Caloric restriction (CR), has been shown to extend average and maximum
lifespan in rodents and other animals as well as to delay a wide vari
ety of manifestations of aging. The purpose of this study was to furth
er elucidate the relationship between lipofuscin (LF) accumulation and
the aging process by examining the effect of lifelong CR on LF accumu
lation in brain cells. Specifically, 1) we include age groups of CR (C
RI congruent to 90 kcal/wk and CR2 congruent to 58 kcal/wk) and ad lib
idum fed (AL; similar to 120 kcal/wk) mice including groups at maximum
lifespan; 2) CR was the major dietary manipulation; 3) LF was identif
ied using EM; 4) LF was quantified by areal measurement; and 5) the re
sults were analyzed by inferential statistics. We have found that 1) L
F increased with age and 2) that animals in the CR2 group had signific
antly less overall LF in the perikarya of the granule cells of the den
tate gyrus when compared to CR1 or AL animals at equivalent ages. In a
ddition, CR2 mice at maximum lifespan (45 mo.) had slightly less LF th
an 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.