Molecular mechanisms of skeletal muscle atrophy: clinical challenges and future therapeutic strategies.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing molecular mechanisms without systematic search or original human data.
PubMed 41865897 · doi:10.1016/j.bcp.2026.117913
What was done
This paper is a narrative review summarizing the molecular and cellular mechanisms underlying skeletal muscle atrophy across aging, chronic disease, and disuse. It describes key proteolytic systems, anabolic and catabolic signaling networks, translational barriers from preclinical models to humans, and potential therapeutic strategies.
What was found
The abstract provides no quantitative data or effect sizes. It details the interplay between anabolic pathways (IGF-1/PI3K/Akt/mTOR) and catabolic pathways (FOXO, myostatin/Smad, NF-κB, JAK/STAT) driving proteolytic degradation (ubiquitin-proteasome, autophagy-lysosome, calpains/caspases). It highlights emerging contributors including mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, epigenetic modifications, and non-apoptotic cell death (ferroptosis, pyroptosis), while noting the exploratory status of stem cell, exosome, and precision interventions.
Why it matters
It provides a comprehensive conceptual framework of muscle wasting pathways to guide translational research and identify multivalent therapeutic targets.
Limits
The review presents mechanistic models and expert synthesis rather than primary empirical data. No systematic search strategy, quantitative meta-analysis, or specific human trial outcomes are reported in the abstract.
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