Han Li

Skeletal muscle aging is a conserved biological process characterized by progressive declines in muscle mass, strength, regenerative capacity, and metabolic adaptability, contributing to impaired mobility, frailty and age-related diseases. Beyond its canonical role in locomotion, skeletal muscle functions as an endocrine and metabolic organ that actively regulates organismal aging through myokines, metabolites, extracellular vesicles, thermogenic activity, and dynamic communication with distant organs. In this review, we summarize the intrinsic mechanisms driving skeletal muscle aging, including protein turnover imbalance and anabolic resistance, myosteatosis, denervation and motor unit loss, and cellular composition remodeling. We also discuss how aging skeletal muscle influences systemic aging through bidirectional interactions with metabolic organs, brain, cardiovascular system, and bone via endocrine signaling and interorgan communication. Finally, we highlight emerging interventions targeting skeletal muscle aging, including exercise, nutritional strategies, pharmacological approaches, and other novel therapies. Understanding skeletal muscle as both a target and regulator of systemic aging provides a framework for developing strategies to promote healthy aging and reduce the burden of age-associated diseases.

Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)—particularly small EVs (sEVs)—transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches—including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence—that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25–45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing.

Obesity leads to a chronic inflammatory state throughout the body, with increased infiltration of immune cells and inflammatory factors in skeletal muscle tissue, and, at the same time, the level of intracellular mitochondrial oxidative stress rises. Meanwhile, obesity is closely related to the development of skeletal muscle fibrosis and can affect the metabolic function of skeletal muscle, triggering metabolic disorders such as insulin resistance (IR) and type 2 diabetes (T2D). However, whether there is a mutual regulatory effect between the two pathological states of inflammation and fibrosis in obese skeletal muscle and the specific molecular mechanisms have not been fully clarified. This review focuses on the pathological changes of skeletal muscle inflammation and fibrosis induced by obesity, covering the metabolic changes it causes, such as lipid deposition, mitochondrial dysfunction, and dysregulation of inflammatory factors, aiming to reveal the intricate connections between the two. In terms of intervention strategies, aerobic exercise, dietary modification, and pharmacotherapy can improve skeletal muscle inflammation and fibrosis. This article provides insight into the important roles of inflammation and fibrosis in the treatment of obesity and the management of skeletal muscle diseases, aiming to provide new ideas for the diagnosis and treatment of metabolic diseases such as obesity and IR.