The role of fat depletion in the biological benefits of caloric restriction

One of the most robust observations in the biology of aging is that caloric restriction (CR) extends life in a variety of species. Although CR results in substantial decrease in fat mass, the role of fat in life extension was considered minimal. Indeed, in the fields of obesity and diabetes, the amo unt of fat has been directly implicated in the metabolic consequences. Sinc e it became apparent that fat is a massive endocrine tissue, some of its ro les have been recently revised. Many of the systemic effects of CR can now be explained by the chronic effects related to decreased plasma levels of p eptides, cytokines, complement factors and substrates that are produced in fat. Most of the benefits of CR on the neuroendocrine system and those rela ted to the improvement in glucose homeostasis can be attributed to a decrea se in adipose cells and their products. If all or most of the life-extendin g benefits of CR can be attributed to decreased fat stores, the expression of specific candidate substrates and proteins may be explored and manipulat ed in searching for the most powerful adipose-dependent signals that modula te life expectancy.