Evidence of a Senescent Cell Population for which Elimination Might be Problematic – Innovita Research

Evidence of a Senescent Cell Population for which Elimination Might be Problematic

Senescent cells accumulate throughout the body with age. They are constantly created and destroyed throughout life, but the balance between creation and destruction is upset with age, leading to an accumulated burden of cellular senescence.

These cells secrete a potent mix of signals that produce chronic inflammation, disrupt tissue structure and cell function, and encourage other cells to also become senescent. The more senescent cells, the worse the impact. They are an important contributing cause of aging.

Targeted removal of senescent cells has been shown to meaningfully reverse the progression of age-related disease for numerous conditions in animal studies. Further, it extends life span in mice. These results are generally easily replicated and quite robust; we should take it as well settled that clearance of senescent cells in mammals produces literal rejuvenation.

Even so, some researchers have suggested that senescence in old tissues might be in some way adaptive, preserving cells that would otherwise not be replaced. Perhaps the balance of negative impacts favors their retention rather than destruction, even though these cells cause harm in their senescent state. This argument has been put forward for senescent T cells of the adaptive immune system, for example, given that new T cells are barely created at all in late life, and even though there are plenty of concrete examples of senescent T cells causing harm.

The proposition of cellular senescence being, on balance, better than the alternative of losing the cells in question entirely cannot be universally (or even broadly) true throughout the body, given the existing animal data on clearance, but perhaps it is true for smaller populations of senescent cells in specific tissues. In the paper I'll point out today, researchers suggest that a class of liver endothelial cells are one such population.

This must still be balanced with the greater weight of research suggesting that global clearance of senescent cells is unambiguously beneficial, but as noted here, there are questions as to just how global that global clearance is for various approaches. Populations that are beneficial may be skipped by one or another type of therapy, a situation that could lead to roadblocks in the development of therapies down the line. We shall see.

Link: Defined p16High Senescent Cell Types Are Indispensable for Mouse Healthspan

Source: Fight Aging!