Cell survival, suicide and how to kill them

Unfortunately I did not get this blog finished by my goal (I was hoping to post it yesterday, and it still isn’t finished). So there are a bunch of $*$* flags throughout this post.

But I would like a little feedback on it, so I have posted it as is. Here are the additional topics I hope to cover:

[$*$* This article needs a lot of work. Expand who figured out senescent cells; who first experimented with them; how the experiment was done; when senolytic drugs were first found; how the experiments went; the growing number of people using senolytics; how it is being commercialized; etc.]In humans, any population of older cells will develop senescent cells. These senescent cells should commit suicide (apoptosis) or be killed by the immune system, but in older people increasing numbers of these senescent cells survive.

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These senescent cells do not do their proper function for the tissue they are in. This would not be so bad if they didn’t also emit a large array of damaging proteins that cause inflammation, cancer, and otherwise damage the local cellular environment.

Eliminating senescent cells was first done in mice by the University of Minneapolis in 2012[$*$*verify]. They genetically modified the mice so their senescent cells could be stimulated to apoptosis (kill themselves). This experiment was a great success, extending the lifespan of the mice by 20%.

Since then additional studies have found drugs that can cause senescent cell apoptosis. The first 2 to be researched were diastab and quercitin, a drug combination which clears many senescent cells from mice. More recently fisetin has been found to do the same thing. Now there is a company which is trying to create a drug that works better (none of these can eliminate all the senescent cells from a mouse). Some of these drugs, called senolytics, are available as a supplement over the counter and some are very expensive prescription drugs. Fisetin is a senolytic drug found in strawberries and if you ate enough strawberries you should be able to obtain the same effect as taking the drug, though it would take longer.

A pound of strawberries has about 75 mg of fisetin. It is estimated that 500 mg of fisetin is needed per day for 5 days to treat a 135 pound person. To get this amount of fistetin from strawberries you would need to eat nearly 7 pounds of strawberries a day. That is not really feasible, but you might be able to eat somewhat less for a longer period of time.

While there are a number of self-experimenters around who are taking senolytic drugs regularly, this is not considered wise nor a means to extend lifespan. They should consider what they are trying to do (kill the senescent cells) and what happens if you take drugs all the time (given time, senescent cells may ‘learn’ to evade the drugs). It is best if you took senolytics like they treat mice: you give a course of drugs to eliminate the senescent cells and then you wait for (years?) for the population of senescent cells to build up again before taking another round of drugs. Unfortunately there is not any way (yet) of determining your senescent cell load (number), but I hope that technology is coming soon.

Unfortunately not all senescent cells die with our current drugs. Some remain, so multiple different drugs may be needed to eliminate more than a small fraction of the senescent cells. For example diastab & quercitin manages to eliminate about 40% of the senescent cells in a older mouse.

Fasting has also been rumored to clear senescent cells. I suspect this is one of the reasons many people feel better and have better health when they fast intermittently. But so far there is no way to tell if senescent cells are being killed without doing a biopsy. Hopefully someday soon urine (best) or blood (not so good) work will be able to detect when senescent cells have been killed. If there were some test (like testing urine samples for indicators that senolysis is occurring) then it would greatly simplify doing senolytic experiments. It would also show when the drug has been optimally successful and the treatment should end. Hopefully science will develop this capability soon.