Abstract
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.
Highlights
Cellular senescence is a stress-response mechanism inducing cell cycle arrest; cells cease to divide, but remain metabolically active and undergo distinctive phenotypic changes [1]
Senescent cells are identified using a combination of markers, which include, among others, high levels of p16 and p21, two cyclin-dependent kinase inhibitors (CDKi), detection of lysosomal hydrolase activity at pH 6, known as senescence-associated β-galactosidase (SA-βGal), identification of senescence-associated heterochromatin foci (SAHF) in the nucleus and loss of nuclear lamina protein lamin B1 (LMNB1) [8,9,10,11]
We propose that angptl2 is an understudied senescence marker with a potential—but still speculative—clinical utility as a biomarker of age-related diseases
Summary
Cellular senescence is a stress-response mechanism inducing cell cycle arrest; cells cease to divide, but remain metabolically active and undergo distinctive phenotypic changes [1]. Angptl may contribute to the pathogenesis of these chronic inflammatory and age-related diseases via its inflammatory [26], pro-fibrotic [54], pro-oxidant properties [55,56] and activation of metalloproteinases [57] (for review, see [36]). Another property of angptl, rarely mentioned in the literature, is its contribution to cellular senescence. Circulating levels of angptl are used for the prediction and prognosis of multiple age-related diseases (for review, see [36]), in which cellular senescence and SASP are key players. Whether angptl could be a therapeutic target is beyond the scope of this review
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