A Popular Science Article on Senescent Cells and Efforts to Clear them from the Aging Body

Senescent cells are constantly created and destroyed in the body, but begin to linger with advancing age. The secretions produced by senescent cells are useful in the short term, but increasingly harmful when maintained over the long term, inflammatory and disruptive of tissue structure and function. The production of senolytic drugs to clear senescent cells from aged tissues is an established area of research and clinical development, but is proceeding just as slowly as these matters usually do. The early senolytic combination of dasatinib and quercetin appears quite good, but will not be further developed by industry because these are cheap, off-patent compounds. There is much that could be done by philanthropists to speed up clinical trials, proof of efficacy, and widespread adoption. It is a little ridiculous that the first rejuvenation therapy worthy of the name exists, but very few groups are attempting to advance its adoption.

The emergence of senescent cells in aging people isn't necessarily a problem in and of itself. The problem seems to be that they hang around for too long. Researchers suspect this happens because the immune system in aging individuals isn't up to the task of eliminating them all. And when senescent cells stay put, the cocktail of molecules they produce, and the ongoing immune response, can damage surrounding tissues. Senescence can also contribute to cancer, but the relationship is multifaceted. Senescence itself is a great defense against cancer - cells that don't divide don't form tumors. On the other hand, the molecules senescent cells emit can create an inflamed, cancer-promoting environment

Researchers went hunting for senolytic drugs that would kill senescent cells while leaving their healthy neighbors untouched. They reasoned that since senescent cells appear to be resistant to a process called apoptosis, or programmed cell death, medicines that unblock that process might have senolytic properties. Some cancer drugs do this, and the researchers included several of these in a screen of 46 compounds they tested on senescent cells grown in lab dishes. The study turned up two major winners: One was the cancer drug dasatinib, an inhibitor of several natural enzymes that appears to make it possible for the senescent cells to self-destruct. The other was quercetin, a natural antioxidant that's responsible for the bitter flavor of apple peels and that also inhibits several cellular enzymes. Each drug worked best on senescent cells from different tissues, the scientists found, so they decided to use them both, in a combo called D+Q, in studies with mice.

Scientists have since discovered several other medications with senolytic effects, though D+Q remains a favorite pairing. Further studies from several research groups reported that senolytics appear to protect mice against a variety of conditions of aging, including the metabolic dysfunction associated with obesity, vascular problems associated with atherosclerosis, and bone loss akin to osteoporosis. Despite the excitement, senolytic research remains in preliminary stages. A lot of basic and clinical research must happen first, but if everything goes right, senolytics might someday be part of a personalized medicine plan: The right drugs, at the right time, could help keep aging bodies healthy and nimble. It may be a long shot, but to many researchers, the possibility of nixing walkers and wheelchairs for many patients makes it one worth taking.

Link: https://www.asbmb.org/asbmb-today/science/012923/old-cells-turn-back-the-clock

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