The effect of caloric restriction on lipofuscin accumulation in mouse brain with age.

Caloric restriction (CR), has been shown to extend average and maximum lifespan in rodents and other animals as well as to delay a wide variety of manifestations of aging. The purpose of this study was to further elucidate the relationship between lipofuscin (LF) accumulation and the aging process by examining the effect of lifelong CR on LF accumulation in brain cells. Specifically, 1) we include age groups of CR (CR1 approximately equal to 90 kcal/wk and CR2 approximately equal to 58 kcal/wk) and ad libidum fed (AL; approximately 120 kcal/wk) mice including groups at maximum lifespan; 2) CR was the major dietary manipulation; 3) LF was identified using EM; 4) LF was quantified by areal measurement; and 5) the results were analyzed by inferential statistics. We have found that 1) LF increased with age and 2) that animals in the CR2 group had significantly less overall LF in the perikarya of the granule cells of the dentate gyrus when compared to CR1 or AL animals at equivalent ages. In addition, CR2 mice at maximum lifespan (45 mo.) had slightly less LF than did CR1 or AL mice at their maximum lifespans (36 mo.). Our results clearly demonstrate that CR (at 52%, but not 25% of AL diet) retards the overall accumulation of LF with time and, further, suggest that LF accumulation is not simply a linear function of age.