Work

Evidence for the role of selection for reproductively advantageous alleles in human aging

Year: 2023

Type: article

Abstract: ABSTRACT The antagonistic pleiotropy hypothesis posits that natural selection for pleiotropic mutations that confer earlier or more reproduction but impair the post-reproductive life causes aging. This hypothesis of the evolutionary origin of aging is supported by case studies but lacks unambiguous genomic evidence. Here we genomically test this hypothesis using the genotypes, reproductive phenotypes, and death registry of 276,406 UK Biobank participants. We observe a strong, negative genetic correlation between reproductive traits and lifespan. Individuals with higher polygenetic scores for reproduction ( PGS R ) have lower survivorships to age 76 ( SV 76 ), and PGS R increased over birth cohorts from 1940 to 1969. Similar trends are found from individual genetic variants examined. PGS R and SV 76 remain negatively correlated upon the control of the offspring number, revealing horizontal pleiotropy between reproduction and lifespan. Intriguingly, regardless of PGS R , having two children maximizes SV 76 . These and other findings strongly support the antagonistic pleiotropy hypothesis of aging in humans.

Source: Science Advances

DOI: 10.1126/sciadv.adh4990

Authors: Erping Long, Jianzhi Zhang

Institutions: National Institutes of Health, Chinese Academy of Medical Sciences & Peking Union Medical College, University of Michigan, Division of Cancer Epidemiology and Genetics, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences

Language: English

Topic: Genetics, Aging, and Longevity in Model Organisms

Subfield: Aging

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,500