Like other biological processes, aging is regulated by genetic pathways. However, it remains largely unknown whether aging is determined by an innate programmed timing mechanism and, if so, how this timer is linked to the mechanisms that control developmental timing. Here, we demonstrate that
sea-2, which encodes a zinc-finger protein, controls developmental timing in C. elegans larvae by regulating expression of the heterochronic gene
lin-28 at the post-transcriptional level.
lin-28 is also essential for the autosomal signal element (ASE) function of
sea-2 in X:A signal assessment. We also show that
sea-2 modulates aging in adulthood. Loss of function of
sea-2 slows the aging process and extends the adult lifespan in a DAF-16/FOXO-dependent manner. Mutation of
sea-2 promotes nuclear translocation of DAF-16 and subsequent activation of
daf-16 targets. We further demonstrate that insulin/IGF-1 signaling functions in the larval heterochronic circuit. Loss of function of the insulin/IGF-1 receptor gene
daf-2, which extends lifespan, also greatly enhances the retarded heterochronic defects in
sea-2 mutants. Regulation of developmental timing by
daf-2 requires
daf-16 activity. Our study provides evidence for intricate interplay between the heterochronic circuit that controls developmental timing in larvae and the timing mechanism that modulates aging in adults.