CR in Nonhuman Primates: A Muddle for Monkeys, Men, and Mimetics
(for the advanced reader)
Calorie restriction (CR) is the most well-characterized and arguably the most robust intervention into the degenerative aging process in experimental animals. Biomedical gerontologists have therefore proposed "CR mimetics" — pharmacological modulators of the signaling pathways underlying the age-retarding effects of CR — as a route to the development of interventions against the diseases and disabilities of aging. The viability of this strategy necessarily depends upon the human translatability of CR. Lifespan studies in human CR being impracticable, studies in longevous nonhuman primates were initiated at the Wisconsin National Primate Research Center (WNPRC) and at the National Institute on Aging (NIA) to give strong surrogate evidence on the issue. Disconcertingly, the two studies have come to opposing outcomes, with CR extending life relative to controls at WNPRC and not doing so at NIA. This article explores several possible interpretations of the discrepancy, focusing on two with the greatest explanatory power. Both interpretations begin from the premise that the WNPRC control animals were overfed, and that the "CR" animals in that study — as well as the control animals at NIA — were healthier by comparison for the trivial reason that they were not suffering the metabolic consequences of obesity. In the "diminishing returns" hypothesis, there was no increase in lifespan in NIA CR animals relative to nonobese controls because there is nothing to be gained from reducing food intake beyond what is needed to remain reasonably lean; thus, CR is not translatable to human or nonhuman primates, and CR mimetics cannot even in principle be created. In the "dose-response" hypothesis, the NIA's null result is interpreted as resulting from an inadequate and progressively declining degree of CR relative to the healthy baseline of the ad libitum group; this interpretation is supported with data on food motivation, body composition, and the metabolic responses to CR, and with reference to the effects of CR on the latter parameters in laboratory rodents and in humans. While the "dose-response" hypothesis holds out hope for the human translatability of CR (and thus, the theoretical possibility of true CR mimetics), there remain inherent and likely insurmountable barriers to the development of CR mimetics as effective interventions for human use, and thus researchers are urged to redirect their efforts toward rejuvenation biotechnology for the rapid and maximally effective development of new therapies to prevent and cure the diseases and disabilities of aging.http://www.sens.org/research/research-blog/cr-nonhuman-primates-muddle-monkeys-men-and-mimetics
Here, a very understandable and concise review on growth hormones and aging:
A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth.
Gerontology. 2012;58(4):337-43. doi: 10.1159/000335166. Epub 2012 Jan 18.
Healthy aging: is smaller better? - a mini-review. Bartke A.