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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.


Germline genetic inactivations that prolong reproductive lifespan.In the rrf-1(pk1417) mutant, RNAi predominantly operates in the germline. Ten of the identified genes increase reproductive lifespan when inactivated in the rrf-1 mutants. The extension levels are comparable to that in wild type (N2), except for daf-2, nhx-2 and moma-1. The average of three independent experiments is shown, p<0.05.
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pgen-1004752-g003: Germline genetic inactivations that prolong reproductive lifespan.In the rrf-1(pk1417) mutant, RNAi predominantly operates in the germline. Ten of the identified genes increase reproductive lifespan when inactivated in the rrf-1 mutants. The extension levels are comparable to that in wild type (N2), except for daf-2, nhx-2 and moma-1. The average of three independent experiments is shown, p<0.05.

Mentions: Reproductive activities are under the control of complex interaction between germline and somatic tissues. To test whether the candidate genes function in the germline or in somatic tissues to regulate reproductive longevity, we inactivated the 32 reproductive senescence genes in rrf-1(pk1417) mutant animals, for which RNAi is predominantly effective only in the germline with a minor effect in the intestine [22], [23]. We found that only 10 gene inactivations prolong the reproductive lifespan of the rrf-1 mutant animals (Figure 3 and Table sS4). Among them, the effect of nhx-2/sodium/hydrogen exchanger, moma-1/apolipoprotein O homologue or daf-2/insulin-like receptor in the rrf-1 background is much weaker than that in wild type (Figure 3), suggesting that their functions in somatic tissues are also involved in the regulation of reproductive longevity. Moreover, the other 22 gene inactivations failed to increase reproductive lifespan in the rrf-1 mutant; those genes likely regulate reproductive longevity systemically via their effects in somatic tissues. Together these studies indicate the significance of somatic functions in the regulation of reproductive senescence.


Gene pathways that delay Caenorhabditis elegans reproductive senescence.

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

Germline genetic inactivations that prolong reproductive lifespan.In the rrf-1(pk1417) mutant, RNAi predominantly operates in the germline. Ten of the identified genes increase reproductive lifespan when inactivated in the rrf-1 mutants. The extension levels are comparable to that in wild type (N2), except for daf-2, nhx-2 and moma-1. The average of three independent experiments is shown, p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1004752-g003: Germline genetic inactivations that prolong reproductive lifespan.In the rrf-1(pk1417) mutant, RNAi predominantly operates in the germline. Ten of the identified genes increase reproductive lifespan when inactivated in the rrf-1 mutants. The extension levels are comparable to that in wild type (N2), except for daf-2, nhx-2 and moma-1. The average of three independent experiments is shown, p<0.05.
Mentions: Reproductive activities are under the control of complex interaction between germline and somatic tissues. To test whether the candidate genes function in the germline or in somatic tissues to regulate reproductive longevity, we inactivated the 32 reproductive senescence genes in rrf-1(pk1417) mutant animals, for which RNAi is predominantly effective only in the germline with a minor effect in the intestine [22], [23]. We found that only 10 gene inactivations prolong the reproductive lifespan of the rrf-1 mutant animals (Figure 3 and Table sS4). Among them, the effect of nhx-2/sodium/hydrogen exchanger, moma-1/apolipoprotein O homologue or daf-2/insulin-like receptor in the rrf-1 background is much weaker than that in wild type (Figure 3), suggesting that their functions in somatic tissues are also involved in the regulation of reproductive longevity. Moreover, the other 22 gene inactivations failed to increase reproductive lifespan in the rrf-1 mutant; those genes likely regulate reproductive longevity systemically via their effects in somatic tissues. Together these studies indicate the significance of somatic functions in the regulation of reproductive 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.