I wrote here a while ago on the topic of “senescent cells”, which has been a hot topic for quite a while now. It’s an appealing hypothesis - that there’s a population of cells that has lost its oomph and are not only not contributing to their respective tissues, but could even be actively dragging them down. They have stopped going through the cell cycle; they have different protein expression profiles and different secretory profiles, and there’s evidence that clearing them out might improve overall health. Why, you ask, hasn’t evolution gotten around to this useful effect already? Probably because natural selection is no longer really operating very strongly on cellular events that only happen in older individuals. By a certain age you’ve either passed on your genetic heritage already or you’re increasingly less likely to do so at all, and you are thus basically invisible to natural selection.
Here’s some of the latest news in the field, the start of a clinical effort to try senolytic therapy in Alzheimer’s patients. I’m very much in favor of Alzheimer’s ideas that don’t involve direct attacks on the amyloid pathway, since I think that so far the evidence is that those aren’t very useful at all. This trial is the very first tiptoe into the clinic - five people, open-label, Phase I. You can’t start off much more tentatively than that! These patients were given a combination of dasatinib and quercetin (“D&Q”, in the lingo of the field), which are two of the better-characterized compounds in this field. The former is a well-known inhibitor of several tyrosine kinases, and the latter is, well. . .I’m not sure what quercetin does, to be honest, but it has been investigated in this field and in many others. The combination of the two has cleared senescent cells selectively in culture and in animal models.
Full article (open access):
https://www.science.org/content/blog-post/senolytics-clinic
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I have tried the D&Q protocol using 100 mg of dasatinib two days each month for 5 months. Subjectively, I have felt zero results and saw no significant change in any of my blood markers that I normally test. I probably will keep on doing it for a while just because I have a supply of it.
On another note, I have been using 100 mg of dasatinib in a mixture of 30 mL of Transcutol and 70 mL of water in a fine mist spray bottle for just a few weeks. Subjectively, because it is something that is hard to measure even though I take some skin selfies, it is working much better than the rapamycin mixture in reducing, age spots, and wrinkles. It actually seems to be tightening the skin. I really do notice, and it may be my imagination, that my skin looks much better in the mirror. The thing that I really notice a difference in are the age spots on the back of my hands.
To be honest I didn’t really notice too much, though there was some difference, using the rapamycin spray.
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@desertshores What is your CRP score these days. It may be that your other protocols have given you a very low senescent cell load. Senolytics without the presence of senescent cells won’t really do much…
Rapamycin, taurine and Metformin all reduce senescent cell load.
My last test was ~1 year ago and it was 0.5 mg/L. I have another one coming up soon.
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Now, Armstrong is leading a trial of 50-60 childhood cancer survivors with signs of frailty, along with blood-based markers that indicate a significant amount of senescence. Aged about 40, on average, the participants will receive oral doses of either dasatinib and quercetin, or fisetin, to see whether it can improve their physical function over the course of six months. These individuals will then be tracked every five years to assess whether this treatment can help extend their life expectancy.
For researchers into ageing around the world, such data represents a first tentative step towards indicating whether senolytics could one day be used as a way of extending healthy lifespan in all older adults.
Grillari – who is also co-founder of Rockfish Bio, a company that has developed its own senolytic – is now hoping to launch trials in other disease states, as well as using the company’s senolytic to try to rejuvenate organs from older donors.
But many are urging caution. Prof Tohru Minamino of Juntendo University in Japan, who has studied cellular senescence for two decades, points out that some senescent cells are beneficial to our body, playing important roles in key physiological functions such as wound healing. Simply clearing away everything could have negative long-term consequences.
Minamino believes that he may have the answer. In 2021, he and his colleagues unveiled an “ageing vaccine” that uses a protein called GPNMB to selectively remove senescent cells that contribute to inflammation. “We’re trying to specifically target the bad guys,” he says.
Once again, this has been shown to work remarkably well in mice, with older rodents showing fewer functional impairments after receiving the vaccine and living substantially longer. Minamino is now hoping to develop this as an RNA-style vaccine, similar to the Covid jab, which trains the immune system to remove inflammatory senescent cells and could be used in patients with Alzheimer’s, chronic lung disease or frailty.
@kpfleger a new senolytics company I didn’t see in your list on your website:
https://www.rockfishbio.com
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ng0rge
#7
Good article! This is the paragraph that I noticed.
“One of the challenges at the moment is that we don’t have particularly good tools to estimate the number of senescent cells in the human body and the extent to which this changes with treatment,” says Minamino. “But if we can develop better imaging systems for measuring how these cells are accumulating, you can envision a future where this could be part of an annual medical check.”
What about SapereX? @nym ?
“Your body still needs to have the capacity to regenerate,” he says. “There’s still an open question about what would happen if we get rid of the senescent cells, but there’s no reservoir of new cells to replace them any more because your stem cells are no longer working. We are going to move this way in the future, treating more and more older people, but for now we first need to gather more evidence that senolytics can really work in humans.”
Why not follow the “protein called GPNMB to selectively remove senescent cells” with targeted stem cell therapy?
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nym
#8
SapereX was available to few clinics as a research tool to collect use cases, refine test interpretation etc. We are launching to US-based physicians in a few weeks.
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@RapAdmin Rockfish has been on the “to be considered” tab of AgingBiotech.info/companies for since at least Aug, but like many other companies on that tab, it is still pre-clinical and “currently seeking funding” according to its website, so not quite clear that it will amount to much. Only 7 people associated with it according to LinkedIn currently. There are 100+ companies of that early stage on the “to be considered” tab and I’ll work through them eventually but they aren’t top priority because of how far away they are from getting through trials.
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