Caloric restriction improves health and survival of rhesus monkeys

Mattison, Julie A.; Colman, Ricki J.; Beasley, T. Mark; Allison, David B.; Kemnitz, Joseph W.; Roth, George S.; Ingram, Donald K.; Weindruch, Richard; Cabo, Rafael de; Anderson, Rozalyn M.

doi:10.1038/ncomms14063

Cited by 706 publications

(521 citation statements)

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“…In contrast, increasing autophagy in worms (Hansen et al 2008) and flies (Simonsen et al 2008) extends lifespan. Interestingly, calorie restriction without malnutrition increases autophagy in rats (Kume et al 2010) and extends life span (Weindruch and Walford 1982) and monkeys (Mattison et al 2017). While the exact mechanism by which calorie restriction enhances autophagy is unclear, it is thought to involve AMPK or Sirtuin 1 stimulation or insulin-like growth factor inhibition (Johnson et al 2013).…”

Section: Autophagy and Agingmentioning

confidence: 99%

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

et al. 2017

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While cognitive decline is observed in the normal aging monkey, neurons are not lost with age. Instead, frontal white matter is lost as myelin degenerates and both correlate with age-related cognitive decline. As age-related myelin damage increases, there should be an increase in clearance of damaged myelin by microglial phagocytosis. In this study, brains of behaviorally tested rhesus monkeys were assessed using unbiased stereology to quantify the density of activated microglia (LN3 antibody positive) and phagocytic microglia (galectin-3 (Gal-3) antibody positive) in three white matter regions: the corpus callosum, cingulum bundle (CGB), and frontal white matter (FWM). LN3 cell density was significantly increased in the CGB, whereas Gal-3 cell density was significantly increased in all regions. Increases in Gal-3 cell density in the FWM were associated with cognitive impairment. In the FWM of old animals, Gal-3-positive microglia were classified by morphological subtype as ramified, hypertrophic, or amoeboid. The densities of hypertrophic and amoeboid microglia significantly correlated with cognitive impairment. Finally, microglia were double-labeled with LN3 and Gal-3 showing that 91% of Gal-3 cells were also LN3 positive, thus expressing an Bactivated^phenotype. Furthermore, 15% of all double-labeled cells formed phagocytic cups. Overall, these results suggest that microglia become activated in white matter with age where the majority express a phagocytic phenotype. We hypothesize that age-related phagocytic activation of microglia is a response to accumulating myelin pathology. The association of Gal-3 in the FWM with cognitive impairment may reflect regional differences in damage or dysfunction of normal clearance mechanisms.

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Section: Autophagy and Agingmentioning

confidence: 99%

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

et al. 2017

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“…Similarly, secondary aging or incidences of agerelated diseases such as diabetes, cardiovascular diseases, and some forms of cancers are delayed by CR, probably through alterations in neuroendocrine activities (4,5). Research in nonhuman primates has suggested that the mortality rate is lower in CR animals than in control animals (6)(7)(8)(9)(10)(11)(12). Naturally occurring episodes of CR exist in humans (4,(13)(14)(15)(16)(17)(18)(19)(20)(21) and provide important information on changes in biomarkers of aging.…”

Section: Introductionmentioning

confidence: 99%

Persistence of weight loss and acquired behaviors 2 y after stopping a 2-y calorie restriction intervention

Marlatt¹,

Redman²,

Burton³

et al. 2017

The American Journal of Clinical Nutrition

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Background: Calorie restriction (CR) influences aging processes and extends average and maximal life spans. The CALERIE 2 (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy Phase 2) study was the first randomized clinical trial to examine the metabolic and psychological effects of CR in nonobese humans. Objective: We conducted a 2-y follow-up study of adults who underwent 2 y of CR or ad libitum (control) consumption and determined whether weight loss and acquired behaviors persisted after the study ended when participants determined their own lifestyle behaviors. Design: In this prospective, longitudinal study, we assessed differences in weight, body composition, psychological function, and energy expenditure in 39 nonobese [body mass index (in kg/m 2 ): 22-28] men and women (25% CR: n = 24; control: n = 15) 12 and 24 mo after they completed the CALERIE 2 study at Pennington Biomedical. Results: Of 39 participants who were in the follow-up study, 29 subjects (CR: n = 18; control: n = 11) completed all visits at followup months 12 and 24. After the CR intervention, a mean 6 SEM weight loss of 9.0 6 0.6 kg was observed in the CR group, in which only 54% of the weight was regained 2 y later. Despite such a regain, weight, the percentage of body fat, and fat mass remained significantly reduced from baseline throughout follow-up and remained significantly less than in the control group (P , 0.05). At follow-up, the CR group retained higher degrees of dietary restraint and avoidance of certain foods. Conclusion: After a 2-y intensive CR intervention, w50% of CR-induced weight loss was maintained 2 y later, which was probably the result of lasting effects on acquired behaviors and dietary restraint. This trial was registered at clinicaltrials.gov as NCT00943215.Am J Clin Nutr 2017;105:928-35.

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“…This contradiction is speculated to result from differences between the two facilities in the breeding environment, such as diet composition, timing of feeding, and the genetic background of the experimental animals 2) . In a reanalysis of recent studies, CR was reported to extend the life expectancies of rhesus monkeys in NIA studies 3) . These results suggest that CR has a lifespan-prolonging effect in primates and may improve the quality of life in humans by suppressing the development of age-related diseases.…”

Section: Cr Biomarkersmentioning

confidence: 99%

“…However, changes to biomarkers found in humans with potentially long lifespans, such as people with low body temperatures or low blood insulin levels, are similar to those found in calorie-restricted animals. In addition, reports from two independent research groups on rhesus macaques demonstrate that CR exerts anti-aging and lifespan extension effects on primates [1][2][3] . Despite its potential lifespan-extending effects, CR is difficult to implement for a prolonged period in humans because it also exerts severe physiological and psychological side effects.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of action of compounds that mimic beneficial effects of calorie restriction such as lifespan extension: Is taurine a promising candidate?

Nishizono

Wang

Watanabe

et al. 2017

JPFSM

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More than 80 years ago, McCay and colleagues first reported that limiting the amount of food provided to experimental animals (i.e. calorie restriction or CR) prolongs their lifespan and suppresses the onset and progression of various age-related diseases. Today, CR remains the most reliable method of delaying aging in experimental animals, and research into its underlying molecular mechanisms is ongoing. CR has been reported to have anti-aging and life-extension effects on primates, with progress being made toward applications for humans. Studies on mechanisms underlying the onset and prevention of lifestyle-related diseases such as diabetes have elucidated the cellular signaling pathways that regulate energy metabolism, and commonalities have been discovered between the targets of existing diabetes drugs and the signaling pathways affected by CR. This finding has led to research into the discovery of drugs that have the anti-aging effects of CR in the absence of food intake limitations, namely CR mimetics (CRM). Several drugs have been reported to extend the lifespan of experimental organisms, which may thus have the potential to also extend human lifespan. In this article, we outline and compare those drugs that have been reported to date and discuss the possibility of taurine as a CRM, which is a topic of our ongoing research.

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Caloric restriction improves health and survival of rhesus monkeys

Cited by 706 publications

References 50 publications

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

Persistence of weight loss and acquired behaviors 2 y after stopping a 2-y calorie restriction intervention

Mechanisms of action of compounds that mimic beneficial effects of calorie restriction such as lifespan extension: Is taurine a promising candidate?

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