Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease
- 1Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong University, Nantong 226001, China
Abstract
Skeletal muscle regeneration is essential for recovery after injury and for maintaining physical and metabolic function. This capacity declines with aging and is often impaired in chronic diseases, limiting effective repair. This review summarizes the main mechanisms that regulate muscle repair, with a focus on satellite cell activity and its interaction with inflammatory, metabolic, vascular, and fibrotic signals at the molecular and cellular level. We discuss how these processes are disrupted in aging, Duchenne muscular dystrophy, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, and cancer cachexia, leading to delayed repair, reduced myogenic differentiation, and fibrosis. We also review current and emerging strategies to improve muscle regeneration, including exercise, bioactive molecules, physical stimulation, gene-based approaches, engineered biomaterials, and cell or cell-derived therapies. Across these conditions, chronic inflammation, metabolic dysfunction, and fibrotic remodeling appear to be common barriers to effective regeneration. Multi-target therapeutic approaches may offer advantages over single-pathway interventions, although clinical evidence is still limited; initial preclinical results, however, are promising.
Related
- The cellular ecosystem of skeletal muscle regeneration: molecular mechanisms, pathological disorders, and potential therapeutic strategies
- Neuromuscular Junction Degeneration in Skeletal Muscle Atrophy: Disease-Specific Mechanisms, Evidence-Informed Stratification, and Therapeutic Windows
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects
- The Glyco-Code Molecular Template Instructively Guides Skeletal and Neural Development, Tissue Regeneration and Dynamic Repair Responses Following Trauma and Disease
- Tissue composition shapes differential skeletal integration strategies during axolotl limb regeneration
BibTeX
@article{li2026mechanisms,
title = {{Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease}},
author = {Xia Li and Zihao Zhao and Jiawen Yang and Yijie Zhang and Xinlei Yao and Hualin Sun and Yuntian Shen},
journal = {Pharmaceuticals},
year = {2026},
month = jul,
doi = {10.3390/ph19071091},
url = {https://doi.org/10.3390/ph19071091},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mechanisms of Impaired Skeletal Muscle Regeneration and Therapeutic Approaches in Aging and Chronic Disease
AU - Xia Li
AU - Zihao Zhao
AU - Jiawen Yang
AU - Yijie Zhang
AU - Xinlei Yao
AU - Hualin Sun
AU - Yuntian Shen
PY - 2026
DA - 2026/07/15
JO - Pharmaceuticals
DO - 10.3390/ph19071091
UR - https://doi.org/10.3390/ph19071091
AB - Skeletal muscle regeneration is essential for recovery after injury and for maintaining physical and metabolic function. This capacity declines with aging and is often impaired in chronic diseases, limiting effective repair. This review summarizes the main mechanisms that regulate muscle repair, with a focus on satellite cell activity and its interaction with inflammatory, metabolic, vascular, and fibrotic signals at the molecular and cellular level. We discuss how these processes are disrupted in aging, Duchenne muscular dystrophy, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, and cancer cachexia, leading to delayed repair, reduced myogenic differentiation, and fibrosis. We also review current and emerging strategies to improve muscle regeneration, including exercise, bioactive molecules, physical stimulation, gene-based approaches, engineered biomaterials, and cell or cell-derived therapies. Across these conditions, chronic inflammation, metabolic dysfunction, and fibrotic remodeling appear to be common barriers to effective regeneration. Multi-target therapeutic approaches may offer advantages over single-pathway interventions, although clinical evidence is still limited; initial preclinical results, however, are promising.
SN - 1424-8247
ER -