Effect of dietary restriction beyond middle age: Accumulation of altered proteins and protein degradation

Dietary restriction (DR) from weaning or young adult stages in rodents throughout their usual life span has been shown to prolong longevity and lower or delay (or both) the occurrence of many late-onset diseases, but the effects of DR when performed at middle age or later have not been well investigated. We have studied the effect of DR initiated late in life on altered proteins and protein degradation. DR initiated in 23.5-month-old mice and continued for 2 months reduced the amount of altered proteins and shortened the half-life of proteins, including oxidatively modified ones. Furthermore, our more recent studies in rats demonstrated that DR initiated later in life (26.5 months old) restored the activities of proteasomes that have been implicated in removal of altered proteins. Thus, DR initiated even relatively late in life appears to have beneficial effects, restoring an animal's youthful condition in terms of the age-related accumulation of altered proteins.