Androgens as the “old age stick” in skeletal muscle

Abstract Aging is associated with a reduction in skeletal muscle fiber size and number, leading to a decline in physical function and structural integrity—a condition known as sarcopenia. This syndrome is further characterized by elevated levels of inflammatory mediators that promote skeletal muscle...

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Main Authors: Giulia Gentile, Ferdinando De Stefano, Carmela Sorrentino, Rosa D’Angiolo, Carmine Lauretta, Pia Giovannelli, Antimo Migliaccio, Gabriella Castoria, Marzia Di Donato
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Cell Communication and Signaling
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Online Access:https://doi.org/10.1186/s12964-025-02163-6
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author Giulia Gentile
Ferdinando De Stefano
Carmela Sorrentino
Rosa D’Angiolo
Carmine Lauretta
Pia Giovannelli
Antimo Migliaccio
Gabriella Castoria
Marzia Di Donato
author_facet Giulia Gentile
Ferdinando De Stefano
Carmela Sorrentino
Rosa D’Angiolo
Carmine Lauretta
Pia Giovannelli
Antimo Migliaccio
Gabriella Castoria
Marzia Di Donato
author_sort Giulia Gentile
collection DOAJ
description Abstract Aging is associated with a reduction in skeletal muscle fiber size and number, leading to a decline in physical function and structural integrity—a condition known as sarcopenia. This syndrome is further characterized by elevated levels of inflammatory mediators that promote skeletal muscle catabolism and reduce anabolic signaling. Androgens are involved in various biological processes, including the maintenance, homeostasis and trophism of skeletal muscle mass. The decline in androgen levels contributes, indeed, to androgen deficiency in aging people. Such clinical syndrome exacerbates the muscle loss and fosters sarcopenia progression. Nevertheless, the mechanism(s) by which the reduction in androgen levels influences sarcopenia risk and progression remains debated and the therapeutic benefits of androgen-based interventions are still unclear. Given the significant societal and economic impacts of sarcopenia, investigating the androgen/androgen receptor axis in skeletal muscle function is essential to enhance treatment efficacy and reduce healthcare costs. This review summarizes current knowledge on the role of male hormones and their-dependent signaling pathways in sarcopenia. We also highlight the cellular and molecular features of this condition and discuss the mechanisms by which androgens preserve the muscle homeostasis. The pros and cons of clinical strategies and emerging therapies aimed at mitigating muscle degeneration and aging-related decline are also presented.
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spelling doaj-art-d394e498e2cc41269bf63fe3ac796ee72025-08-20T03:48:02ZengBMCCell Communication and Signaling1478-811X2025-04-0123111510.1186/s12964-025-02163-6Androgens as the “old age stick” in skeletal muscleGiulia Gentile0Ferdinando De Stefano1Carmela Sorrentino2Rosa D’Angiolo3Carmine Lauretta4Pia Giovannelli5Antimo Migliaccio6Gabriella Castoria7Marzia Di Donato8Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Department of Precision Medicine, University of Campania “Luigi Vanvitelli”Abstract Aging is associated with a reduction in skeletal muscle fiber size and number, leading to a decline in physical function and structural integrity—a condition known as sarcopenia. This syndrome is further characterized by elevated levels of inflammatory mediators that promote skeletal muscle catabolism and reduce anabolic signaling. Androgens are involved in various biological processes, including the maintenance, homeostasis and trophism of skeletal muscle mass. The decline in androgen levels contributes, indeed, to androgen deficiency in aging people. Such clinical syndrome exacerbates the muscle loss and fosters sarcopenia progression. Nevertheless, the mechanism(s) by which the reduction in androgen levels influences sarcopenia risk and progression remains debated and the therapeutic benefits of androgen-based interventions are still unclear. Given the significant societal and economic impacts of sarcopenia, investigating the androgen/androgen receptor axis in skeletal muscle function is essential to enhance treatment efficacy and reduce healthcare costs. This review summarizes current knowledge on the role of male hormones and their-dependent signaling pathways in sarcopenia. We also highlight the cellular and molecular features of this condition and discuss the mechanisms by which androgens preserve the muscle homeostasis. The pros and cons of clinical strategies and emerging therapies aimed at mitigating muscle degeneration and aging-related decline are also presented.https://doi.org/10.1186/s12964-025-02163-6AndrogensAndrogen receptorAgingSarcopenia
spellingShingle Giulia Gentile
Ferdinando De Stefano
Carmela Sorrentino
Rosa D’Angiolo
Carmine Lauretta
Pia Giovannelli
Antimo Migliaccio
Gabriella Castoria
Marzia Di Donato
Androgens as the “old age stick” in skeletal muscle
Cell Communication and Signaling
Androgens
Androgen receptor
Aging
Sarcopenia
title Androgens as the “old age stick” in skeletal muscle
title_full Androgens as the “old age stick” in skeletal muscle
title_fullStr Androgens as the “old age stick” in skeletal muscle
title_full_unstemmed Androgens as the “old age stick” in skeletal muscle
title_short Androgens as the “old age stick” in skeletal muscle
title_sort androgens as the old age stick in skeletal muscle
topic Androgens
Androgen receptor
Aging
Sarcopenia
url https://doi.org/10.1186/s12964-025-02163-6
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