Reversible effects of long-term caloric restriction on protein oxidative damage

The age-associated increase in oxidative damage in ad libitum-fed mice is a ttenuated in mice fed calorically restricted (CR) diets. The objective of t his study was to determine if this effect results from a slowing of age-rel ated accumulation of oxidative damage, or from a reversible decrease of oxi dative damage by caloric restriction. To address these possibilities, cross over studies were conducted in C57BL/6 mice aged 15 to 22 months that had b een maintained, after 4 months of age, on ad libitum (AL) or a 60% of AL ca loric regimen. One half of the mice in these groups were switched to the op posite regimen of caloric intake for periods up to 6 weeks, and protein oxi dative damage (measured as carbonyl concentration and loss of sulfhydryl co ntent) was measured in homogenates of brain and heart. In AL-fed mice, the protein carbonyl content increased with age, whereas the sulfhydryl content decreased. Old mice maintained continuously under CR had reduced levels of protein oxidative damage when compared with the old mice fed AL. The effec ts of chronic CR on the carbonyl content of the whole brain and the sulfhyd ryl content of the heart were fully reversible within 3-6 weeks following r einstatement of AL feeding. The effect of chronic CR on the sulfhydryl cont ent of the brain cortex was only partially reversible. The introduction of CR for 6 weeks in the old mice resulted in a reduction of protein oxidative damage (as indicated by whole brain carbonyl content and cortex sulfhydryl ), although this effect was not equivalent to that of CR from 4 months of a ge. The introduction of CR did not affect the sulfhydryl content of the hea rt. Overall, the current findings indicate that changes in the level of cal oric intake may reversibly affect the concentration of oxidized proteins an d sufhydryl content. In addition, chronic restriction of caloric intake als o retards the age-associated accumulation of oxidative damage. The magnitud e of the reversible and chronic effects appears to be dependent upon the ti ssue examined and the nature of the oxidative alteration.