From Fight Aging!: More Details on Bcl-2 Inhibitors as Senolytic Drugs

A few weeks ago researchers announced the discovery of a potential new class of drug capable of some degree of clearance of senescent cells in old tissues. As an approach to treating aging and its associated medical conditions this has long been advocated by the SENS Research Foundation, and is now coming to be known as a senolytic therapy. The paper is published in Nature Medicine, but is unfortunately not open access. The researchers there referred to the most effective drug candidate by its development code name, ABT-263. Another collaborating research group, those involved in identifying dasatinib and quercetin as senolytic drugs in research announced earlier this year, published their own paper on the ABT-263 discovery yesterday in Aging Cell. There they use ABT-263’s generic name navitoclax, and this latest paper is open access, so you’ll find more of the details laid out and easily accessible.

Cells become senescent as a result of damage, toxins, and stress, ceasing to divide and secreting a range of signals. This is most likely an evolutionary adaptation of processes involved in embryonic development and wound healing that have also come to suppress cancer risk in early old age, shutting down the ability to replicate in those cells most at risk. Senescent cells are destroyed by their own programmed cell death mechanisms or by the immune system, but some evade these fates and linger. The immune system becomes damaged and ineffective itself in later life, and that no doubt doesn’t help matters. As senescent cells accumulate in ever greater numbers over the years, the combined effects of their secreted signals become damaging to surrounding tissues, generating inflammation, remodeling important structures, and eventually encouraging the generation of cancer rather than suppressing it. The presence of senescent cells contributes to the progression of near all of the common age-related diseases.

Selective destruction of cells is a major theme in cancer research and other areas of medicine, and destruction of senescent cells looks to be the shortest path to removing this contribution to degenerative aging. A good means of clearing these cells means that we don’t have to stop to fully understand how and why cellular senescence causes damage – we can just test removal in the laboratory and look for a beneficial outcome. So far, that is exactly the outcome seen in animal studies. Early this year the first senolytic drug combination of dasatinib and quercetin was tested in mice with mediocre results in terms of percentage of cells cleared and a level of removal that varied widely by tissue type. Nonetheless it produced measurable, significant benefits after just a single treatment. This is a form of narrow, selective rejuvenation, the restoration of some parameters of biology in a living individual to the state they were in earlier life.

The rest of the article can be read here.

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