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. Author manuscript; available in PMC: 2021 Feb 14.
Published in final edited form as: Circ Res. 2020 Feb 13;126(4):533–551. doi: 10.1161/CIRCRESAHA.119.315889

Figure 2. Schematic of Secreted Factors Contributing to Age-related Cardiac Disease.

Figure 2.

Accumulating senescent cells adversely affect other cells (e.g. cardiomyocytes and fibroblasts) through a senescence-associated secretory phenotype (SASP) which promotes inflammation, cell death and senescence. While systemic increases in senescent cells lead to increasing secretion of typical SASP proteins with age (e.g., IL-1α, IL-1β, IL-6, Cxcl1), senescent cardiomyocytes secrete non-typical SASP (e.g., GDF15, Tgfb2, and Edn3). Circulating activin and ANGPTL2 are also increased with age. Elevated activin, through binding to its receptor ActRIIb, triggers Smurf1-mediated ubiquitination and subsequent degradation of SERCA2a, while increased ANGPTL2 inactives Akt and thereby degrades SERCA2a. All of these processes contribute to cardiac aging and cardiac dysfunction.