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Semin Thromb Hemost 2014; 40(06): 645-651
DOI: 10.1055/s-0034-1387883
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Role of Plasminogen Activator Inhibitor-1 in Senescence and Aging

Mesut Eren
1   Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
,
Amanda E. Boe
1   Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
2   Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Lurie Building, Chicago, Illinois
,
Ekaterina A. Klyachko
1   Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
2   Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Lurie Building, Chicago, Illinois
,
Douglas E. Vaughan
1   Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
2   Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Lurie Building, Chicago, Illinois
› Author Affiliations
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Publication History

Publication Date:
31 August 2014 (online)

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Abstract

The average age of the US population continues to increase. Age is the most important determinant of disease and disability in humans, but the fundamental mechanisms of aging remain largely unknown. Many age-related diseases are associated with an impaired fibrinolytic system. Elevated plasminogen activator inhibitor-1 (PAI-1) levels are reported in age-associated clinical conditions including cardiovascular diseases, type 2 diabetes, obesity and inflammation. PAI-1 levels are also elevated in animal models of aging. While the association of PAI-1 with physiological aging is well documented, it is only recently that its critical role in the regulation of aging and senescence has become evident. PAI-1 is synthesized and secreted in senescent cells and contributes directly to the development of senescence by acting downstream of p53 and upstream of insulin-like growth factor binding protein-3. Pharmacologic inhibition or genetic deficiency of PAI-1 was shown to be protective against senescence and the aging-like phenotypes in kl/kl and Nω-nitro-l-arginine methyl ester–treated wild-type mice. Further investigation into PAI-1's role in senescence and aging will likely contribute to the prevention and treatment of aging-related pathologies.

Keywords

PAI-1 - senescence - aging
 

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