The research community is now well and truly woken up when it comes to senescent cells and aging, after long years of ignoring this corner of the field, the paper linked below is illustrative of the sort of reviews on the subject being written nowadays. It took quite a while to achieve this awakening. Good evidence for senescent cell accumulation as a contributing cause of degenerative aging has existed for decades, and on the basis of that evidence clearance of senescent cells from old tissues was included in the SENS rejuvenation research proposals when they emerged at the turn of the century. Nonetheless, even as recently as five years ago researchers still struggled to raise the funds needed for the animal studies to prove the point. Once the first of those studies was completed, in 2011, things began to move, and now we have can observe an increasing pace of investment, development of practical therapies by numerous companies, and publication of new data on the biology of senescent cells. Life extension has been demonstrated in normal mice, and a recent studies demonstrate that removing senescent cells should help to slow or reverse the progression of specific age-related diseases and turn back numerous metrics of tissue aging. It is all very promising.

How do senescent cells cause harm? Largely through signaling, it appears, as they do not make up a large fraction of cells in any particular tissue even by the end of a natural life span. If even 1% of the cells in an aged tissue have become senescent, that is enough to cause significant issues. Senescent cells generate a mix of signal molecules that, in greater volume, can become very harmful; this is known as the senescence-associated secretory phenotype (SASP). It promotes chronic inflammation, alters the behavior of nearby cells for the worse, and can damage the structure of the extracellular matrix, among other issues. Why do we accumulate senescent cells? The phenomenon of senescence in old tissue appears to be an adaptation of an embryonic development process, now turned to cancer suppression. Indeed, much of its destructiveness makes more sense in the context of embryonic growth, where tissues must be removed or growth halted in order to correctly define organ structures. Cells become senescent at the Hayflick limit on division, or in response to damage or a toxic environment. In moderation this serves to reduce the risk of cancer by shutting down replication in the most vulnerable cells, those most likely to become cancerous. Levels of cellular damage and stress increase with aging, which will in turn increase the rate at which senescent cells arise. Further, senescent cells are largely destroyed either by the immune system or their own programmed cell death mechanisms. With advancing age, the immune system becomes ever more dysfunctional due to its own burden of damage, however, and thus less capable of removing senescent cells.

Therapeutic interventions for aging: the case of cellular senescence