It is an ongoing debate among researchers about the difference in life expectancy between men and women. Sociological explanations based on behavioral differences have been ruled out, leaving many possibly contributing mechanisms. The genetic associations with longevity are stronger in females than in males, according to a recent open access paper. This supports the theory that selection pressure emerged for women to live longer, driven by the support they provided to the reproductive fitness of their immediate descendants. The study also explores how sex-specific genes and pathways affect the differences in longevity between men and women. This discovery may shed light on the evolution of human longevity and why genetic associations with longevity are on average stronger in females.
Our Results Beg the Question of Why Genetic Associations with Longevity are Stronger in Women?
In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians.
The fact that females take much more care for childbearing and offspring than males may shed light on answering this question. Studies related to age-specific manifestation of genetic load suggest that fertility serves as the major factor of Darwinian natural selection for the accumulation of genetic mutation driving population survival and growth. The grandmother hypothesis proposed that postmenopausal longevity in human evolved from grandmothers’ assistance with childcare, which prolonged females’ lifespan. A study reported that female centenarians were four times more likely to have children in their forties than females who lived only to age 73. Other studies (including analyses based on the CLHLS datasets) also found that females’ late childbearing after ages 35 or 40 is positively and significantly associated with longevity. A study indicated that the longevity advantage of females over males may be a by-product of genetic evolution that maximizes the length of time during which females could bear and take care of children and contribute to human reproduction. The reproductive function of females might serve as a driving force for positive selection on the human genome and the related physiological features, such as immune response and metabolism. During periods of stress such as starvation, females use available amino acids to create deposits in the liver to support reproduction; conversely males slow down anabolic pathways and reserve carbohydrate stores for eventual use by the musculature.
