X-Message-Number: 13051
Date: Mon, 03 Jan 2000 17:49:30 -0500
From: Jan Coetzee <>
Subject: Revisiting caloric restriction

Revisiting the role of fat mass in the life extension induced
                  by caloric restriction.

                  Barzilai N, Gupta G

                  Department of Medicine, Albert Einstein College of
Medicine, Montefiore
                  Medical Center, Bronx, New York, USA.

                  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 a severalfold decrease in fat mass (FM), the role
of fat on life extension
                  was considered to be minimal. Two main reasons
accounted for this
                  belief. First, although increased FM is associated
with changes in
                  substrate oxidation and in glucose homeostasis, in
part through the effects
                  of free fatty acids (FFA) and glycerol, several
studies have suggested that
                  longevity is determined independent of FM. Second, CR
has systemic
                  effects on a range of functions including
neurological, endocrine,
                  reproductive, immunological and antineoplastic, none
of which have been
                  historically linked to fat. In the last few years, an
explosion of evidence
                  has demonstrated that fat tissue is a very active
endocrine gland which
                  secretes a variety of peptides (such as leptin and
plasminogen activating
                  inhibitor-1), cytokines (such as tumor necrosis
factor), and complement
                  factors (such as D, C3, and B). This is in addition to
the presence of
                  substrates, such as glycerol and FFA, which are stored
and released by fat
                  cells and are known to have a major role in hepatic
and peripheral
                  glucose metabolism. We propose that 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. In fact,
                  all of the benefits of CR on the neuroendocrine system
and those related to
                  the improvement in glucose homeostasis can be
attributed to decrease in
                  adipose cells and their products. Other evidence from
                  data in human obesity supports the role of fat mass
and its body
                  distribution as a risk factor for morbidity and
mortality in humans due to
                  impaired glucose metabolism (similar to rodents), for
cancer (similar to
                  rodents), and for the development of atherosclerotic
vascular disease (in
                  humans). If all or most of the life-extending benefits
of CR can be
                  attributed to decreased fat stores, the expression of
specific candidate
                  proteins may be explored and manipulated in the search
for the most
                  powerful adipose-dependent signals that modulate life

1 : J Gerontol A Biol Sci Med Sci 1999
               Mar;54(3):B89-96; discussion B97-8

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