In this article you will learn:
What senolytics are and why they may be important for aging
How they work and what options there are, as well as what considerations to have when using them
The Details:
One of the proposed reasons why we age is that there is an accumulation of senescent, or “zombie” cells in our body (cool thought, huh?). These cells have stopped dividing and growing, and they leak toxic chemical signals to nearby cells that create a whole host of effects which contribute to aging. Senescence is a normal part of our biology and actually has many roles like protecting against cancer or aiding in tissue repair,(1) but as we age, it gets out of control and modern anti-aging efforts have sought to create novel therapies that aide in controlling this microscopic zombie apocalypse through the triggering of apoptosis, or programmed cell death.
When you fast, your body does this naturally after 24 hours, but certain compounds have been researched for their specific senolytic effects. One in particular, spermidine, aides in promoting the process of autophagy, or cells' self-destruction.(2,3) It does this by mimicking the effects of a calorie restricted diet, and the early research on animals and in test tubes shows promise that spermidine may extend life.(4)
Spermidine is part of a group of important nutrients called polyamines, which are responsible for many important growth and protective functions in the body and they decline as we age.(5) Some studies looking at the safety of spermidine as a supplement showed no toxicology in both rats and humans, so ingesting it in higher amounts may be something beneficial.(6) Although still in its infancy, the clinical research on spermidine is promising and shows possible benefits on heart health, cognitive performance and even hair loss.(7,8,9,10)
Yet, critics argue that you can obtain your polyamines from a healthful and well-rounded diet of vegetables, grains and meat.(11) It’s also not yet possible to measure autophagy directly in the body, let alone something you could keep track of easily with an at-home test or testing you can order online. Other senolytics exist, like the plant compound fisetin, but the research is sparse and some in the anti-aging community have argued that their use may actually be detrimental for health, as compared to rebooting those cells through proper nutrition and other methods, like telomerase therapy.(12,13)
This is because polyamines, the group of compounds spermidine belongs to, can also
contribute to oxidative damage seen in pathogens and cancer when there is an imbalance of them in the cells.(14)
This doesn’t mean you should avoid spermidine necessarily, but the research on polyamines and their metabolism is still in its infancy. We really don’t know the full extent of how these compounds react and under what circumstances they may be toxic or beneficial.
My own approach in this area is guided by the same question I use for everything else:
What could I get for the cost of this intervention if I spent it on things I know are already important?
At the time of this writing, spermidine as a supplement is barely making its way into the market and the cost is about $150 for a month’s supply. A company called Longevity Labs produces a spermidine supplement named spermidineLIFE and it comes with about 2mg of spermidine per serving for a 30-day bottle.
The downside, besides being unable to measure autophagy, is that this product is sourced from wheat germ and contains some gluten. According to the company, it’s only about 2mg of gluten per serving of 2 pills, but this may be an issue for some people.
In the end everyone wants a miracle pill, but for that same amount of money you could get almost all of your Everyday Basics and I’m just not convinced that the trade is worth it for something I can't measure. Especially without a way to compare it to already established clinical evidence (i.e. you need vitamin D for a good immune system, we aren't sure if or to what extent you "need" a spermidine supplement beyond getting it from diet) it’s just not clear enough either way to justify the price yet.
Regarding the other compounds, like fisetin, that are basically fasting mimickers - the same goes as before. My take is that these are expensive and difficult to measure. If you are sticking to good principles, it will be even harder to measure because it's difficult to say what the difference is between good habits (nutrition, eating mindfully, supplements, etc.) and taking these substances.
If you are older and looking for a boost, my personal advice would be to align your habits first. Get a grip on your eating habits, circadian rhythm and what you say "no" to every day. Manage your stress, practice Gratitude, have a life that is full of purpose and cultivate great relationships. All of these things have been extensively researched to extend your life without any side effects.
References
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128428/
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287690/
4. https://academic.oup.com/ajcn/article/108/2/371/5046172
5. https://www.frontiersin.org/articles/10.3389/fnut.2019.00108/full
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807086/
7. https://pubmed.ncbi.nlm.nih.gov/30388439/
8. https://pubmed.ncbi.nlm.nih.gov/29315079/
9. https://pubmed.ncbi.nlm.nih.gov/31137855/
10. https://pubmed.ncbi.nlm.nih.gov/29214104/
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022763/
12. https://www.lifespan.io/news/are-senolytics-potentiallydamaging-for-longevity/
13. http://www.lidsen.com/journals/geriatrics/geriatrics-03-01-034
14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290137/
