Review Examines How Senescent Cells May Worsen Metabolic Disease

An open-access review published September 2, 2026, examines how cellular senescence may contribute to metabolic disorders including type 2 diabetes, fatty liver disease and metabolic dysfunction-associated steatohepatitis, or MASH. The review describes a potentially self-reinforcing relationship: metabolic stress can promote cellular senescence, while senescent cells may release inflammatory signals that worsen tissue dysfunction.

Senescent cells are cells that have stopped dividing but remain metabolically active. According to the review, these cells accumulate throughout life, while the immune system’s ability to remove them declines with age. Excess visceral fat and the metabolic dysfunction associated with being overweight may accelerate that accumulation.

The researchers focus on the senescence-associated secretory phenotype, commonly abbreviated as SASP. This involves the release of cytokines, chemokines and enzymes that can influence neighboring cells and tissues. In adipose tissue, the review says, senescent precursor and mature fat cells may contribute to persistent, low-grade inflammation, impaired insulin signaling and increased exposure to damaging lipids throughout the body.

The proposed effects extend beyond fat tissue. In the liver, senescence in hepatocytes and stellate cells is described as a contributor to the progression from fat accumulation toward MASH and cirrhosis. SASP-related signals may promote fibrosis, the infiltration of immune cells and changes in cellular metabolism. In the pancreas and skeletal muscle, senescence may undermine insulin-producing beta-cell function and glucose uptake, respectively, potentially worsening insulin resistance and elevated blood glucose.

The review distinguishes this chronic accumulation of senescent cells from short-term senescence, which can have protective roles in processes such as wound healing and tumor suppression. In older or obese individuals, however, the authors describe a persistent inflammatory environment—sometimes termed “inflammaging”—as a possible contributor to obesity-related and cardiometabolic disease.

Evidence cited in the review from rodent models links reductions in senescent-cell markers with improved metabolic measures, lower fibrosis and better insulin sensitivity. Those findings indicate possible translational relevance, but they do not establish that senescent-cell-clearing treatments work for metabolic disease in humans or that they can prevent, delay or reverse its onset.

The source also notes that companies are developing senolytic drugs intended to remove some senescent cells. It says that early senolytic approaches, including a dasatinib-and-quercetin combination, are being used off-label by some people, while producing little solid evidence about effectiveness for particular uses. The review’s discussion suggests that clinical testing specifically focused on metabolic disease is not expected soon, leaving the human therapeutic significance of senescent-cell clearance unresolved.