Beneficial biochemical outcomes of late-onset dietary restriction in rodents

Dietary restriction (DR) or caloric restriction (CR) is the well-established means to retard aging, leading to prolongation of mean and maximum life span in many animal models.We have been interested in the possibility of extending the span of health of elderly people rather than increasing longevity, and therefore studied the effects of DR/CR initiated late in life in rodent models. We restricted food for 2-3.5 months in mice or rats of middle or old ages, which would perhaps be equivalent to 50-70 years of age in humans. We found that: (1) Potentially harmful altered proteins were reduced in the animals' tissues. (2) Extended half-life of protein in aged animals was shortened in mouse hepatocytes, suggesting improved protein turnover. (3) Reduced proteasome activity was upregulated in rat liver and skeletal muscle. (4) Protein carbonyls were decreased in rat liver mitochondria and skeletal muscle cytoplasm, and also oxidative DNA damage was reduced in rat liver nucleus, suggesting amelioration of oxidative stress. (5) Reduced apo A-IV and C-III metabolism in aged mouse was restored, suggesting increase in reduced fatty acid mobilization. (6) The carbonyl modification in histones that was paradoxically reduced in aged ratwas increased to the level of a young animal, suggesting restoration of reduced transcription. These findings in rodents suggest a possibility that DR/CR is beneficial if applied in middle-aged or early senescent obese people. We argue, however, that application of late life DR/CR can be harmful if practiced in people who are already eating modestly.