The Central Role of the AMPK/SIRT1/PGC-1α Signaling Axis in Skeletal Muscle Physiology and Pathology and Its Targeted Therapeutic Strategies.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing molecular mechanisms with no original clinical data or systematic search methodology reported.
PubMed 42515737 · doi:10.3390/ph19071056
What was done
The authors reviewed the structural functions, regulatory mechanisms, and synergistic interactions of the AMPK/SIRT1/PGC-1α signaling pathway in skeletal muscle. The review examined its role in physiological adaptations (such as exercise adaptation and muscle fiber-type transformation) and pathological conditions (including sarcopenia, disuse atrophy, cachexia, neurogenic atrophy, muscular dystrophy, and type 2 diabetes mellitus-related myopathy). It also surveyed therapeutic approaches (exercise, nutritional/natural products, small molecules, and gene/cell therapies) targeting this axis.
What was found
The abstract reports no numerical data or quantitative outcomes. It presents a mechanistic synthesis describing the AMPK/SIRT1/PGC-1α axis as an energy-sensing signaling hub that coordinates mitochondrial biogenesis, muscle fiber switching, and protein homeostasis, while outlining translational challenges such as signaling network complexity, individual variability, and bioavailability.
Why it matters
This review integrates molecular pathways governing skeletal muscle metabolic homeostasis and plasticity, providing a conceptual framework for therapeutic development across various muscle-wasting conditions and metabolic diseases.
Limits
The abstract describes a narrative review with no systematic search criteria, meta-analytic pooling, or primary clinical trial data. No sample sizes, effect sizes, or quantitative safety and efficacy metrics for the proposed interventions are reported.
Cited by
- supports Exercise, cold therapy, sauna, niacin (vitamin B3), and a low-carbohydrate diet increase mitochondrial biogenesis, whereas refined sugars and starches destroy mitochondria.