Rodents fed 25-60% less than free-feeding controls can live up to 50% longer. This is a cross-species effect, holding true for yeast, rotifers, spiders, worms, mice, fish, and rats, and maybe non-human primates (although the longer the animal lives, the more expensive this effect is to establish). It is known to delay a number of diseases in animal models, but how? Koubava et al (2003) set out to explain the mechanism. They analyze three main models.
One is the theory that oxidative damage caused by reactive oxygen species leads to cellular degradation. If caloric restriction (CR) reduces metabolism, oxidative damage should be reduced as a simple consequence. Oxidative damage has shown to be lower in CR animals, but metabolism is not slower by most measures (although measuring this is non-trivial).
The second theory is that CR speeds up protein turnover, which delays aging because aberrant proteins and a reduction of protein turnover are tell-tale signs of aging. Perhaps it does this because when the body runs out of fat it triggers the degradation and therefore the turnover of proteins. There is some evidence for this, but the increase in protein turnover is not uniform throughout the body: some regions show it and some regions do not.
Finally, it is possible that CR leads to a decrease in protein modification by advanced glycation end products that are associated with age-related diseases. This has been demonstrated empirically, but it does not explain all of the beneficial effects of CR and therefore is unlikely to be the primary mechanism.
The authors review the evidence and present their own combinatorial model that relies on hormone regulation. This is a controversial yet potentially enlightening topic for neuroscientists.
Koubova J, Guarente L. 2003 How does caloric restriction work. Genes and Development 17:313-321. doi: