Human Longevity Not Due to Always-On Calorie Restriction Responses

Humans are long-lived in comparison to other primates, as well as in comparison to other mammal species of a similar size. Given that we don't experience the same degree of enhanced longevity in response to calorie restriction as occurs in shorter-lived species, some researchers have hypothesized that in the course of evolving greater longevity - perhaps due to the grandmother effect - some of the changes that occur in metabolism under calorie restriction in those shorter-lived species become permanently turned on in humans.

If this is in fact true, then we would expect only limited benefits to result from the development of calorie restriction mimetic drugs: anything that looked promising in mice and even primates would not work as well in people. We might think, however, based on the degree to which calorie restriction is demonstrated to improve health in humans, that this hypothesis of always-on calorie restriction responses is not the case. The research here adds some supporting evidence to this view, but leaves standing the question of how calorie restriction can produce similar sweeping changes in health and metabolism in both humans and mice, and yet only the mice have a large extension of life span:

Caloric restriction (CR) and chemical agents, such as resveratrol and rapamycin that partially mimic the CR effect, can delay morbidity and mortality across a broad range of species. In humans, however, the effects of CR or other life-extending agents have not yet been investigated systematically. Human maximal lifespan is already substantially greater compared to that of closely related primate species. It is therefore possible that humans have acquired genetic mutations that mimic the CR effect.

Here, we tested this notion by comparing transcriptome differences between humans and other primates, with the transcriptome changes observed in mice subjected to CR. We show that the human transcriptome state, relative to other primate transcriptomes, does not match that of the CR mice or mice treated with resveratrol, but resembles the transcriptome state of ad libitum fed mice. At the same time, the transcriptome changes induced by CR in mice are enriched among genes showing age-related changes in primates, concentrated in specific expression patterns, and can be linked with specific functional pathways, including insulin signalling, cancer, and the immune response.

These findings indicate that the evolution of human longevity was likely independent of CR-induced lifespan extension mechanisms. Consequently, application of CR or CR-mimicking agents may yet offer a promising direction for the extension of healthy human lifespan.



Hopefully, this methodology will allow pharma-/nutra-ceutical firms to rapidly screen drugs, nutrients, herbs ,..., for anti-aging effects and to identify real CR-mimetics.

Posted by: Lou Pagnucco at January 7th, 2014 12:23 PM

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