Senescence-associated glycoprotein (SAGP)

Senescence-associated glycoprotein (SAGP) is a novel protein identified as a specific biomarker and survival factor for senescent cells. Localized primarily to the lysosome, SAGP plays a critical role in maintaining lysosomal homeostasis and protecting senescent cells from the stress associated with their metabolic state. It has been shown to bind to V-ATPase, a proton pump essential for acidifying organelles, and its deficiency leads to increased lysosomal pH, impaired mitophagy, and elevated mitochondrial reactive oxygen species. SAGP is significantly upregulated in various age-related conditions, including atherosclerosis, type 2 diabetes, and Alzheimer's disease, where it is particularly enriched in activated microglia and vascular endothelial cells. Therapeutic strategies targeting SAGP, such as senolytic vaccines, aim to selectively eliminate SAGP-positive senescent cells to reduce chronic inflammation and alleviate disease pathology. In preclinical models, vaccination against SAGP has demonstrated efficacy in reducing amyloid plaques, improving cognitive behavior, and extending lifespan.

Other names

SAGPSAGP-proteinSenescence-associated glycoprotein

Elimination of SAGP-positive senescent cells (senolysis) via vaccine-induced immune response