Genetic and Pharmacological Factors That Influence Reproductive Aging in Nematodes 英文参考文献.docVIP

GeneticandPharmacologicalFactorsThat InfluenceReproductiveAginginNematodes Stacie E.Hughes1¤,Kimberley Evason1,Chengjie Xiong2,Kerry Kornfeld1* 1DepartmentofMolecularBiologyandPharmacology,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,2DivisionofBiostatistics, WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica Age-relateddegenerativechangesinthereproductivesystemareanimportantaspectofaging,becausereproductive successisthemajordeterminantofevolutionaryfitness.Caenorhabditiselegansisaprominentorganismforstudiesof somaticaging,sincemanyfactorsthatextendadultlifespanhavebeenidentified.However,mechanismsthatcontrol reproductive aging in nematodes or other animals are not well characterized. To use C. elegans to measure reproductive aging, we analyzed mated hermaphrodites that do not become sperm depleted and monitored the duration and level of progeny production. Mated hermaphrodites display a decline of progeny production that culminates in reproductive cessation before the end of the lifespan, demonstrating that hermaphrodites undergo reproductive aging. To identify factors that influence reproductive aging, we analyzed genetic, environmental, and pharmacological factors that extend lifespan. Dietary restriction and reduced insulin/insulin-like growth factor signaling delayed reproductive aging, indicating that nutritional status and a signaling pathway that responds to environmentalstressinfluencereproductiveaging.Coldtemperaturedelayedreproductiveaging.Theanticonvulsant medicineethosuximide,whichaffectsneuralactivity,delayedreproductiveaging,indicatingthatneuralactivitycan influence reproductive aging. Some of these factors decrease early progeny production, but there is no consistent relationship between early progeny production and reproductive aging in strains with an extended lifespan. To directly examine the effects of early progeny production on reproductive aging, we used sperm availability to modulat