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Dean Pomerleau posted a topic in CR Science & TheoryAll, It's been argued by respected aging researchers like Luigi Fontana that CR is likely to extend human lifespan through its effects on the somatotropic axis  - the signalling pathway involving growth hormone, insulin and IGF-1. In fact, Luigi argues that the monkeys in the NIA CR longevity trial may not have benefited because they may not have been restricted enough to show the biomarkers of CR-induced extended longevity, which especially includes low IGF-1, as has been observed in CRed rodents, and like he has observed in long-term human CR practitioners from the CR Society. This new review article  begs to differ. It uses two lines of reasoning to argue that modulation of the IGF-1 pathway via CR, genetic manipulation or drugs, won't extend human lifespan. The first argument is an evolutionary one that has been made before (e.g. by Aubrey) - that humans use different strategies unavailable to rodents and other lower organisms for dealing with food shortage - i.e. migration, and so humans wouldn't have had the evolutionary pressure to maintain the genetic machinery to hunker down and boost longevity when faced with famine. The second line of argument looks at data from a variety of non-rodent animal and human studies of the association between the IGF-1 pathway and longevity. He suggests the fact that CR didn't work in the NIA monkeys suggests it won't work in humans, although as mentioned above it's unclear how restricted the NIA CR monkeys were, or whether the CR monkeys' IGF-1 pathway was downregulated (somewhere on these forums Michael points to evidence that it was...). The author also points to data from dwarf humans with congenitally low IGF-1 who he says don't live longer. He looks at studies of gene polymorphisms involving expression of IGF-1 and says people with genetically-low IGF-1 levels don't live longer. He says studies of IGF-1 levels of centenarians and their offspring have been equivocal at best. He criticizes data showing shorter people live longer, and even questions the longevity of traditional Okinawans. He's a real skeptic, concluding: The main conclusion of this article is that modulation of the somatotropic axis does not explain longevity variations of ad libitum-fed animals but is a tool to face food shortage, leading to increased longevity in some species only. One can hope that a better knowledge of this axis could help to fight various pathologies, such as obesity not linked to an excessive food intake. However, one should give up the idea that it could help to modulate the ageing process and increase longevity of people not suffering from metabolic disorders. This post by Brett Black argues that low IGF-1 is likely to be detrimental, while the two that follow it in that thread (by me and Michael), suggest the opposite - that lower IGF-1 is indeed associated with improved longevity in humans, contra what the current paper  suggests. It seems hard to say who's right on this, given the evidence available to us about the effect of IGF-1 on human longevity, and (unfortunately) the evidence likely to be available to us during our lifetimes... --Dean ----------  Biogerontology. 2016 Apr;17(2):421-9. doi: 10.1007/s10522-015-9632-6. Epub 2015 Dec 28. The somatotropic axis may not modulate ageing and longevity in humans. Le Bourg É(1). Full text: http://sci-hub.io/10.1007/s10522-015-9632-6 Studies in nematodes and mice have shown that the somatotropic axis can modulate their longevity and it has been argued that it could also modulate human longevity. Thus, like nematodes and mice, human beings should live longer when facing starvation and genetic variation of the somatotropic axis should be linked to longevity. This article argues that, because the life-history strategies of humans are very different from those of mice, these hypotheses are not warranted. PMID: 26712318 --------  Aging (Albany NY). 2013 Jul;5(7):507-14. Will calorie restriction work in humans? Cava E(1), Fontana L. Author information: (1)Division of Geriatrics and Nutritional Science and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63130, USA. Calorie Restriction (CR) without malnutrition slows aging and increases average and maximal lifespan in simple model organisms and rodents. In rhesus monkeys long-term CR reduces the incidence of type 2 diabetes, cardiovascular disease and cancer, and protects against age-associated sarcopenia and neurodegeneration. However, so far CR significantly increased average lifespan only in the Wisconsin, but not in the NIA monkey study. Differences in diet composition and study design between the 2 on-going trials may explain the discrepancies in survival and disease. Nevertheless, many of the metabolic and hormonal adaptations that are typical of the long-lived CR rodents did not occur in either the NIA or WNPRC CR monkeys. Whether or not CR will extend lifespan in humans is not yet known, but accumulating data indicate that moderate CR with adequate nutrition has a powerful protective effect against obesity, type 2 diabetes, inflammation, hypertension, cardiovascular disease and reduces metabolic risk factors associated with cancer. Moreover, CR in human beings improves markers of cardiovascular aging, and rejuvenates the skeletal muscle transcriptional profile. More studies are needed to understand the interactions between CR, diet composition, exercise, and other environmental and psychological factors on metabolic and molecular pathways that regulate health and longevity. PMCID: PMC3765579 PMID: 23924667
On the thread about cranberries, Rodney got us talking about prunes, and how they may be good for maintaining bone health via increased IGF-1, which is a double-edged sword. This is pretty well-known among knowledgeable CR practitioners, but I thought it worth highlighting, particularly since I came across this interesting discussion & video on the potential tradeoff between "performance" and longevity with respect to IGF-1. It discusses (and gives citations) for many of the benefits of IGF-1, including muscle repair/preservation as well as long-term cognitive health. Interestingly, it doesn't mention helping maintain bone health as another benefit of the anabolic effects of IGF-1. But on the downside, it talks about increased cancer risk and the widely-observed reduced longevity (in humans and animals) associated with higher levels of IGF-1. Here is the summary paragraph: There you have it. It’s a trade-off when it comes to growth hormone and IGF-1. More of it enhances muscle and neuronal growth while simultaneously preventing atrophy. Less of it will increase the expression of stress resistance genes and extend your lifespan. Which do you prefer, having better muscle and cognitive performance or living longer? Overall, it seems like a good primer for anyone who wants to learn about the pros and cons of the reduced IGF-1 often associated with practicing CR. --Dean