How Eating Less Might Make You Live Longer

A calorie-restricted diet provides all the nutrients necessary for a healthy life but minimizes the energy (calories) supplied in the diet. This type of diet increases the life span of mice and delays the onset of age-related chronic diseases such as cancers, heart disease, and stroke in rodents. There are also hints that people who eat a calorie-restricted diet might live longer than those who overeat. In addition, calorie-restricted diets beneficially affect several biomarkers of aging, including decreased insulin sensitivity (a precursor to diabetes). But how might caloric restriction slow aging? A major factor in the age-related decline of bodily functions is the accumulation of "oxidative damage" in the body's proteins, fats, and DNA. Oxidants--in particular, chemicals called "free radicals"--are produced when food is converted to energy by cellular structures called mitochondria. One theory for h ow caloric restriction slows aging is that it lowers free-radical production by inducing the formation of efficient mitochondria.

Civitarese and colleagues enrolled 36 healthy overweight but non-obese young people into their study. A third of them received 100% of their energy requirements in their diet; the caloric restriction (CR) group had their calorie intake reduced by 25%; and the caloric restriction plus exercise (CREX) group had their calorie intake reduced by 12.5% and their energy expenditure increased by 12.5%. The researchers found that a 25% caloric deficit for 6 months, achieved by diet alone or by diet plus exercise, decreased 24hr whole body energy expenditure (i.e. overall calories burned), which suggests improved mitochondrial function. Their analysis of genes involved in mitochondria formation indicated that CR and CREX both increased the number of mitochondria in muscle. Both interventions also reduced the amount of DNA damage--a marker of oxidative stress--in the participants' muscles.

The researchers also examined gene expression in the study participants. In yeast, worms, and flies the activation of the Sir2 gene increases life span and regulates cellular metabolism. An important question is whether caloric restriction can regulate SIRT1 (the mammalian equivalent of Sir2) in humans. Civitarese and colleagues found that indeed fewer calories can improve whole body metabolism in conjunction with an increase in SIRT1 gene expression in skeletal muscle. These results raise the possibility that SIRT1 may contribute to more efficient metabolism, less oxidative stress, and increase longevity in humans as it does in lower organism.

The results suggest that even short-term caloric restriction can produce beneficial physiological changes leading to improved health. Whether caloric restriction and the associated health benefits can be sustained over longer term remains to be established in humans.

Citation: Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, et al. (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4(3): e76. (http://dx.doi.org/10.1371/journal.pmed.0040076)