Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species
- 1Cornell University
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.
Related
- Molecular Adaptations and Sex‐Biased Regulatory Pathways in Multi‐Year Diapause of the Cabbage Beetle Colaphellus bowringi : A Duration‐Resolved Transcriptomic Analysis
- Spectroscopic Study of the Common Features of Melanins Synthesized from a Diverse Range of Precursors
- Predicting forage yield and water use efficiency using machine learning across diverse forage species under varying irrigation and fertilizer management in the Ethiopian highlands
- Diverse signaling proteins recruit RCC1-Like Domain proteins to the plasma membrane through a common structural framework.
- Transcriptomic profiling reveals estradiol and progesterone specific microRNA signatures differentially regulate mRNA targets in vaginal epithelial cells
BibTeX
@misc{randolph2026common,
title = {{Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species}},
author = {E. C. Randolph and Y. Fang and R. Meisel and J. Walters and T. Gamble and G. Wilkinson and E. Larschan and A. Webb and IISAGE Consortium and P. Biga and N. Riddle and J. E. Duan},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.16.759636},
url = {https://www.biorxiv.org/content/10.64898/2026.10.16.759636v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Common and Sex-Biased Muscle Transcriptomic Aging Signatures Across Diverse Species
AU - E. C. Randolph
AU - Y. Fang
AU - R. Meisel
AU - J. Walters
AU - T. Gamble
AU - G. Wilkinson
AU - E. Larschan
AU - A. Webb
AU - IISAGE Consortium
AU - P. Biga
AU - N. Riddle
AU - J. E. Duan
PY - 2026
DA - 2026/10/16
PB - bioRxiv
DO - 10.64898/2026.10.16.759636
UR - https://www.biorxiv.org/content/10.64898/2026.10.16.759636v1
AB - 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.
ER -