title: Gene pathways that delay Caenorhabditis elegans reproductive senescence.
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.
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Meng C
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Holly D
authors.initials: HD
authors.lastname: Oakley
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Carr
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Sowa
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D055106:Genome-Wide Association Study; D008136:Longevity / Q000235:genetics*; D008297:Male; D034622:RNA Interference; D012098:Reproduction / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics