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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.

Link: http://dx.doi.org/10.1055/s-0034-1387883

Comments

A web search reveals several dietary approaches to reducing PAI-1 levels.

Some flavonoids may be effective -
"Green tea polyphenols inhibit plasminogen activator inhibitor-1 expression and secretion in endothelial cells"
http://www.ncbi.nlm.nih.gov/pubmed/19713834

Monosaturated fat may also be beneficial -
"Monounsaturated Fatty Acid–Enriched Diet Decreases Plasma Plasminogen Activator Inhibitor Type 1"
http://www.ncbi.nlm.nih.gov/pubmed/8548431

Low glycemic diets also appear to reduce PAI-1.

Posted by: Lou Pagnucco at September 5th, 2014 11:48 AM

Given that these cells seem to become senescent in response to internal or external damage, I'd guess, along with most people, that removal will be a much safer strategy than resetting these cells. I'd also speculate that it will probably be the only way to 100% reduce the damaging chemicals that these cells emit too.

Posted by: Jim at September 5th, 2014 6:54 PM

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