Aged human muscle secretes an enzyme that impairs stem cell maintenance
Profiling conditioned media revealed that altered sphingolipid signaling reduces muscle stem cell pools in human cell cultures.
bioRxiv · Crisol B et al. · Paper published 2 Oct 2026
In cell culture experiments using primary muscle cells from young (15–25 years) and aged (60–86 years) human donors, researchers evaluated how aging alters the muscle secretome. Proteomic profiling of conditioned media identified 127 age-dependent secreted proteins. The lysosomal enzyme acid sphingomyelinase (ASM), which converts sphingomyelin into ceramide, was the most upregulated secreted factor with age. Adding recombinant ASM to young cultures reduced PAX7+ muscle stem cells, demonstrating that extracellular ASM impairs stem cell maintenance. Lipidomic profiling revealed a disrupted sphingomyelin-ceramide-S1P axis, with reduced levels of sphingomyelin and S1P. Supplying exogenous S1P restored the muscle stem cell pool in aged cultures.
Why it matters
These findings directly link age-related secretome remodeling and disrupted sphingolipid metabolism to the decline of muscle stem cells. They highlight ASM and S1P as potential metabolic targets to protect stem cell maintenance.
Caveats
This study is a preprint and has not yet been peer-reviewed. The findings are based solely on in vitro human cell cultures rather than intact tissues or living organisms.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Aging remodels the human muscle secretome, impairing stem cell via sphingolipid metabolism
Crisol B, Pinzon N, Bensalah M et al.
bioRxiv · 2 Oct 2026 · Preprint, not yet peer-reviewed
- Relevance
- Core geroscience
- News value
- Notable
- Evidence
- Cells
- Status
- Preprint
Latest stories
Gastrodia elata polysaccharide extends worm lifespan and mitigates age-related deficits in mice
The treatment reduced oxidative stress, suppressed inflammation, and remodeled the gut microbiome in naturally aging mice while prolonging survival in nematodes.
Food science & nutrition · Shi H et al.
Simulated microgravity increases transcriptomic age in human organoids
Culturing human neural, cardiac, and tonsil models in rotating-wall vessels for 24 hours also shifted contraction dynamics and immune gene expression.
bioRxiv · Mu W-C et al.
Rank normalization resolves distinct proteome degradation pathways in cultured cells
A percentile-based normalization method reveals substrate preferences between proteasomal and lysosomal clearance systems in cultured cells.
bioRxiv · Gao Z et al.
Melissic acid reduces senescence in human stem cells via cAMP signaling
A screen of 800 natural compounds identified a phytochemical that activates autophagy and restores cell-cycle activity in models of cellular exhaustion.
Frontiers in pharmacology · Yang K et al.