Aging remodels the human muscle secretome, impairing stem cell via sphingolipid metabolism
- 1Sorbonne Universite, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France
Abstract
Aging reduces skeletal muscle regenerative capacity, but how the aged environment impairs muscle stem cells (MuSCs) remains unclear. Skeletal muscle acts as a secretory organ, yet age-related changes in its secretome and impact on stem cells are poorly understood. We performed proteomic and lipidomic analyses of conditioned media from primary muscle cells of young (15-25 years) and aged (60-86 years) donors. We identified 127 age-dependent secreted proteins, revealing major remodeling. The lysosomal enzyme acid sphingomyelinase (ASM), which converts sphingomyelin into ceramide, was the most upregulated factor. Recombinant ASM reduced PAX7+ MuSCs in young cultures, showing extracellular ASM impairs stem cell maintenance. Lipidomics revealed disruption of the sphingomyelin-ceramide-S1P axis, with decreased sphingomyelin and S1P, a lipid promoting MuSC proliferation. Exogenous S1P restored the stem cell pool in aged cultures. These findings link secretome remodeling and sphingolipid metabolism to MuSC decline and identify ASM and S1P as targets
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BibTeX
@misc{crisol2026aging,
title = {{Aging remodels the human muscle secretome, impairing stem cell via sphingolipid metabolism}},
author = {B. Crisol and N. Pinzon and M. Bensalah and J. Ohana and M. Lhomme and M. Ponnaiah and J. Bruce and M. Kondili and L. Gaut and E. Negroni and A. Boulinguiez and G. S. Butler-Bowne and V. Mouly and C. Trollet and A. Bigot},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.755640},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.755640v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Aging remodels the human muscle secretome, impairing stem cell via sphingolipid metabolism
AU - B. Crisol
AU - N. Pinzon
AU - M. Bensalah
AU - J. Ohana
AU - M. Lhomme
AU - M. Ponnaiah
AU - J. Bruce
AU - M. Kondili
AU - L. Gaut
AU - E. Negroni
AU - A. Boulinguiez
AU - G. S. Butler-Bowne
AU - V. Mouly
AU - C. Trollet
AU - A. Bigot
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.755640
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.755640v1
AB - Aging reduces skeletal muscle regenerative capacity, but how the aged environment impairs muscle stem cells (MuSCs) remains unclear. Skeletal muscle acts as a secretory organ, yet age-related changes in its secretome and impact on stem cells are poorly understood. We performed proteomic and lipidomic analyses of conditioned media from primary muscle cells of young (15-25 years) and aged (60-86 years) donors. We identified 127 age-dependent secreted proteins, revealing major remodeling. The lysosomal enzyme acid sphingomyelinase (ASM), which converts sphingomyelin into ceramide, was the most upregulated factor. Recombinant ASM reduced PAX7+ MuSCs in young cultures, showing extracellular ASM impairs stem cell maintenance. Lipidomics revealed disruption of the sphingomyelin-ceramide-S1P axis, with decreased sphingomyelin and S1P, a lipid promoting MuSC proliferation. Exogenous S1P restored the stem cell pool in aged cultures. These findings link secretome remodeling and sphingolipid metabolism to MuSC decline and identify ASM and S1P as targets
ER -