Senolytics in the Clinic (Science)

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.

Quercetin and dasatinib, two powerful senolytics in age-related cardiovascular disease

Cellular senescence is characteristic of the development and progression of multiple age-associated diseases. Accumulation of senescent cells in the heart contributes to various age-related pathologies. Several compounds called senolytics have been designed to eliminate these cells within the tissues. In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment. This mini-review discusses the changes in the aging heart and the participation of senescent cells in CVD, as well as the use of senolytics to prevent the progression of myocardial damage, mainly the effect of dasatinib and quercetin. In particular, the mechanisms and physiological effects of senolytics therapies in the aged heart are discussed.

Paywalled paper:

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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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