title: The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans.
abstract: 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.
authors.affiliation: National Institute of Biological Sciences, Beijing, 102206 Beijing, People's Republic of China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008297:Male; D009154:Mutation; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D018510:RNA, Helminth / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D051858:Forkhead Transcription Factors; C452195:LIN-28 protein, C elegans; D018510:RNA, Helminth; D012097:Repressor Proteins; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin