Intervening to Prevent Consequences of Cellular Senescence

Senescent cells are those that have removed themselves from the cell cycle in response to damage or a tissue signaling environment that reflects nearby damage. This is an adaptation that serves to reduce cancer risk, at least in the early stages of aging, but it also causes harm as senescent cells accumulate in larger numbers. These cells emit signal molecules that degrade surrounding tissue structures, harm tissue function, and increase the odds of nearby cells also becoming senescent. Thus the accumulation of senescent cells over the years is one of the contributing causes of degenerative aging.

The ideal and simplest approach to removing this issue is to adapt targeted cell killing technologies under development in the cancer research community to periodically clear out senescent cells in the body. Other more complicated paths may be an option, however, such as reprogramming cells to reverse senescence, or as in this case blocking some of the signal molecules released by senescent cells, making them much less harmful to surrounding tissues:

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 [mice]. Further investigation into PAI-1's role in senescence and aging will likely contribute to the prevention and treatment of aging-related pathologies.