Age-related changes in the autophagic proteolysis of rat isolated liver cells: Effects of antiaging dietary restrictions

Autophagy is a process that sequesters and degrades organelles and macromol ecular constituents of cytoplasm for cellular restructuring and repair and as a source of nutrients for metabolic use in early starvation. The effects of two antiaging dietary regimens (initiated in rats at the age of 2 month s), namely, 40% dietary restriction (DR) and every-other-day ad-libitum fee ding, that exhibited different effects on metabolism and similar effects on longevity on the age-related changes in the regulation of autophagic prote olysis were studied by monitoring the rate of valine release in the incubat ion medium from isolated liver cells of male albino Sprague-Dawley rats age d 2, 6, 12, 18, 24, and 27 months. (The liver cells were incubated in vitro with added amino acids and 10(-7) M insulin or glucagon.) Age-matched male albino Sprague-Dawley rats fed ad libitum served as a control. Results sho w that in ad-libitum-fed rats, after a transient increase by age 6 months, autophagic proteolysis and regulation by amino acid exhibit a dramatic age- related decline, and that the age-related changes are prevented by dietary antiaging intervention. A comparison shows that the protective effects of D R and every-other-day ad-libitum feeding are partially different in 24-mont h-old rats (but the beneficial effects of the two diets on regulation of au tophagic proteolysis are always similar). With regard to endocrine regulati on, results confirm that the liver cell response to glucagon (but not to in sulin) declines with increasing age, and they show that antiaging DRs signi ficantly improve the effects of glucagon (and have no effect on the respons e to insulin). The interactions of age by diet, glucagon (and in older rats , insulin), and amino acids are significant. It is concluded that DR signif icantly improves the susceptibility of liver cells to lysosomal degradation , and it prevents decline with increasing age. It is suggested that improve d liver autophagy and lysosomal degradation might be part of the antiaging mechanisms of DR.