Senescence-Associated Secretory Phenotype (SASP) in Diabetes

Review Article

Abstract

Cellular senescence represents a critical biological process characterized by permanent cell cycle arrest and distinct metabolic alterations. The senescence-associated secretory phenotype (SASP) has emerged as a fundamental mediator linking cellular aging to various pathological conditions, including diabetes mellitus. Recent investigations have unveiled the intricate relationship between SASP and pancreatic β-cell dysfunction, insulin resistance, and diabetic complications. The accumulation of senescent cells in pancreatic islets correlates with diminished insulin production and secretion, while SASP factors contribute to chronic inflammation and oxidative stress. The molecular mechanisms underlying SASP in diabetes involve complex interactions between p16INK4a/p53 pathways, DNA damage responses, and inflammatory mediators. Notably, senescent β-cells exhibit altered expression of key metabolic regulators and increased production of pro-inflammatory cytokines, chemokines, and matrix-degrading proteins. The identification of these pathways has led to innovative therapeutic strategies, including senolytic drugs that selectively eliminate senescent cells. Preclinical studies demonstrate that targeting SASP can improve glucose homeostasis, enhance insulin sensitivity, and potentially reverse diabetic complications. Moreover, the interaction between SASP and metabolic dysfunction extends beyond pancreatic tissue, affecting adipose tissue, skeletal muscle, and liver function