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Gene pathways that delay Caenorhabditis elegans reproductive senescence.

Wang MC, Oakley HD, Carr CE, Sowa JN, Ruvkun G - PLoS Genet. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Reproductive longevity extending effects in mated animals.(A) 19 gene inactivations only in hermaphrodites but not males extend the reproductive lifespan of mated hermaphrodites. (B) 11 genes extend reproductive lifespan when inactivated in both hermaphrodites and males. (C) Five gene inactivations in males alone are sufficient to increase the reproductive lifespan of mated hermaphrodites. * p<0.05, ** p<0.01, ***p<0.005. (D) daf-2 RNAi inactivation only in males prolongs reproductive lifespan of mated wild type hermaphrodites by 37% (p<0.001), but fails to do so in the mated daf-16(mgDf50) mutant hermaphrodites (p = 0.79).
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pgen-1004752-g004: Reproductive longevity extending effects in mated animals.(A) 19 gene inactivations only in hermaphrodites but not males extend the reproductive lifespan of mated hermaphrodites. (B) 11 genes extend reproductive lifespan when inactivated in both hermaphrodites and males. (C) Five gene inactivations in males alone are sufficient to increase the reproductive lifespan of mated hermaphrodites. * p<0.05, ** p<0.01, ***p<0.005. (D) daf-2 RNAi inactivation only in males prolongs reproductive lifespan of mated wild type hermaphrodites by 37% (p<0.001), but fails to do so in the mated daf-16(mgDf50) mutant hermaphrodites (p = 0.79).

Mentions: Self-fertilizing C. elegans hermaphrodites generate a limited number of sperm by virtue of a pulse of spermatogenesis before a longer run of oogenesis, which constrains their reproductive capacities. However when mated to males which produce far more sperm over a longer period, hermaphrodites use male sperm preferentially, produce double the number of progeny, and reproduce for a much longer time period [7]. To test whether the newly identified genes exert effects on the reproductive longevity of mated animals, we first inactivated these genes in hermaphrodites by RNAi and then crossed those animals with males feeding with control bacteria expressing no dsRNAs. Under this condition, sperm from the males are not affected by RNAi inactivation. We found that 19 genes when inactivated only in mated hermaphrodites are sufficient to promote reproductive longevity (Figure 4A and Table S5), suggesting that these gene inactivations predominantly delay age-associated oocyte senescence.


Gene pathways that delay Caenorhabditis elegans reproductive senescence.

Wang MC, Oakley HD, Carr CE, Sowa JN, Ruvkun G - PLoS Genet. (2014)

Reproductive longevity extending effects in mated animals.(A) 19 gene inactivations only in hermaphrodites but not males extend the reproductive lifespan of mated hermaphrodites. (B) 11 genes extend reproductive lifespan when inactivated in both hermaphrodites and males. (C) Five gene inactivations in males alone are sufficient to increase the reproductive lifespan of mated hermaphrodites. * p<0.05, ** p<0.01, ***p<0.005. (D) daf-2 RNAi inactivation only in males prolongs reproductive lifespan of mated wild type hermaphrodites by 37% (p<0.001), but fails to do so in the mated daf-16(mgDf50) mutant hermaphrodites (p = 0.79).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256158&req=5

pgen-1004752-g004: Reproductive longevity extending effects in mated animals.(A) 19 gene inactivations only in hermaphrodites but not males extend the reproductive lifespan of mated hermaphrodites. (B) 11 genes extend reproductive lifespan when inactivated in both hermaphrodites and males. (C) Five gene inactivations in males alone are sufficient to increase the reproductive lifespan of mated hermaphrodites. * p<0.05, ** p<0.01, ***p<0.005. (D) daf-2 RNAi inactivation only in males prolongs reproductive lifespan of mated wild type hermaphrodites by 37% (p<0.001), but fails to do so in the mated daf-16(mgDf50) mutant hermaphrodites (p = 0.79).
Mentions: Self-fertilizing C. elegans hermaphrodites generate a limited number of sperm by virtue of a pulse of spermatogenesis before a longer run of oogenesis, which constrains their reproductive capacities. However when mated to males which produce far more sperm over a longer period, hermaphrodites use male sperm preferentially, produce double the number of progeny, and reproduce for a much longer time period [7]. To test whether the newly identified genes exert effects on the reproductive longevity of mated animals, we first inactivated these genes in hermaphrodites by RNAi and then crossed those animals with males feeding with control bacteria expressing no dsRNAs. Under this condition, sperm from the males are not affected by RNAi inactivation. We found that 19 genes when inactivated only in mated hermaphrodites are sufficient to promote reproductive longevity (Figure 4A and Table S5), suggesting that these gene inactivations predominantly delay age-associated oocyte senescence.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.