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Effect of Aging and Anti-Aging Caloric Restriction on the Endocrine Regulation of Rat Liver Autophagy

Centro di Ricerca Biologia e Patologia dell'Invecchiamento, Università di Pisa, Italy.

Address correspondence to Alessio Donati, PhD, Università di Pisa, Centro di Ricerca Biologia e Patologia dell'Invecchiamento, Roma 55, Pisa, Italy 56126. E-mail: a.donati{at}med.unipi.it

Autophagy is a process that sequesters and degrades altered organelles and macromolecular cytoplasmic constituents for cellular restructuring and repair, and as a source of nutrients for metabolic use in early starvation it may be involved in anti-aging mechanisms of caloric restriction. The effects of 40% daily dietary restriction (DR) and intermittent feeding (EOD) on the age-related changes in the endocrine regulation of autophagic proteolysis were studied by monitoring the rate of valine release from isolated rat liver cells. Results show that in ad libitum-fed rats sensitivity of autophagy to glucagon and insulin declines by one order of magnitude in older rats. Both DR and EOD maintain the sensitivity to glucagon at juvenile levels, whereas only EOD can fully maintain response to insulin. It is concluded that changes in the sensitivity to glucagon may have a role in the aging process.

Key Words: Autophagy • Caloric restriction • Aging • Insulin • Glucagon

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