Fat talks first: how adipose tissue sets the pace of aging?

Once viewed primarily as an energy reservoir, adipose tissue (AT) is now recognized as a key endocrinal organ in regulating systemic aging. With age, AT undergoes significant remodeling, marked by altered fat distribution, visceral fat expansion, impaired thermogenesis, and chronic low-grade inflammation, which disrupts metabolic and immune homeostasis. Emerging insights from single-cell and spatial transcriptomics highlight the critical roles of adipose progenitors, immune cells, and senescent cells in driving local dysfunction and systemic decline. Through inflammatory and metabolic signaling, dysfunctional AT actively contributes to age-related pathologies. This review explores how AT functions as both an early sensor and driver of aging and discusses therapeutic opportunities targeting adipose dysfunction to promote healthy aging.