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Gene pathways that delay Caenorhabditis elegans reproductive senescence.
- Source :
-
PLoS genetics [PLoS Genet] 2014 Dec 04; Vol. 10 (12), pp. e1004752. Date of Electronic Publication: 2014 Dec 04 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Reproductive senescence is a hallmark of aging. The molecular mechanisms regulating reproductive senescence and its association with the aging of somatic cells remain poorly understood. From a full genome RNA interference (RNAi) screen, we identified 32 Caenorhabditis elegans gene inactivations that delay reproductive senescence and extend reproductive lifespan. We found that many of these gene inactivations interact with insulin/IGF-1 and/or TGF-β endocrine signaling pathways to regulate reproductive senescence, except nhx-2 and sgk-1 that modulate sodium reabsorption. Of these 32 gene inactivations, we also found that 19 increase reproductive lifespan through their effects on oocyte activities, 8 of them coordinate oocyte and sperm functions to extend reproductive lifespan, and 5 of them can induce sperm humoral response to promote reproductive longevity. Furthermore, we examined the effects of these reproductive aging regulators on somatic aging. We found that 5 of these gene inactivations prolong organismal lifespan, and 20 of them increase healthy life expectancy of an organism without altering total life span. These studies provide a systemic view on the genetic regulation of reproductive senescence and its intersection with organism longevity. The majority of these newly identified genes are conserved, and may provide new insights into age-associated reproductive senescence during human aging.
- Subjects :
- Animals
Animals, Genetically Modified
Caenorhabditis elegans physiology
Female
Gene Expression Regulation
Gene Silencing
Genome-Wide Association Study
Male
RNA Interference
Signal Transduction genetics
Aging genetics
Caenorhabditis elegans genetics
Gene Regulatory Networks
Longevity genetics
Reproduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 10
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 25474471
- Full Text :
- https://doi.org/10.1371/journal.pgen.1004752