ArticleNature ecology & evolution2017
Antagonistic pleiotropy and mutation accumulation influence human senescence and disease.
Article in Nature ecology & evolution, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Multivariate genomic scan implicates novel loci and haem metabolism in human ageing.Nature communications · 2020Pooled it
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- Asynchrony of ageing among traits in a wild bird population.Evolution letters · 2026Article
- Evolutionary genetics of ageing.Nature reviews. Genetics · 2026Review
- Genetic trade-offs in fertility and longevity explain the maintenance of disease-associated alleles in humans.Nature ecology & evolution · 2026Article
- An antagonistically pleiotropic gene regulates vertebrate growth, maturity, and lifespan.Nature communications · 2026Article
- Extensive antagonistic variants across the human genome.Nature communications · 2026Article
- Overdominance for fitness: a genomic comparison between empirical and simulated data with Drosophila melanogaster.Genetics · 2026Article
- Chronic Kidney Disease and Cellular Senescence.International journal of molecular sciences · 2026Review
- The Spanish Polygenic Score reference distribution: a resource for personalized medicine.European journal of human genetics : EJHG · 2026Article
- Under the Shadow: Old-biased Genes Are Subject to Weak Purifying Selection at Both the Tissue- and Cell Type-Specific Levels.Genome biology and evolution · 2025Article
- Inbreeding load in finite populations from dominant and overdominant mutations.Proceedings. Biological sciences · 2025Article
- Estimation of Inbreeding Depression From Overdominant Loci Using Molecular Markers.Evolutionary applications · 2025Article
- Pleiotropy, epistasis and the genetic architecture of quantitative traits.Nature reviews. Genetics · 2024Review
- Senescence evolution under the catastrophic accumulation of deleterious mutations.Evolution letters · 2024Article
- More evidence for widespread antagonistic pleiotropy in polymorphic disease alleles.Frontiers in genetics · 2024Review
- Evidence for the role of selection for reproductively advantageous alleles in human aging.Science advances · 2023Article
- The evolution of aging and lifespan.Trends in genetics : TIG · 2023Review
- Evolutionary analysis of the mTOR pathway provide insights into lifespan extension across mammals.BMC genomics · 2023Article
- Pancreatic β-cell senescence in diabetes: mechanisms, markers and therapies.Frontiers in endocrinology · 2023Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescence has long been a public health challenge as well as a fascinating evolutionary problem. There is neither a universally accepted theory for its ultimate causes, nor a consensus about what may be its impact on human health. Here we test the predictions of two evolutionary explanations of senescence-mutation accumulation and antagonistic pleiotropy-which postulate that genetic variants with harmful effects in old ages can be tolerated, or even favoured, by natural selection at early ages. Using data from genome-wide association studies (GWAS), we study the effects of genetic variants associated with diseases appearing at different periods in life, when they are expected to have different impacts on fitness. Data fit theoretical expectations. Namely, we observe higher risk allele frequencies combined with large effect sizes for late-onset diseases, and detect a significant excess of early-late antagonistically pleiotropic variants that, strikingly, tend to be harboured by genes related to ageing. Beyond providing systematic, genome-wide evidence for evolutionary theories of senescence in our species and contributing to the long-standing question of whether senescence is the result of adaptation, our approach reveals relationships between previously unrelated pathologies, potentially contributing to tackling the problem of an ageing population.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.