Pan-tissue transcriptome analysis reveals sex-dimorphic human aging.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41042139.
- Also identified by DOI 10.7554/eLife.102449 and PMC identifier 12494380.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Aging
- Sex Characteristics
- Gene Expression Profiling
- Transcriptome