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preLekára.sk / Odborné časopisy / PLOS Genetics / 2014 - 12

Gene Pathways That Delay Reproductive Senescence

English version České info

Female reproductive senescence is one hallmark of human aging, and as the germline ages, there is increased incidence of chromosome non-dysjunction and DNA damage. Delayed childbearing is a general feature in modern society, resulting in high risk of infertility, miscarriage and birth defects. Thus, understanding the molecular mechanisms regulating reproductive senescence and its association with somatic senescence is increasingly relevant to human health, and will shed light on the prolongation of reproductive longevity and the improvement of post-reproductive health. Here we conducted a genomic screen in Caenorhabditis elegans, searching for genetic regulators of reproductive senescence. We identified 32 gene inactivations that extend reproductive lifespan. Functional characterization of these genes has revealed their interactions with insulin/IGF-1 and TGF-β signaling pathways, their effects in different genders on the regulation of reproductive longevity, and their implications in the control of healthy life expectancy. Many of these genes are conserved between worms and humans. Our studies thus provide new insights into the molecular control of reproductive aging and the mechanistic link between reproductive senescence and organism longevity.

Vyšlo v časopise: Gene Pathways That Delay Reproductive Senescence. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004752
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004752

Souhrn

Female reproductive senescence is one hallmark of human aging, and as the germline ages, there is increased incidence of chromosome non-dysjunction and DNA damage. Delayed childbearing is a general feature in modern society, resulting in high risk of infertility, miscarriage and birth defects. Thus, understanding the molecular mechanisms regulating reproductive senescence and its association with somatic senescence is increasingly relevant to human health, and will shed light on the prolongation of reproductive longevity and the improvement of post-reproductive health. Here we conducted a genomic screen in Caenorhabditis elegans, searching for genetic regulators of reproductive senescence. We identified 32 gene inactivations that extend reproductive lifespan. Functional characterization of these genes has revealed their interactions with insulin/IGF-1 and TGF-β signaling pathways, their effects in different genders on the regulation of reproductive longevity, and their implications in the control of healthy life expectancy. Many of these genes are conserved between worms and humans. Our studies thus provide new insights into the molecular control of reproductive aging and the mechanistic link between reproductive senescence and organism longevity.

Zdroje

1. BroekmansFJ, KnauffEA, te VeldeER, MacklonNS, FauserBC (2007) Female reproductive ageing: current knowledge and future trends. Trends Endocrinol Metab 18 : 58–65.

2. te VeldeER, PearsonPL (2002) The variability of female reproductive ageing. Hum Reprod Update 8 : 141–154.

3. TreloarAE (1981) Menstrual cyclicity and the pre-menopause. Maturitas 3 : 249–264.

4. de BruinJP, BovenhuisH, van NoordPA, PearsonPL, van ArendonkJA, et al. (2001) The role of genetic factors in age at natural menopause. Hum Reprod 16 : 2014–2018.

5. MurabitoJM, YangQ, FoxC, WilsonPW, CupplesLA (2005) Heritability of age at natural menopause in the Framingham Heart Study. J Clin Endocrinol Metab 90 : 3427–3430.

6. van AsseltKM, KokHS, PearsonPL, DubasJS, PeetersPH, et al. (2004) Heritability of menopausal age in mothers and daughters. Fertil Steril 82 : 1348–1351.

7. HughesSE, EvasonK, XiongC, KornfeldK (2007) Genetic and pharmacological factors that influence reproductive aging in nematodes. PLoS Genet 3: e25.

8. LuoS, KleemannGA, AshrafJM, ShawWM, MurphyCT (2010) TGF-beta and insulin signaling regulate reproductive aging via oocyte and germline quality maintenance. Cell 143 : 299–312.

9. LuoS, ShawWM, AshrafJ, MurphyCT (2009) TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic aging. PLoS Genet 5: e1000789.

10. HamataniT, FalcoG, CarterMG, AkutsuH, StaggCA, et al. (2004) Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet 13 : 2263–2278.

11. PelosiE, OmariS, MichelM, DingJ, AmanoT, et al. (2013) Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice. Nat Commun 4 : 1843.

12. PartridgeL, ProwseN, PignatelliP (1999) Another set of responses and correlated responses to selection on age at reproduction in Drosophila melanogaster. Proc Biol Sci 266 : 255–261.

13. RoseMR (1984) Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution 38 : 1004–1010.

14. LuckinbillLS, ArkingR, ClareMJ, CiroccoWC, BuckSA (1984) Selection for delayed senescence in Drosophila melanogaster. Evolution 38 : 996–1003.

15. PartridgeL, FowlerK (1992) Direct and correlated response to selection on age at reproduction in Drosophila melanogaster. Evolution 46 : 76–91.

16. Emery ThompsonM, JonesJH, PuseyAE, Brewer-MarsdenS, GoodallJ, et al. (2007) Aging and fertility patterns in wild chimpanzees provide insights into the evolution of menopause. Curr Biol 17 : 2150–2156.

17. JacobsenBK, HeuchI, KvaleG (2003) Age at natural menopause and all-cause mortality: a 37-year follow-up of 19,731 Norwegian women. Am J Epidemiol 157 : 923–929.

18. PerlsTT, AlpertL, FrettsRC (1997) Middle-aged mothers live longer. Nature 389 : 133.

19. SchmitzC, KingeP, HutterH (2007) Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc Natl Acad Sci U S A 104 : 834–839.

20. LoffingJ, FloresSY, StaubO (2006) Sgk kinases and their role in epithelial transport. Annu Rev Physiol 68 : 461–490.

21. OrlowskiJ, GrinsteinS (1997) Na+/H+ exchangers of mammalian cells. J Biol Chem 272 : 22373–22376.

22. SmardonA, SpoerkeJM, StaceySC, KleinME, MackinN, et al. (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10 : 169–178.

23. KumstaC, HansenM (2012) C. elegans rrf-1 mutations maintain RNAi efficiency in the soma in addition to the germline. PLoS One 7: e35428.

24. PletcherSD, KhazaeliAA, CurtsingerJW (2000) Why do life spans differ? Partitioning mean longevity differences in terms of age-specific mortality parameters. J Gerontol A Biol Sci Med Sci 55: B381–389.

25. HertweckM, GobelC, BaumeisterR (2004) C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 6 : 577–588.

26. NehrkeK (2003) A reduction in intestinal cell pHi due to loss of the Caenorhabditis elegans Na+/H+ exchanger NHX-2 increases life span. J Biol Chem 278 : 44657–44666.

27. SalkerMS, ChristianM, SteelJH, NautiyalJ, LaveryS, et al. (2011) Deregulation of the serum -⁠ and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure. Nat Med 17 : 1509–1513.

28. KuwabaraPE (2003) The multifaceted C. elegans major sperm protein: an ephrin signaling antagonist in oocyte maturation. Genes Dev 17 : 155–161.

29. MauresTJ, BoothLN, BenayounBA, IzrayelitY, SchroederFC, et al. (2014) Males shorten the life span of C. elegans hermaphrodites via secreted compounds. Science 343 : 541–544.

30. ShiC, MurphyCT (2014) Mating induces shrinking and death in Caenorhabditis mothers. Science 343 : 536–540.

31. Sacher GA (1977) Life table modification and life prolongation. In: Finch CE, Hayflick L, editors. Handbook of the Biology of Aging. New York: Van Nostrand Reinhold Co. pp. 582–638.

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PLOS Genetics

2014 Číslo 12
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