BACKGROUND: Calorie Restriction (CR) research has expanded rapidly over the past
few decades and CR remains the most highly reproducible, environmental
intervention to improve health and extend lifespan in animal studies. Although
many model organisms have consistently demonstrated positive responses to CR, it
remains to be shown whether CR will extend lifespan in humans. Additionally, the
current environment of excess caloric consumption and high incidence of
overweight/obesity illustrate the improbable nature of the long-term adoption of
a CR lifestyle by a significant proportion of the human population. Thus, the
search for substances that can reproduce the beneficial physiologic responses of
CR without a requisite calorie intake reduction, termed CR mimetics (CRMs), has
gained momentum. MATERIAL AND METHODS: Recent articles describing health and
lifespan results of CR in nonhuman primates and short-term human studies are
discussed. Additional consideration is given to the rapidly expanding search for
CRMs. RESULTS: The first results from a long-term, randomized, controlled CR
study in nonhuman primates showing statistically significant benefits on

BACKGROUND: Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. METHODS AND FINDINGS: The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05).

For lean mice – and possibly for lean humans, the authors of a new study predict – the anti-aging strategy known as caloric restriction may be a pointless, frustrating and even dangerous exercise.

"Today there are a lot of very healthy people who look like skeletons because they bought into this," said Raj Sohal, professor at the University of Southern California's School of Pharmacy.

He and Michael Forster, of the University of North Texas Health Science Center, compared the life span and caloric intake of two genetically engineered strains of mice.

The "fat" strain, known as C57BL/6, roughly doubles in weight over its adult life. That strain benefited from caloric restriction, Sohal said.

The "lean" strain, DBA/2, does not become obese. Caloric restriction did not extend the life of these mice, confirming previous work by Forster and Sohal.