Autophagy, Gene Length and Aging (why Senolytics don't work that well)

I have done some analysis based upon the review on autophagy and I think I now know why senolytics don’t work that well.


Question for John. Would you expect senolytics to have a greater benefit for certain tissues based on long gene involvement? I also wonder if most of us are not optimizing the use of Rapamycin to promote autophagy. Perhaps every other month dosing combined with fasting and zone2 training would be better than weekly.


I think clearing aenescent cells is generally a good. However, targeting specific tissues is not necessarily that easy

I agree with the idea of using rapamycin to target cycles of autophagy potentially combined with other tools such as fasting. I think weekly is too frequent.


This is a bit of an overlap paper that I have just found:

Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan

@John_Hemming “weekly is too frequent”. What is your rapa cycle? I understood your long cycle was due to reluctance to interfere with other interventions. For people who are not maximizing the citrate intervention (your protocol requires a lot of attention), what makes sense to you for rapa?

Rapa is about autophagy. It acts by inhibiting mTOR. I don’t want to inhibit mTOR when I wish to grow things (like muscle). What Rapa does is to provide a spring clean, but it also has a long half life (almost 3 days). Hence if you take it weekly you are hardly getting back to normal.

I am now running at a higher frequency than I normally do. I take Rapa every 21 days. (6mg)