Mitochondria-Targeted Nutraceuticals as Metabolic Adjuncts to Physical Rehabilitation in Older Adults with Sarcopenia or Frailty: A Narrative Review

Abstract

Age-related skeletal muscle wasting, clinically expressed as sarcopenia and frailty, significantly limits the efficacy of physical rehabilitation due to an underlying cellular bioenergetic decline, mitochondrial dysfunction, and chronic inflammaging. This narrative review synthesizes current physiological and clinical evidence evaluating mitochondria- targeted nutraceuticals as targeted metabolic adjuvants to physical exercise in older adults. Comprehensive literature searches were executed across PubMed, Web of Science, and Scopus following SANRA guidelines and the SPIDER framework to evaluate functional and bioenergetic outcomes in geriatric cohorts. The findings demonstrate that target-specific biofactors directly impact mitochondrial restrictions: ubiquinol and NAD+ precursors restore electron transport chain efficiency and biogenesis; urolithin A upregulates mitophagy to prevent the cytosolic extrusion of pro-inflammatory mitochondrial DNA, while creatine monohydrate and omega-3 polyunsaturated fatty acids selectively restore downstream myofibrillar anabolic pathways. When translated to specialized clinical settings, including post-fracture orthopedic immobilization, chronic pain syndromes managed, and post-ICU-acquired weakness, these bioenergetic substrates safely mitigate tissue proteolysis and enhance recovery kinetics. In conclusion, structurally integrating biomarker-driven nutritional rehabilitation pathways with tailored exercise protocols provides the precise pro-anabolic microenvironment necessary to overcome anabolic resistance, ultimately shortening recovery timelines and maximizing functional independence in the aging population.