Recent Calorie Restriction Research

Posted: April 28, 2013 at 2:57 am

Human calorie restriction studies continue onward at the normal sedate pace of all human research, as noted in a recent post on the CALERIE program. It remains the case that the vast majority of work on calorie restriction and its beneficial effects involves mice, flies, worms, and other laboratory animals. Most such species exhibit increased longevity and improved measures of long term health when on a calorie restricted diet, provided that they still receive suitable levels of nutrition. That this is so universal is one of the reasons to suggest calorie restriction with optimal nutrition as a lifestyle choice in humans.

Other reasons include the results from human studies to date; if there was a pill you could take that provided half the benefits that calorie restriction has been shown to produce in humans, then everyone would be falling over themselves to take it. It's somewhat harder to convince people to eat less in this day and age, however, no matter how beneficial the results might be. The paper quoted below is illustrative of results from human studies, in that the measures taken tend to line up with what is seen in short-lived animals like mice and rats:

Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile

Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR-induced dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis and inflammation.

If you wander over to Extreme Longevity you can find a PDF copy of the full paper.

The fact that more easily gathered measures of metabolism like those noted above are similar for rat and human calorie restriction makes CR look like a good option - where these measures match up, the hope is that the long term rewards do so as well. Studies in rats can achieve what studies in humans cannot, which is to follow large numbers of rats for their entire lives and catalog the impressive long term health benefits, as well as the characteristic increase in life expectancy, that accompanies CR in rodent species. This is one of many examples, in which the researchers focus as much on exercise as CR:

Effects of dietary restriction and exercise on the age-related pathology of the rat

The most efficacious and commonly used intervention used to retard the aging processes is dietary restriction (DR). It increases mean and maximum life spans, delays the appearance, frequency, and severity of many age-related diseases, and more importantly, attenuates much of the physiological decline associated with age. Although the subject of intense research, the mechanism by which DR alters the aging processes is still unknown.

Physical exercise is another effective intervention shown to affect aging phenomena, especially when applied in combination with DR. Mild exercise in concert with DR is beneficial, but vigorous exercise coupled with DR could be deleterious. With regard to pathology, exercise generally exerts a salutary influence on age-related diseases, both neoplastic and non-neoplastic, and this effect may contribute to the increase in median life span seen with exercised rats.

Exercise coupled with 40% DR was found to suppress the incidence of fatal neoplastic disease compared to the sedentary DR group. Exercise with mild DR suppressed the incidence of multiple fatal disease and chronic nephropathy, and also delayed the occurrence of many age-related lesions compared to the ad libitum (AL) control group. However, these effects may have little bearing on the aging process per se, as maximum life span is only minimally affected. Although not as intensively studied as DR, results from studies that utilize exercise as a research probe, either alone or in combination with DR, have helped to assess the validity of proposed mechanisms for DR and aging itself.

Neither the retardation of growth rate nor the increase in physical activity, observed with either exercise or DR, appear to contribute to the anti-aging action of DR. Moreover, results from lifelong exercise studies indicate that the effects of DR do not depend upon changes in energy availability or metabolic rate. The mechanisms involving effects on adiposity or immune function are also inadequate explanations for the action of DR on aging. Of the proposed mechanisms, only one, as postulated by the Oxidative Stress Hypothesis of Aging, tenably accounts for the known effects of DR and exercise on aging.

Source:
http://www.fightaging.org/archives/2013/04/recent-calorie-restriction-research.php

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