Aubrey de Grey on Progress Towards Rejuvenation Therapies Targeting Cellular Senescence

There are at present many programs of medical research and development focused on senescent cells: selectively destroying them, suppressing their inflammatory secretions, or preventing cells from becoming senescent in the first place. The accumulation of senescent cells is an important contribution to degenerative aging, and senolytic treatments that clear a sizable fraction of such cells produce a noteworthy degree of rejuvenation in mice. The first human trials are underway, and soon enough the world will wake to the fact that much of the inflammatory dysfunction of aging can be eliminated by existing, cheap drugs such as the dasatinib and quercetin combination.

With investment money flowing freely into start-ups developing senotherapeutics, and companies like Unity Biotechnology already conducting human trials, Aubrey de Grey is bullish about the sector. "The field of targeting senescent cells has completely exploded. And I would say that it's now become the highest profile area across all the hallmarks of aging. But there's definitely a spectrum of degrees of understanding - there are some people that understand the whole thing really well, and some people who don't."

A simplistic view of the field is that senescent cells are bad for us, and, because there are more of them in older people than there are in younger people, they are associated with aging, so we need to reduce them. "I use the term "death-resistant cells", which doesn't have any connotations about what kind of behaviour the cell is engaging in that is somehow undesirable. It just emphasises the fact that the reason these cells are accumulating, is because the body is failing to get them to commit suicide (apoptosis), which is what normally happens with bad cells."

And de Grey believes that there are "a whole bunch" of questions about how we might go about reducing the number of senescent cells in our bodies. "The most simple way, and something I originally didn't really believe would be possible, is to find drugs that are able to selectively make senescent cells unhappy, and cause them to commit suicide. And it turns out one can find those drugs. The field as a whole is barrelling forward with a wide variety of different synthetic drugs that can induce apoptosis selectively in senescent cells, by a variety of different mechanisms. And that's wonderful. However, pharmaceuticals are always going to have some limitations, they're always going to have some degree of non-selectivity, some toxicity to the cells that we don't want them to kill, and some cells that we do want to kill that they will fail to kill. So it still makes sense for us to consider alternative approaches."

With so much work going on, and so many different ways to tackle the challenge of senescence, there are still no Phase 3 trials in this field. But de Grey believes we're not far away. "I think it's close. Unity Biotechnology are still ahead of the field in terms of progress, the trial that failed last year with a Phase 2 trial, but they've got two other trials in Phase 2 for other indications - they're covering a lot of bases. They're well-funded, they're a really good company, they've got everything going for them, and I think we could be talking no more than a couple of years before we get things through the process."


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