Pan-tissue Transcriptome Analysis Reveals Sex-dimorphic Human Aging
Abstract
Complex diseases often exhibit sex-dimorphism in morbidity and prognosis, many of which are age-related. However, the underlying mechanisms of sex-dimorphic aging remain foggy, with limited studies across multiple tissues. We systematically analyzed ~17,000 transcriptomes from 35 human tissues to quantitatively evaluate the individual and combined contributions of sex and age to transcriptomic variations. We discovered extensive sex-dimorphisms during aging with distinct patterns of change in gene expression and alternative splicing (AS). Intriguingly, the male-biased age-associated AS events have a stronger association with Alzheimer's disease, and the female-biased events are often regulated by several sex-biased splicing factors that may be controlled by estrogen receptors. Breakpoint analysis showed that sex-dimorphic aging rates are significantly associated with decline of sex hormones, with males having a larger and earlier transcriptome change. Collectively, this study uncovered an essential role of sex during aging at the molecular and multi-tissue levels, providing insight into sex-dimorphic regulatory patterns.
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Research summary
The paper claims that sex-dimorphic aging patterns are associated with distinct gene expression changes and alternative splicing events influenced by sex hormones. This research is relevant as it explores the molecular mechanisms underlying aging, specifically how sex differences contribute to aging processes, which could inform strategies for longevity and age-related disease prevention.
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