LDL cholesterol, LDL cholesterol and leptin levels decreased. Only in subjects with GG genotype, diet I and II decreased fasting insulin levels, HOMA-IR and adiponectin levels. The improvement was similar with both diets; insulin concentrations (Diet I: -4.7±1.4 mUI/L vs. Diet II: -5.9±1.9 mUI/L:p=0.76), HOMA-IR (Diet I: -1.4±0.6 units vs. Diet II: -2.0±0.7 units:p=0.56) and adiponectin levels (Diet I: -10.2±3.4 ng/dl vs. Diet II: -14.0±2.9 ng/dl:p=0.33).

CONCLUSION:

The GG genotype of ADIPOQ gene variant (rs1501299) is associated with an increase in adiponectin levels and a decrease of insulin and HOMA-IR after weight loss.

KEYWORDS:

ADIPOQ; Hypocaloric diets; SNP276G>T; adiponectin; insulin resistance; weight loss

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Omega-3 fatty acids and adipose tissue biology.

Kuda O, Rossmeisl M, Kopecky J.

Mol Aspects Med. 2018 Jan 9. pii: S0098-2997(17)30162-0. doi: 10.1016/j.mam.2018.01.004. [Epub ahead of print] Review.

PMID: 29329795

Abstract

This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL). The intrinsic metabolic features of WAT and their flexible regulations, reflecting the presence of "healthy adipocytes", provide beneficial local and systemic effects, including (i) protection against in situ endoplasmic reticulum stress and related inflammatory response during activation of adipocyte lipolysis; (ii) prevention of ectopic fat accumulation and dyslipidemia caused by increased hepatic VLDL synthesis, as well as prevention of lipotoxic damage of insulin signaling in extra-adipose tissues; and also (iii) increased synthesis of anti-inflammatory and insulin-sensitizing lipid mediators with pro-resolving properties, including the branched fatty acid esters of hydroxy fatty acids (FAHFAs), also depending on the activity of DNL in WAT. The "healthy adipocytes" phenotype can be induced in WAT of obese mice in response to various stimuli including dietary omega-3 PUFA, especially when combined with moderate calorie restriction, and possibly also with other life style (e.g. physical activity) or pharmacological (e.g. thiazolidinediones) interventions. While omega-3 PUFA could exert beneficial systemic effects by improving immunometabolism of WAT without a concomitant induction of BAT, it is currently not clear whether the metabolic effects of the combined intervention using omega-3 PUFA and calorie restriction or thiazolidinediones depend also on the activation of BAT function and/or the induction of brite/beige adipocytes in WAT. It remains to be established why omega-3 PUFA intervention in type 2 diabetic subjects does not improve insulin sensitivity and glucose homeostasis despite inducing various anti-inflammatory mediators in WAT, including the recently discovered docosahexaenoic esters of hydroxy linoleic acid, the lipokines from the FAHFAs family, as well as several endocannabinoid-related anti-inflammatory lipids. To answer the question whether and to which extent omega-3 PUFA supplementation could promote the formation of "healthy adipocytes" in WAT of human subjects, namely in the obese insulin-resistant patients, represents a challenging task that is of great importance for the treatment of some serious non-communicable diseases.

KEYWORDS:

Adipocytes; Bioavailability; Fish oil; Immunometabolism; Lipid mediators; de novo lipogenesis

 

Histomorphological Effects Of Hunger Stress On Ovaries.

Yousaf M, Siddiqi H, Waheed N.

J Ayub Med Coll Abbottabad. 2017 Oct-Dec;29(4):654-657.

PMID: 29330998

Abstract

BACKGROUND:

Incidence of stress is on the rise in our daily life involving various neurobiological, endocrinological and behavioral changes. Hunger stress has a potent influence on mental, physical, and reproductive health by affecting the hypothalamic-pituitary gonadal axis.

METHODS:

It was a laboratory based randomized control trial. Adult female mice (BALB-c strain) weighing 25-27 grams on first day of estrous cycle were taken in two groups (ten each). Group A was kept in normal environment of animal house for one month. Group B was given hunger stress by restricting the diet to about 50% per day for one month. Right ovaries of the animals were dissected out and observed for shape, color, and weight. Histological slides were prepared for the count of primary, secondary, and tertiary follicles.

RESULTS:

Statistically significant decrease in animal and ovary weight with significant fall in ovarian follicles was observed.

CONCLUSIONS:

Hunger stress affects the ovaries by reducing its weight and number of follicles.

KEYWORDS:

Hunger; Ovarian follicles; Ovary; Stress

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Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging.

Smiljanic K, Todorovic S, Mladenovic Djordjevic A, Vanmierlo T, Lütjohann D, Ivkovic S, Kanazir S.

Biogerontology. 2018 Jan 16. doi: 10.1007/s10522-018-9743-y. [Epub ahead of print]

PMID: 29340834

Abstract

Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats. We measured the impact of different DRs on the expression levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed the changes in the amounts of cholesterol, its metabolite, and precursors following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex while the increased levels were detected in the hippocampus. Glucose metabolism was more affected in the cortex, while cholesterol metabolism was more influenced in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with fewer changes compared to the cortex. We showed that LDF and IF differently affected the brain energy homeostasis during aging and that specific brain regions exhibited distinct vulnerabilities towards DRs. Consequently, special attention should be paid to the DR application among elderly as different phases of aging do not respond equally to altered nutritional regimes.

KEYWORDS:

AMPK; Aging; Brain; Cholesterol metabolism; Dietary restriction; Glucose transporters

 

Cardiovascular Risk Factors and Insulin Resistance after Two Hypocaloric Diets with Different Fat Distribution in Obese Subjects: Effect of the rs10767664 Gene Variant in Brain-Derived Neurotrophic Factor.

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

J Nutrigenet Nutrigenomics. 2018 Jan 17;10(5-6):163-171. doi: 10.1159/000485248. [Epub ahead of print]

PMID: 29339649

Abstract

BACKGROUND:

The role of brain-derived neurotrophic factor (BDNF) variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.

OBJECTIVE:

Our aim was to analyze the effects of the rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors, and serum adipokine levels after a high monounsaturated fatty acids (MUFAs) hypocaloric diet (diet M) versus a high polyunsaturated fatty acids (PUFAs) hypocaloric diet (diet P).

METHODS:

A Caucasian population of 361 obese patients was enrolled. Subjects who met the inclusion criteria were randomly allocated to one of two diets for a period of 3 months.

RESULTS:

Two hundred and sixteen subjects (59.8%) had the genotype AA (wild-type group), and 145 (40.2%) patients had the genotypes AT (122 patients, 33.8%) or TT (23 patients, 6.4%) (mutant-type group). After weight loss with diet P and diet M and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure, serum leptin levels, low-density lipoprotein cholesterol, and total cholesterol decreased in a significant way. Secondary to weight loss with diet M and only in the wild-type group, insulin levels (-2.1 ± 2.0 vs. -0.7 ± 2.9 IU/L, p < 0.05) and homeostatic model assessment of insulin resistance (-0.7 ± 0.9 vs. -0.3 ± 1.0 U, p < 0.05) decreased.

CONCLUSION:

Our data show that the rs10767664 variant of the BDNF gene modifies insulin resistance and insulin levels after weight loss with a hypocaloric diet enriched with MUFAs.

KEYWORDS:

Adipokines; Brain-derived neurotrophic factor; Hypocaloric diets; Insulin resistance; rs10767664

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Intermittent calorie restriction enhances epithelial-mesenchymal transition through the alteration of energy metabolism in a mouse tumor model.

Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, Kishi S, Miyagawa Y, Goto K, Kawahara I, Kuniyasu H.

Int J Oncol. 2018 Feb;52(2):413-423. doi: 10.3892/ijo.2017.4229. Epub 2017 Dec 18.

PMID: 29345287

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741368/

Abstract

The effect of intermittent calorie restriction (ICR) on cancer is controversial. In this study, we examined the effects of ICR and food content in syngeneic BALB/c mice injected with CT26 mouse colon cancer cells. Mice were subjected to 24-h fasting once a week for 4 weeks, and then provided with a control, high-calorie, or trans fatty acid-rich diet. While ICR resulted in increases in tumor weights, metastasis and in the number of cancer stem cells (CSCs) in the tumors or blood of mice fed the control and high-fat diets, it had no effect on body weight after 4 weeks. In particular, we detected increases in the numbers of CSCs in the tumor or blood on the day after starvation, when food overconsumption was detected. Conversely, continuous calorie restriction had no effect on tumor weight, metastasis, or the number of CSCs in tumors or blood. In the post-starvation period, energy metabolism in the tumor was altered from oxidative phosphorylation to glycolysis/lactate fermentation, with the acquisition of the epithelial-mesenchymal transition (EMT) phenotype. Hyperglycemia at the post-starvation period induced the expression of insulin-like growth factor-1, hypoxia-induced factor-1α and Nanog, as well as the phosphorylation of Stat3. Taken together, these findings suggest that ICR induces an increase in the number of CSCs and enhances EMT by promoting the Warburg/Crabtree effect following post-fasting food overconsumption.

 

Potential for diet to prevent and remediate cognitive deficits in neurological disorders.

Francis HM, Stevenson RJ.

Nutr Rev. 2018 Jan 15. doi: 10.1093/nutrit/nux073. [Epub ahead of print]

PMID: 29346658

Abstract

The pathophysiology of many neurological disorders involves oxidative stress, neuroinflammation, and mitochondrial dysfunction. There is now substantial evidence that diet can decrease these forms of pathophysiology, and an emerging body of literature relatedly suggests that diet can also prevent or even remediate the cognitive deficits observed in neurological disorders that exhibit such pathology (eg, Alzheimer's disease, multiple sclerosis, age-related cognitive decline, epilepsy). The current review summarizes the emerging evidence in relation to whole diets prominent in the scientific literature-ketogenic, caloric restriction, high polyphenol, and Mediterranean diets-and provides a discussion of the possible underlying neurophysiological mechanisms.

KEYWORDS:

Mediterranean; caloric restriction; cognition; fasting; ketogenic; polyphenol

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