Dietary restriction initiated in late adulthood can reverse age-related alterations of protein and protein metabolism

Many reports have been published on the effects of lifelong dietary restriction (DR) on a variety of parameters such as life span, carcinogenesis, immunosenescence, memory function, and oxidative stress. There is, however, limited available information on the effect of late onset DR that might have potential application to intervene in human aging. We have investigated the effect of DR initiated late in life on protein and protein degradation. Two months of DR in 23.5-month-old mice significantly reduced heat-labile altered proteins in the liver, kidney, and brain. DR reversed the age-associated increase in the half-life of proteins, suggesting that the dwelling time of the proteins is reduced in DR animals. In accordance with this observation, the activity of proteasome, which is suggested to be responsible for degradation of altered proteins, was found increased in the liver of rats 30 months of age subjected to 3.5 months of DR. Thus, DR can increase turnover of proteins, thereby possibly attenuating potentially harmful consequences by altered proteins. Likewise, DR in old rats reduced carbonylated proteins in liver mitochondria, although the effect was not observed in cytosolic proteins. Fasting induced apoA-IV synthesis in the liver of young mice for efficient mobilization of stored tissue fats, while it occurred only marginally in the old. DR for 2 months from 23 months of age partially restored inducibility of this protein, suggesting the beneficial effect of DR. Taking all these findings together, it is conceivable that DR conducted in old age can be beneficial not only to retard age-related functional decline but also to restore functional activity in young rodents. Interestingly, recent evidence that involves DNA array gene expression analysis supports the findings on the age-related decrease in protein turnover and its reversion by late-onset DR.