TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging.

TitleTGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging.
Publication TypeJournal Article
Year of Publication2009
AuthorsLuo S, Shaw WM, Ashraf J, Murphy CT
JournalPLoS Genet
Volume5
Issue12
Paginatione1000789
Date Published2009 Dec
ISSN1553-7404
KeywordsAging, Animals, Body Size, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Diet, Female, Longevity, Male, Mutation, Ovulation, Reproduction, Signal Transduction, Spermatozoa, Transforming Growth Factor beta
Abstract

Female reproductive cessation is one of the earliest age-related declines humans experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans' reproductive span is short relative to its total life span, with reproduction ceasing about a third into its 15-20 day adulthood. All of the known mutations and treatments that extend C. elegans' reproductive period also regulate longevity, suggesting that reproductive span is normally linked to life span. C. elegans has two canonical TGF-beta signaling pathways. We recently found that the TGF-beta Dauer pathway regulates longevity through the Insulin/IGF-1 Signaling (IIS) pathway; here we show that this pathway has a moderate effect on reproductive span. By contrast, TGF-beta Sma/Mab signaling mutants exhibit a substantially extended reproductive period, more than doubling reproductive span in some cases. Sma/Mab mutations extend reproductive span disproportionately to life span and act independently of known regulators of somatic aging, such as Insulin/IGF-1 Signaling and Dietary Restriction. This is the first discovery of a pathway that regulates reproductive span independently of longevity and the first identification of the TGF-beta Sma/Mab pathway as a regulator of reproductive aging. Our results suggest that longevity and reproductive span regulation can be uncoupled, although they appear to normally be linked through regulatory pathways.

DOI10.1371/journal.pgen.1000789
Alternate JournalPLoS Genet.
PubMed ID20041217
PubMed Central IDPMC2791159