The practice of calorie restriction has been shown to extend both healthy and overall life span in near every species tested to date - though of course the human life span data is still too sparse to do more than make educated guesses. Calorie restriction also provides considerable short term benefits to measures of heath, larger than anything that medical science can presently provide for basically healthy individuals, and the short term human data matches that obtained from other mammals. Eating less while maintaining optimal levels of micronutrients is a healthy practice, with a weight of evidence backing that claim, even if there is considerable uncertainty over the degree to which it will lengthen human life. It certainly doesn't produce the same 40% extension of life observed in mice, as that outcome would have been noted centuries past. As a general rule the life spans of short-lived species are far more plastic in response to circumstances than those of long-lived species. The consensus in the research community is that calorie restriction, while being very good for your health, and significantly reducing incidence of age-related disease, probably doesn't add more than five years of life at the outside.
Almost every measure of aging is slowed and almost every aspect of cellular metabolism is altered in calorie restricted individuals. Nutrient sensing mechanisms touch on all of the low-level, important cellular behaviors, such as replication and maintenance processes, and this has made it very difficult to understand how exactly the calorie restriction response works. Understanding calorie restriction cannot easily be separated from the vast undertaking of building a complete understanding of cellular biochemistry and the way in which it changes over the course of aging - and why. Some major areas of interest in cellular biology have been blocked out by the aging research community, such as insulin signaling, sirtuins, mTOR, and so forth. Over the past twenty years a great deal of time and funding has gone towards mapping more of these mechanisms, in search of ways to reproduce calorie restriction without the dieting, but for all that effort there are few signs that an end is in sight. Human biochemistry is enormously complex.
The paper here is an example of one of the many ways in which calorie restriction slows the progression of aging. The researchers provide evidence to show that the earliest stages of cancer advance more slowly and are in general suppressed in calorie restricted animals. Cancer is a manifestation of aging in the sense that it is a numbers game: firstly, the more damage to DNA that an individual suffers, the more likely that a cancerous cell arises. Secondly the mechanisms responsible for assassinating cancerous cells falter with age due to their own burden of damage and dysfunction. Lastly the inflamed environment of old tissues makes it easier for cancers to thrive once they get underway. Calorie restriction has a positive impact on all of these points, and hence calorie restricted individuals have a lower incidence of cancer. Understanding exactly why this is the case at a deep enough level to produce therapies that replicate its effects is whole different story, of course, and something than may not happen for decades yet.
Neoplastic disease is inextricably associated with aging. Five out of six cancer-related deaths occur in patients aged 60 years and older. However, the intimate nature of this association is yet to be fully clarified. An important concept emerging from the literature is that aging and cancer do not merely represent two chronologically parallel processes, but they share relevant pathogenetic mechanisms. Along these lines, in a recent study we have provided evidence to indicate that aging promotes the growth of pre-neoplastic cells through alterations imposed on the tissue microenvironment, i.e. by generating an age-associated, neoplastic-prone tissue landscape. Similarly, it has been reported that aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors; it was proposed that cell competition may in fact drive the emergence of oncogenically altered cells in a background of age-induced decline in tissue fitness, in a process that has been referred to as "adaptive oncogenesis".
The notion that age-associated tissue changes may play a direct role in the origin of neoplasia has far-reaching implications. It suggests that strategies aimed at modulating the rate of aging may have a direct impact on early and/or late steps of neoplastic disease, i.e. the quest for a longer lifespan may coincide, at least in part, with the goal to defer the occurrence of cancer.
A most effective and consistent means to delay aging is by reducing caloric intake compared to ad libitum (AL) feeding. Caloric restriction (CR) is the most studied and reproducible non-genetic intervention known to extend lifespan in organisms ranging from unicellular yeast to mammals, including non-human primates, although the latter observation is disputed. On the other hand, it is also well documented that CR exerts a beneficial effect on the incidence of chronic diseases related to old age, including cancer, consistent with the notion that changes occurring during the aging process may bear direct relevance to the pathogenesis of neoplasia. However, the precise mechanisms responsible for the CR-induced delay on carcinogenic process are yet to be identified.
Based on the above, in the present studies we tested the hypothesis that the modulatory effect of CR on age-associated neoplastic disease might be related, at least in part, to a CR-induced delay in the emergence of age-related tissue alterations promoting the growth of pre-neoplastic cells. Using a well characterized cell transplantation system in the rat, we report that when pre-neoplastic hepatocytes were infused in aged animals exposed to either AL or CR diet, their growth was significantly reduced in the latter group. Analysis of donor-derived cell clusters performed at 10 weeks post-transplant revealed a significant shift towards smaller class sizes in the group receiving CR diet. Clusters comprising more than 50 cells, including large hepatic nodules, were thrice more frequent in AL vs. CR animals. Incidence of spontaneous endogenous nodules was also decreased by CR. These results are interpreted to indicate that CR delays the emergence of age-associated neoplastic disease through effects exerted, at least in part, on the tissue microenvironment.
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