Mesenchymal stem cells in sarcopenia: linking immune dysregulation, metabolism, and muscle regeneration

Sarcopenia, an age-related skeletal muscle disorder, is characterized by progressive loss of muscle mass, strength, and function. Exercise and nutritional interventions are integral to management, but mechanism-based therapies are limited. Chronic low-grade inflammation and remodeling of the immune microenvironment may impair muscle maintenance and regeneration. We synthesize findings on immune dysregulation in sarcopenia, focusing on macrophage interactions with muscle stem cells and fibro-adipogenic progenitors. We also examine alterations in T cells, neutrophils, B cells, and natural killer cells from the perspective of aging. We link DNA damage-related inflammation, epigenetic alterations, and metabolic disturbances within an immune–metabolic–regenerative framework. We also assess mesenchymal stem cell (MSC)-mediated regulation through paracrine signaling, extracellular vesicles, cell–cell contact, and mitochondrial transfer. Since much of this evidence derives from inflammation or injury models and immune-cell studies, its linkage to primary sarcopenia remains incompletely validated. MSCs and MSC-derived extracellular vesicles represent promising but investigational approaches for targeting the aged muscle immune–metabolic niche. By distinguishing mechanisms supported by sarcopenia or aged-muscle evidence from those that remain extrapolative or hypothesis-generating, this review provides an evidence-stratified framework to guide future mechanistic studies and therapeutic development.