Aging-induced dysfunction of adipose tissue and skeletal muscle and its link to insulin resistance

The extension of the human lifespan has increased the incidence of age-related metabolic disorders, such as type 2 diabetes and sarcopenia, which markedly impair quality of life and reduce life expectancy in older adults. Aging and insulin resistance synergistically compromise the functional integrity of the adipose and skeletal muscles. During aging, the adipose tissue exhibits impaired progenitor differentiation, chronic inflammation, fibrotic remodeling, and loss of thermogenic capacity. Skeletal muscles also exhibit changes, including satellite cell decline, mitochondrial dysfunction, defective protein turnover, and progressive sarcopenia. These changes diminish tissue plasticity and endocrine function and exacerbate insulin resistance through disrupted intracellular signaling and accumulation of metabolic burden. Notably, the deterioration of adipose and muscle tissue functions is interconnected, further exacerbating systemic metabolic dysfunction. Recent studies have contributed to elucidating the physiopathological causes and mechanisms of age-dependent cellular and molecular alterations in adipose and muscle tissues. This review summarizes the current insights into the cellular and molecular mechanisms underlying age-related alterations in adipose and muscle tissues and discusses emerging therapeutic strategies, including lifestyle interventions, pharmacological agents, approaches targeting senescent cells, and inter-organ communication that aim to preserve metabolic health in aging populations.