J. Koochmeshgi

Dietary restriction experiments provide a model for exploring the phenomenon of aging. Plasma levels of several biomolecules are known to change as a result of dietary restriction and these biomolecules have been considered for their possible role in aging. We have proposed a hypothesis for interpreting extension of life by dietary restriction. It posits that normal food intake is geared toward optimizing the internal milieu for reproduction, even though some components of this milieu may be detrimental to health in the long term. In dietary restricted state, this particular milieu, with its detrimental effects on health, does not materialize and life extension occurs as a by-product. This hypothesis can provide a conceptual framework for exploring biomolecular changes seen in dietary restriction and their relevance to aging. Leptin is a case in point: Leptin, a biomolecule secreted from adipose tissue, has receptors in hypothalamus and is involved in suppressing appetite and activating hypothalamic-pituitary-gonadal axis. A picture has emerged for the role of leptin in the centrally integrated system monitoring body fat reserve, regulating appetite, and signalling reproductive competence. Plasma levels of leptin decrease in dietary restriction and this has led to considerations about its possible role in aging. We think that decrease in leptin level observed in dietary restricted animals can be explored in the light of leptins role in this complex and integrated signalling system, the reproductive switch. Does this decrease simply reflect the insufficiency of bodys fat reserve for reproduction, and is the observed extension in life attributable to the fact that reproductive competence is not signalled and downstream events with their possible detrimental effects on health do not occur? Or does leptin have some specific effect on the process of aging by itself? And if so, does this effect appear only in the context of integrated changes associated with reproductive switch or independent of them? Experiments aimed at uncoupling components of reproductive switch and downstream events should help in resolving these issues. These questions find parallels in the study of the role of insulin-like growth factor 1 in transgenic models of aging.

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Dietary Restriction