Evolution of sex differences in lifespan and aging: causes and constraints
Abstract
Why do the two sexes have different lifespans and rates of aging? Two hypotheses based on asymmetric inheritance of sex chromosomes (“unguarded X”) or mitochondrial genomes (“mother's curse”) explain sex differences in lifespan as sex‐specific maladaptation leading to increased mortality in the shorter‐lived sex. While asymmetric inheritance hypotheses equate long life with high fitness, considerable empirical evidence suggests that sexes resolve the fundamental tradeoff between reproduction and survival differently resulting in sex‐specific optima for lifespan. However, selection for sex‐specific values in life‐history traits is constrained by intersexual genetic correlations resulting in intra‐locus sexual conflict over optimal lifespan. The available data suggest that the evolution of sexual dimorphism only partially resolves these conflicts. Sexual conflict over optimal trait values, which has been demonstrated in model organisms and in humans, is likely to play a key role in shaping the evolution of lifespan, as well as in maintaining genetic variation for sex‐specific diseases.
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The uni-parental inheritance of mitochondrial genomes may create genetic conflicts (sexual antagonistic pleiotropy) that cause mitochondrial functions, including PCD, to be particularly susceptible to aging-associated disruptions, including sex-biased mis-regulation.
“Finally, the uni-parental inheritance of mitochondrial genomes may create genetic conflicts (sexual antagonistic pleiotropy) that cause mitochondrial functions, including PCD, to be particularly susceptible to aging-associated disruptions, including sex-biased mis-regulation(Maklakov and Lummaa, 2013; Tower, 2006, 2014).”
From Programmed cell death in aging (2015) · cites this paper as Maklakov and Lummaa, 2013
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Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
mTOR is a key modulator of ageing and age-related disease
Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676 · see citing works
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120 · see citing works
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Sex differences in biological aging with a focus on human studies
Hägg, S., & Jylhävä, J. (2021) · eLife · doi:10.7554/elife.63425 · Cited by 442 · see citing works
Programmed cell death in aging
Tower, J. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.04.002 · Cited by 426 · see citing works
Sex-Specific Gene Expression and Life Span Regulation
Tower, J. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.07.002 · Cited by 118 · see citing works
- Authors
- Maklakov, A. A., & Lummaa, V.
- Affiliations
- Uppsala University (SE)
- University of Sheffield (GB)
- Corresponding author
- Maklakov, Alexei A.
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2013-06-03
- Volume
- 35
- Issue
- 8
- Pages
- 717-724
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- OpenAlex
- W2129869148
- Cited by
- 227
- References
- 3
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 7 · 2023: 13 · 2022: 17 · 2021: 23 · 2020: 19 · 2019: 18 · 2018: 24 · 2017: 21 · 2016: 17 · 2015: 15 · 2014: 24 · 2013: 5
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- BioEssays (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- sex differences in lifespan, aging, mitochondrial inheritance, sexual conflict, life-history trade-offs, sexual dimorphism, genetic variation
- MeSH terms
- Aging, Animals, Biological Evolution, Female, Humans, Longevity, Male, Mitochondria, Reproduction, Selection, Genetic, Sex Factors, Genetic Variation
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