TY - JOUR
T1 - Males induce premature demise of the opposite sex by multifaceted strategies
AU - Booth, Lauren N.
AU - Shi, Cheng
AU - Tantilert, Cindy
AU - Yeo, Robin W.
AU - Miklas, Jason W.
AU - Hebestreit, Katja
AU - Hollenhorst, Cecilia N.
AU - Maures, Travis J.
AU - Buckley, Matthew T.
AU - Murphy, Coleen T.
AU - Brunet, Anne
N1 - Funding Information:
We thank A. Villeneuve, M. Goodman and L. Bianchi for helpful discussions. Thank you to all the members of the Brunet lab, particularly J. Chen, S. Mahmoudi, A. McKay and K. Papsdorf for helpful feedback and discussion. Thank you to the members of the Murphy lab for valuable feedback. The Stanford Functional Genomics Facility performed the sequencing of the RNA-seq libraries. We thank the Caenorhabditis Genetics Center (funded by National Institutes of Health (NIH) grant P40 OD010440), L. Bianchi, A. Dillin, R. Dowen, M. Goodman and M.-W. Tan for providing C. elegans strains and we thank WormBase. This work was funded by R01AG054201 (A.B.), HHMI-Simons Faculty Scholars Program (C.T.M.), Glenn Foundation for Medical Research (C.T.M.), Genentech Foundation Predoctoral Fellowship (R.W.Y.), the Helen Hay Whitney Foundation (L.N.B.) and NIH K99 AG051738 (L.N.B.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/9
Y1 - 2022/9
N2 - Interactions between the sexes negatively impact health in many species. In Caenorhabditis, males shorten the lifespan of the opposite sex—hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved in male-induced demise in C. elegans. Some genes (for example, delm-2, acbp-3), when knocked down, are specifically protective against male-induced demise. Others (for example, sri-40), when knocked down, extend lifespan with and without males, suggesting general mechanisms of protection. In contrast, many classical long-lived mutants are impacted more negatively than wild type by the presence of males, highlighting the importance of sexual environment for longevity. Interestingly, genes induced by males are triggered by specific male components (seminal fluid, sperm and pheromone), and manipulating these genes in combination in hermaphrodites induces stronger protection. One of these genes, the conserved ion channel delm-2, acts in the nervous system and intestine to regulate lipid metabolism. Our analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers elaborate strategies elicited by sexual interactions that could extend to other species.
AB - Interactions between the sexes negatively impact health in many species. In Caenorhabditis, males shorten the lifespan of the opposite sex—hermaphrodites or females. Here we use transcriptomic profiling and targeted screens to systematically uncover conserved genes involved in male-induced demise in C. elegans. Some genes (for example, delm-2, acbp-3), when knocked down, are specifically protective against male-induced demise. Others (for example, sri-40), when knocked down, extend lifespan with and without males, suggesting general mechanisms of protection. In contrast, many classical long-lived mutants are impacted more negatively than wild type by the presence of males, highlighting the importance of sexual environment for longevity. Interestingly, genes induced by males are triggered by specific male components (seminal fluid, sperm and pheromone), and manipulating these genes in combination in hermaphrodites induces stronger protection. One of these genes, the conserved ion channel delm-2, acts in the nervous system and intestine to regulate lipid metabolism. Our analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers elaborate strategies elicited by sexual interactions that could extend to other species.
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U2 - 10.1038/s43587-022-00276-y
DO - 10.1038/s43587-022-00276-y
M3 - Article
C2 - 37118502
AN - SCOPUS:85138154217
SN - 2662-8465
VL - 2
SP - 809
EP - 823
JO - Nature Aging
JF - Nature Aging
IS - 9
ER -