Narrative review: lysosomal competence in aging skeletal muscle and limits of human evidence
This narrative review argues that severe experimental disruption of autophagy or lysosomal function can damage muscle, but direct evidence that lysosomal acidification, degradation or completed autophagic flux is impaired in aging human muscle remains limited. [1]
Automatic summary · not editorially reviewed
The key findings
Altered autophagy-lysosome competence has been proposed as a mechanism linking impaired proteostasis, mitochondrial damage, inflammation and regenerative failure to sarcopenia. [1]
Severe disruption of autophagy or specific lysosomal functions can cause myofiber damage, mitochondrial impairment, defective regeneration and weakness in genetic and pharmacological studies. [1]
Recent trials of metformin and once-weekly sirolimus did not improve prespecified functional outcomes in the tested populations and regimens. [1]
The source at a glance
- Study type / format
- Narrative review (abstract)
- Population / context
- Aging skeletal muscle and clinically defined sarcopenia, with evidence drawn from experimental models and human studies.
- Summary based on
- Study abstract
- Original publication
- September 28, 2026
Aging muscle, sarcopenia and proposed lysosomal mechanism
The review starts from age-related muscle deterioration, which it links to loss of mobility, frailty and disability. It notes that altered autophagy-lysosome competence has been proposed as a mechanism connecting impaired protein balance, mitochondrial damage, inflammation and failed regeneration to sarcopenia. It stresses that chronological muscle aging and clinically defined sarcopenia overlap, but evidence from healthy aging, frailty, disuse, cachexia, obesity or chronic disease cannot be treated as interchangeable.
Supporting source [1]
Experimental causal findings versus static human markers
Genetic and pharmacological studies show that severe disruption of autophagy or specific lysosomal functions can cause myofiber damage, mitochondrial impairment, defective regeneration and weakness. The review separates this causal experimental evidence from human associations. It reports that much of the human literature relies on static abundance of LC3-II, SQSTM1/p62, lysosomal proteins or transcriptional signatures, which cannot distinguish increased autophagosome formation from impaired degradation. It focuses on V-ATPase, TMEM175, LAMP proteins, TFEB/TFE3, lysophagy and crosstalk with mitophagy and the ubiquitin-proteasome system.
Supporting source [1]
Exercise and drug trials: functional outcomes not explained by flux
Exercise improves clinically relevant outcomes in older adults, but the review states that mediation through completed autophagic flux has not been established. Recent trials of metformin and once-weekly sirolimus did not improve prespecified functional outcomes in the tested populations and regimens. Urolithin A produced endpoint-specific signals while missing key primary outcomes. These are reported trial results, not evidence that lysosomal flux explains the outcomes.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a narrative review, not a new study. Direct evidence that lysosomal acidification, fusion, hydrolase activity, membrane integrity, recycling, cargo degradation or completed autophagic flux is impaired in aging human muscle remains limited, and static human markers cannot separate formation from degradation.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Dogsom O, Kim JG, Lee YH, Jahr H, Lee SS. · europepmc.org · September 28, 2026