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Supplement

The Role of Fat Depletion in the Biological Benefits of Caloric Restriction^{1 ,2}

Department of Medicine, Divisions of Geriatrics, Endocrinology and the Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY 10461

³To whom correspondence should be addressed. E-mail: barzilai{at}aecom.yu.edu

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 amount of fat has been directly implicated in the metabolic consequences. Since it became apparent that fat is a massive endocrine tissue, some of its roles 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 peptides, cytokines, complement factors and substrates that are produced in fat. Most of the benefits of CR on the neuroendocrine system and those related to the improvement in glucose homeostasis can be attributed to a decrease in adipose cells and their products. If all or most of the life-extending benefits of CR can be attributed to decreased fat stores, the expression of specific candidate substrates and proteins may be explored and manipulated in searching for the most powerful adipose-dependent signals that modulate life expectancy.

KEY WORDS: • caloric restriction • fat mass • visceral fat • obesity • insulin sensitivity • fat-derived peptides

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