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Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species

Early results, not yet checked by other scientists · bioRxiv · Oct 22, 2026

What this means

Sex differences in lifespan are widespread yet inconsistent across the animal kingdom. In mammals, XX females outlive XY males in over 60% of species, while this pattern reverses in birds, where ZZ males have a higher life expectancy.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inNot stated
Who it was tested in
Not stated
Kind of research
Early results, not yet checked by other scientists

The science

Original title
Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species
Authors
Randolph, E. C., Fang, Y., Meisel, R. et al.
Journal
bioRxiv (preprint, not yet peer reviewed)
Published
Oct 22, 2026
Study type
Preprint

Abstract

Sex differences in lifespan are widespread yet inconsistent across the animal kingdom. In mammals, XX females outlive XY males in over 60% of species, while this pattern reverses in birds, where ZZ males have a higher life expectancy. These sex differences raise the question of whether sex-biased aging biomarkers (age-associated molecular signatures that reflect biological aging processes) can be identified based on transcriptomic data and whether such markers are shared across taxa. To identify sex-biased aging biomarkers, we analyzed sex-specific skeletal muscle transcriptomes (RNA-seq) from young and old individuals of six species spanning major evolutionary lineages. Four female-biased and 18 male-biased aging biomarkers were identified across all species. Three shared aging biomarkers were also identified in both sexes of all species: Na Channel, Heat Shock Protein 70 (HSP70), and Secreted Protein Acidic and Rich in Cysteine (SPARC). Particularly, age-associated changes in the HSP70 family are suggestive of a shared decline in proteostasis, a hallmark of aging observed across both model and non-model organisms. Furthermore, using an Ornstein-Uhlenbeck (OU) model applied to orthogroup phylogenies, we identified lineage- and sex-dependent expression shifts in shared aging biomarkers. In addition, sex-biased orthogroups revealed age-associated alterations in muscle structure and function in females, whereas mitochondrial and metabolic pathways were predominantly changed in males, indicating divergent mechanisms in muscle aging between sexes. Together, these findings identified a set of transcriptional aging signatures, both shared and sex-biased, that are detectable across diverse evolutionary lineages, providing insight into shared and divergent molecular mechanisms underlying aging.

Read it on bioRxiv ↗

Randolph, E. C., Fang, Y., Meisel, R. et al. Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species. bioRxiv. 2026. doi:10.64898/2026.10.16.759636. https://doi.org/10.64898/2026.10.16.759636

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