Cellular Senescence in Blood Cells: A Link Between Metabolic Syndrome, Inflammaging and Cardiometabolic Disease

Metabolic syndrome (MetS) is a complex metabolic disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which contribute to an increased risk of type 2 diabetes mellitus, cardiovascular disease, and premature mortality. Emerging evidence suggests that cellular senescence plays a central role in the pathophysiology of MetS by linking metabolic stress to chronic inflammation, immune dysfunction, as well as cell and tissue damage. Although senescence has traditionally been studied in tissue-resident cells, growing attention has focused on the role of blood-cell senescence in the initiation and progression of metabolic disease. This review summarizes current knowledge regarding the molecular and cellular mechanisms driving senescence in hematopoietic stem cells and circulating blood-cells (BCs) and how these mechanisms affect specific blood-cell populations leading to altered immune function, impaired tissue homeostasis, and persistent inflammatory activation. The link between clonal hematopoiesis to immunosenescence and cardiometabolic disease is also highlighted, providing additional insight into the complex interactions between hematopoietic aging and metabolic dysfunction.