Plasminogen Activator Inhibitor-1 Is a Marker and a Mediator of Senescence

Abstract

Plasminogen Activator Inhibitor-1 (PAI-1) is a member of the evolutionarily conserved serine protease inhibitor (SERPIN) family, and a potent and rapid-acting inhibitor of both of the mammalian plasminogen activators. Organismal homeostasis requires physiological levels of endogenous PAI-1 and increased PAI-1 production guides the onset and progression of numerous human diseases and contributes to the multimorbidity of aging. Both chronological and stress-induced accelerated aging are associated with cellular senescence and accompanied by marked increases in PAI-1 expression in tissues. Recent studies suggest that PAI-1 is not only a marker but also a key mediator of cellular senescence and organismal aging. Here, we review the significance of PAI-1 as a bonafide marker as well as a critical mediator of cellular senescence associated with aging and aging-related pathologies.

Health benefits of resveratrol: Evidence from clinical studies

“…In stable angina pectoris cases, resveratrol reduces BNP which suggests improved ventricular function . PAI‐1 is considered to be a common factor in various clinical conditions particularly in obesity, diabetes, and CVDs; and resveratrol ameliorates pathophysiological complications by suppressing this molecular target . IGF‐1 and IGFBP‐3, the crucial regulators in cancer pathogenesis, could be inhibited by resveratrol treatment …”

Thrombotic Regulation From the Endothelial Cell Perspectives

“…It functions as the principal inhibitor of tissue-or urokinase-type plasminogen activator, and hence fibrinolysis, with additional nonfibrinolytic function recently discovered. [45][46][47] PAI-1 is mainly produced by the endothelium but is also secreted by other tissue types, such as adipose tissue. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis.…”

“…48 Transgenic mice overexpressing PAI-1 developed age-dependent coronary arterial thromobosis. Recent studies reviewed by Vaughan et al 46 suggest PAI-1 as a mediator of cellular senescence. Normalization/inhibition of elevated PAI-1 might be a new strategy to control age-associated pathologies, including thrombosis, arteriosclerosis, obesity, diabetes mellitus, among which endothelial dysfunction/senescence represents a common pathology.…”

[No] Need for Speed: Late-onset Diseases as Evolution's Power Brakes

“…It is more likely that with the achievements of modern research and clinical medicine, the life expectancy of individuals with late-onset disease that were diagnosed and treated early may become similar to the life expectancy of those that died 'of old age' . There is also significant advancement in research of genotype-phenotype correlations of aging phenotypes and late-onset disease and a number of genetic and phenotypic markers have been developed that may aid in the prognostication of age of onset and potential course of disease [9,12,13]. Thus, we may need to re-evaluate and restructure the goals of modern research and clinical care, concentrating more effort at development of treatment and management strategies that may significantly improve survival and quality of life for the patients with common late-onset diseases.…”