The protection of rat liver autophagic proteolysis from the age-related decline co-varies with the duration of anti-ageing food restriction

Restricting caloric intake (CR) well below that of ad libitum (AL) fed anim als retards and/or delays many characteristics of ageing and the occurrence and progression of age-associated diseases, efficacy depending on duration . The hypothesis that the anti-ageing effect of CR might involve stimulatio n of the cell-repair mechanism autophagy was tested. The effects of ageing and duration of anti-ageing CR on liver autophagic proteolysis (AP) were ex plored in male AL Sprague-Dawley rats aged 2-, 6-, 12- and 24-months; and 2 4-month-old rats on a CR diet initiated at 2-, 6- and 12-month of age or in itiated at age 2-months and interrupted at age 18 months. The age-related c hanges in the regulation of AP were studied by monitoring the rate of valin e release in the incubation medium from isolated liver cells by an HPLC pro cedure. Results show that the maximum attainable rate and the regulation of AP decline with increasing age; that changes are prevented by anti-ageing CR initiated at young age, that the protective effects of CR change with th e duration of diet. It is concluded that the data are compatible with the h ypothesis that AP and improved membrane maintenance might be involved in th e antiageing mechanism of CR. (C) 2001 Elsevier Science Inc. All rights res erved.