ANGPTL2 as a Marker of Cellular Senescence

The accumulation of senescent cells is an important contributing cause of degenerative aging. Since these cells can be specifically targeted via a range of mechanisms, and selective destruction of senescent cells produces significant and rapid rejuvenation in animal studies, there is considerable interest in the research community in finding novel ways to measure the burden of cellular senescence. Senescent cells secrete a mix of pro-growth, inflammatory molecules into circulation, and so it is possible that some of those molecules can form the basis for low-cost assays conducted on blood samples.

Cellular senescence is a cell fate primarily induced by DNA damage, characterized by irreversible growth arrest in an attempt to stop the damage. Senescence is a cellular response to a stressor and is observed with aging, but also during wound healing and in embryogenic developmental processes. Senescent cells are metabolically active and secrete a multitude of molecules gathered in the senescence-associated secretory phenotype (SASP). The SASP includes inflammatory cytokines, chemokines, growth factors, and metalloproteinases, with autocrine and paracrine activities.

Among hundreds of molecules, angiopoietin-like 2 (angptl2) is an interesting, although understudied, SASP member identified in various types of senescent cells. Angptl2 is a circulatory protein, and plasma angptl2 levels increase with age and with various chronic inflammatory diseases such as cancer, atherosclerosis, diabetes, heart failure and a multitude of age-related diseases. In this review, we will examine in which context angptl2 was identified as a SASP factor, describe the experimental evidence showing that angptl2 is a marker of senescence in vitro and in vivo, and discuss the impact of angptl2-related senescence in both physiological and pathological conditions. Future work is needed to demonstrate whether the senescence marker angptl2 is a potential clinical biomarker of age-related diseases.


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