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Comment by reasonattlm | Hacker News Reader

Actionable things for humans at the moment appear to look like trying senolytic drug candidates in rational self-experimentation, with before/after tests of metrics linked to tissue stiffness, inflammation, kidney and heart function.

Clearing senescent cells very clearly produces a degree of rejuvenation in mice, and can turn back progression of aging and specific age-related diseases via a sizable number of metrics.

Of those senolytic drug candidates, dasatinib plus quercetin if you're fine with short burst of chemotherapeutics, or FOXO4-DRI if you are fine with using peptides lacking human data. Both of which should be filed under the "risk that needs to be well understood" category. Or you could wait a few years for the first human trials to run through and more data and better drug candidates to arrive.

But these things are on the menu of possibilities, and are not expensive at all to carry out as exploratory tests.

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The problem with all potential senolytic drugs is cancer. Looking at all the animal models (and spontaneous human mutations) where senescence is reduced there is a corresponding increase in cancer. We really can't do much about ageing until we can cure or prevent cancer.

That would only be the case in the models where senescence is blocked completely.

If instead for a short time killing some fraction of all currently existing senescent cells, the effect on cancer risk should be a reduction, due to decreased inflammatory signaling from those cells. The senescent cells that are hanging around at any given moment in time aren't helping you in any way; they're not reducing the risk of cancer. If there are enough of them, they are in fact increasing the risk of cancer due to messing with the surrounding environment. If those senescent cells ever actually helped, then that help was applied at the time the cell became senescent - and shortly thereafter it became a liability that should be destroyed.

There are emerging exceptions to that view, such as adaptive senescence in the immune system and possibly in support cells in the brain, but fortunately both of those should be largely moot points for the early senolytic therapies, and don't seem to be obstacles in old mice.

> trying senolytic drug candidates in rational self-experimentation

> senolytic drug candidates, dasatinib plus quercetin if you're fine with short burst of chemotherapeutics, or FOXO4-DRI

How does one go about self-experimentation? FOXO4-DRI is for sale on the internet, but one needs a doctor to read the mouse studies and formulate a treatment plan. The same goes for dasatinib plus quercetin. In the mouse models it needs to be administered monthly. Is there a country one can visit today that has access to these peptides and drugs and willing doctors to create a plan?

I'll get to publishing a detailed essay on that topic at some point in the near future. The less detailed precursor overview can be found here:

https://www.fightaging.org/archives/2017/05/planning-a-singl...

You don't need a doctor to figure out a treatment plan, you just need to put in some time to get familiar with reading research papers, the terminology, how researchers describe things, and the methodology used to move from animal to human exploratory studies. And an understanding of the risk - as doctors are usually pretty bad at explaining that in any case. It really isn't rocket science, and it is all copiously documented in scientific and other literature.

Also D+Q isn't administered monthly, it is a one-off treatment that, assuming it works in humans in the same way it does in mice, certainly wouldn't need to be done more than once every few years. It removes the cells it can remove, and then isn't going to do any more until new senescent cells arise at their slow pace. The people out there taking it frequently as though it were a supplement are just not acting sensibly, and don't understand the research.

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