Accumulation of senescent cells with age is one of the causes of aging. In recent years, the broader scientific community has become convinced of this point, and thus funding is now directed towards many varied investigations of cellular senescence and what to do about it. A young industry has emerged, made up of biotech companies focused on the selective destruction of senescent cells, mostly using small molecule drugs. Since these drugs operate through different mechanisms, tend to be tissue specific, only clear a fraction of senescent cells that varies by tissue, and will thus probably be more effective when combined together, research continues to find ever more senolytic compounds.

Senescent cells are created constantly, either in response to damage or a toxic local environment, or more commonly as the result of a somatic cell reaching the Hayflick limit on cell replication. Senescence is an irreversible state in which cell replication shuts down, and a potent mix of inflammatory signals is secreted. This can be useful in the short term, such as during wound healing, or to put a halt to potentially cancerous cells. Near all senescent cells either self-destruct or are destroyed by the immune system quite quickly. It is the tiny minority to linger that contribute to the aging process, such as by generating an environment of chronic inflammation.

The open access paper here is representative of numerous projects presently underway in the research and development communities, performing screening of small molecules from established databases in search of new senolytics. Some of these searches are more informed by prior investigation of plausible mechanisms than others, but at the end of the day the output is compounds that are then evaluated in detail for their ability to selectively destroy senescent cells. The best of the compounds noted here, fenofibrate, is on a par with navitoclax for selectivity, which is about at the lower level of what might be tolerable as a human therapy. The more off-target cells that are destroyed, the worse the side-effects. This is a starting point, however: other compounds in this category will no doubt be better, or might be engineered to be better.

Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy