“Sarcopenia, affecting over 60% of individuals above age 80, represents a critical challenge for aging populations worldwide.”
BUFFALO, NY — July 13, 2026 — A new review was published in Volume 18 of Aging on June 26, 2026, titled “Hormonal dimorphism in sarcopenia disease.”
The review was led by first author Romain Menard and corresponding author Romain Madelaine from the MDI Biological Laboratory, Kathryn W. Davis Center for Regenerative Biology and Aging, Bar Harbor, Maine, USA.
Sarcopenia—the progressive loss of skeletal muscle mass, strength, and physical function with aging—is one of the leading causes of frailty and disability in older adults. Although the condition affects millions of people worldwide and has been recognized as a disease by the World Health Organization since 2016, treatment options remain largely limited to exercise and nutritional interventions, with no approved medications specifically targeting the disease. Growing evidence now suggests that one reason for this limited success is that sarcopenia develops through distinct biological mechanisms in women and men.
In this comprehensive review, the authors examine how biological sex influences the hormonal mechanisms underlying muscle aging. They focus on three peptide hormones—apelin, insulin, and oxytocin—and describe how age-related changes in these interconnected signaling networks contribute to muscle decline through distinct biological pathways in women and men.
According to the review, women often experience an abrupt decline in muscle health during menopause as estrogen levels fall rapidly. This hormonal transition disrupts apelin signaling, accelerates insulin resistance, reduces oxytocin-mediated muscle regeneration, and impairs the function of satellite cells, the muscle stem cells responsible for repair and regeneration. In contrast, men generally undergo a slower, more gradual decline in muscle function that parallels progressive reductions in testosterone, resulting in different patterns of hormonal dysregulation and disease progression.
The review also highlights the central roles of apelin, insulin, and oxytocin in maintaining healthy skeletal muscle. Together, these hormones regulate muscle metabolism, glucose utilization, mitochondrial function, protein homeostasis, inflammation, and satellite-cell activity through overlapping signaling pathways. Disruption of this hormonal network during aging is proposed to contribute to impaired muscle repair, reduced metabolic function, chronic inflammation, and progressive muscle loss.
Importantly, the authors argue that these biological differences have significant implications for diagnosis. Current biomarkers used to assess sarcopenia may not perform equally well in both sexes. For example, the review discusses evidence suggesting that apelin may serve as a particularly informative biomarker in women, whereas myostatin appears to have greater diagnostic value in men. The authors also emphasize that future biomarker development should incorporate sex-specific reference ranges rather than applying uniform diagnostic criteria to all patients.
Beyond diagnosis, the review suggests that sex differences should play a greater role in treatment development. Because hormonal regulation differs substantially between women and men, therapies targeting peptide hormones, hormone receptors, or related signaling pathways may require sex-specific approaches to maximize effectiveness. The authors also note that many existing clinical studies have not reported results separately for women and men, limiting understanding of how treatments perform across different patient populations.
The review also examines findings from a wide range of experimental models, including invertebrates, zebrafish, African turquoise killifish, rodents, and human cell systems. Together, these models provide valuable insight into the molecular pathways that drive muscle aging and offer opportunities to develop more personalized interventions tailored to the distinct biological mechanisms operating in each sex.
“Effective sarcopenia management requires a deeper understanding of peptide-hormone deregulation and development of biologically informed therapeutic strategies that acknowledge distinct disease mechanisms in men and women.”
According to the authors, future research should prioritize sex-stratified clinical studies, improved biomarker development, and therapies that account for the distinct hormonal networks regulating muscle aging in women and men. Such approaches could help move sarcopenia treatment beyond the current one-size-fits-all model toward more personalized and biologically informed care.
Overall, this review highlights that sarcopenia is not simply a uniform consequence of aging but a biologically diverse disease shaped by sex-specific hormonal regulation. By identifying how apelin, insulin, and oxytocin interact with sex hormones throughout aging, the authors provide a new framework for developing more precise diagnostic tools and personalized therapeutic strategies that may improve muscle health and healthy aging.
Paper DOI: https://doi.org/10.18632/aging.206392
Corresponding author: Romain Madelaine – [email protected]
Keywords: sarcopenia, hormonal dimorphism, muscle aging, sex-stratified medicine, sexual dimorphism
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit www.Aging-US.com and connect with us on social media:
- Bluesky
- ResearchGate
- X
- YouTube
- Spotify, and available wherever you listen to podcasts
Click here to subscribe to Aging publication updates.
For media inquiries, please contact [email protected].