Friday, March 29, 2019

Senolytic Self-Experiments


I’ve written about this before but I think it worth going over again to clarify it in my own mind and for the interest of others.

Over the last few years I’ve read a lot about longevity and increasing healthspan. I’ll admit this is not for the usual reason I read science articles (grist for the writing mill) but for selfish reasons. Like anyone of my age (now 58) I am at the point where, for some years, I’ve noticed things are beginning to break down. Over five years ago I was a drinker and a smoker. In my thirties when I drank excessively and didn’t really suffer hangovers, but they came and steadily grew longer. At one time I smoked rollups without filters. Chest pains introduced filters, then nicotine gum in the mornings to delay the first cigarette, and an inhaler to open up my airways so I could sleep. Anxiety and depression kicked in after the death of my wife. This stopped the drinking because alcohol is a depressant with the aftereffect of anxiety, meanwhile a bigger focus on health along with the arrival of the electronic cigarette stopped me smoking. 

My health improved markedly from stopping these and from years of exercise to counter the anxiety. My anxiety waned and this steadily revealed that even with the improvement in my health, aging was having its effects, of course. Throughout this time, for the anxiety and looking for health improvements, I investigated and took all sorts of vitamins, herbal remedies and nootropics. This led into reading about longevity and healthspan, whereupon I discovered stuff about senescent cells and the substances that target them, senolytics.

A senescent cell is a kind of zombie cell. It goes wrong and instead of entering apoptosis (cell death) it goes into senescence, which means it won’t die but it also won’t replicate. The theory is that it does not sufficiently broadcast its damage for the body to destroy it; that the partial shutdown is a response to prevent it becoming cancerous. However, in that state it produces inflammatory chemicals that disrupt healthy cells around it. More and more of these accumulate as we get older and scientists are steadily revealing them as a root cause of many of the diseases of aging. If only we could take something to kill them off. . .

A gobsmacking study on mice appeared. It had been discovered (somehow) that a combination of the cancer drug Dasatinib and the supplement quercetin were a senolytic. When given to aged mice their health improved markedly throughout their bodies and it extended their lifespan by 36%. Many people began experimenting with this combo and I too considered it. Unfortunately trying to get hold of Dasatinib is a risky business since it is prescription only. There are many places that sell it, especially in China, but will you actually be getting the real deal? I’ve also yet to see much on any positive effects from the self-experimenters. I put the idea aside, since I’m not dead yet, and continued reading.

After the success of the above combo (in mice) researchers began looking for other senolytics and testing them. Two were highlighted: fisetin, a flavonoid like quercetin but found in strawberries and piperlongumine a constituent of the long pepper. Fisetin it turned out was better than Dasatinib and quercetin, it also has no known ill effects when taken by humans and is a supplement you can buy. I read the mouse study and made the calculations – there is a formula to convert from a mouse to a human based on skin area. It turned out, that to do the equivalent of the mouse study in me, I would need to take (roughly) 640mg of fisetin per day, with some form of oil since it is lipophilic, for five days. I upped this to 1000mgs for maximum effect.

At this time I had also had further health improvements through fasting two days a week and dropping a lot of fat, getting some better sleep through using melatonin, and was still taking a variety of supplements on top of that. I also became a regular gym goer. So one must judge anything I write about this with caution. In no way have I conducted a carefully-moderated clinical trial. At the time I also found it difficult to recover from my work in the gym. I felt very tired all the time. I dressed up my response to this as ‘power napping’ but really it was an old bugger needing to take a snooze. I took a couple of courses of fisetin as detailed, over a few weeks, and felt particularly rough each time – like I was developing a cold – a had anxiety (maybe a nocebo effect since I aimed to kill certain cells in my body). Afterwards I just ate well when not fasting. Had it done anything? I thought not, and I thought that even if it had I might not notice effects. However, some weeks after this I noticed I no longer needed my power naps. This could have been an effect of fasting, or the melatonin or something else I was taking. It could all be placebo. But I found it encouraging enough not to dismiss it, and maybe try it again.

What percentage of my senescent cells did it destroy, if any at all? How quickly do senescent cells build up in the body? These are questions I simply cannot answer. I decided to try again on the basis that I probably still had plenty of senescent cells in me and the side-effects aren’t too nasty. Last Sunday night I took my first dose. On Monday I took another while fasting through till Tuesday (beginning with a dry fast of 16 hours) – 40 hours in total. I took doses through until Thursday. I felt particularly rough. I had symptoms of a developing cold again, a cold sore attempting to break out, feelings of extreme cold even when eating (so not an effect of fasting), a crappy mood and a lot of anxiety. I needed to have a sleep during the last day and that lasted two hours, followed by eight hours that night. I am now into my first day without a dose and am recovering quickly. 

Again I must make the point that this is in no way scientific. However, I simply cannot put the nasty effects down to anything other than the fisetin. This is also confirmed by someone else who has done the same as me. Perhaps such large doses just fuck me up big time and kill no senescent cells at all. But worth a punt. I will see in the ensuing days and weeks if any positive effects are noticeable. Meanwhile I look to the increasing number of biotech companies developing their own senolytics and putting them through trials. 

Interesting times.  


8 comments:

Lauris M said...

Cool, thanks for sharing. Interested in seeing further development!

Nick Mele said...

Interesting. I find that, ironically, drinking those eight glasses of water help me with fatigue at 69 yrs. old. So does regular exercise, refraining from carbohydrates--I take in 80 grams or less of carbs each day, and in my case, garlic supplements.

Ian M Campbell said...

Neil - Not only immortal in writing now you aim to achieve it in physical form.... Good luck. Will the brain cells remain cooperative and young enough to keep writing good stuff?
Ian.

Subrata Sen said...

Neil, I notice that several people on high dose Fisetin report exactly the same symptoms while different combinations of other supplements and diet, so I'm sure the cold and flu-like symptoms are indeed due to Fisetin. I hope that mens it killed off some senescent cells.

Subrata Sen said...

Sorry for the self-evident thumb typo's.

Subrata Sen said...

Maybe last long enough to transition to AI?😉

Dan said...

You could of course try reducing the dose, since the ill effects might be down to a poisoning effect. A lower dose for longer would be my advice as a biologist (not a medic).

ILTYT_Adventure said...

Interesting times.

Indeed.