Changes in gene expression associated with aging commonly originate during juvenile growth

In mammals, proliferation is rapid in many tissues during early postnatal life, causing rapid somatic growth. This robust proliferation is then suppressed as the animal approaches adult size, bringing many tissues to a quiescent state where proliferation occurs only as needed to replace dying cells. Recent evidence suggests that the mechanism responsible for this decline in proliferation involves a multi-organ genetic program. We hypothesized that this genetic program continues to progress into later adult life, eventually suppressing proliferation to levels below those needed for tissue renewal, thus contributing to aging. We therefore used expression microarray to compare the temporal changes in gene expression that occur in adult mouse organs during aging to those occurring as juvenile proliferation slows. We found that many of the changes in gene expression that occur during the aging process originate during the period of juvenile growth deceleration. Bioinformatic analyses of the genes that show persistent decline in expression throughout postnatal life indicated that cell-cycle-related genes are strongly over-represented. Thus, the findings support the hypothesis that the genetic program that slows juvenile growth to limit body size persists into adulthood and thus may eventually hamper tissue maintenance and repair, contributing to the aging process.

Research highlights▶ Proliferation in juvenile life is slowed by a genetic program to limit body size. ▶ Part of this program continues to progress in adult life, contributing to aging. ▶ Delaying the program, perhaps in condition like caloric restriction, may slow aging. ▶ Aging may be a lingering consequence of the evolutionary need to limit body size.