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
