After looking at the RMR mouse study (link below), it seems that the Gal-Nav senolytic group (yellow dash line) is performing much worse than the control group (solid blue line). Also considering how the Mayo clinic’s senolytic experiments were also a bust, is it time to put an end to senolytics for longevity?
Senomorphics such as Taurine and Rapamycin seem to have far superior results. I guess it’s better to prevent a problem (senescence) than to cure it later!
IMHO, senolytics are probably only useful in topical applications. I will be cutting all senolytics from my stack effective immediately due to a lack of convincing data. Which means that I’m not ordering any more Fisetin, Grape Seed Extract or Quercetin.
If you have any evidence/thoughts either pro/con, please post here to open the discussion. I think I really need more evidence to use oral senolytics and until then, it’s best to avoid them altogether IMHO.
As a final nail in the coffin, David Sinclair recommends using Fisetin.
The molecules I use that are described as senolytics are also HDAC inhibitors. HDAC inhibition is very dose dependent. If you have a strong HDAC inhibitor (I don’t use those) and a lot of it you can get ATP depletion and atoptosis. At a lower level it can skew the balance between transcription and translation such that there is insufficient ATP for translation. However, for Queen Bees it is part of extending lifespan by a factor of maybe 5 times the worker bee.
That may be true, but extra ATP can be provided by preventing cells from becoming senescent in the first place through the use of senomorphics. I see strong evidence for life extension through senomorphics but I am seeing the opposite for senolytics.
I don’t give any thought to senolytics as it seems too confusing to know how to thread the needle. The body knows what to do, I figure. My efforts involve getting out of the way and providing the right stimulus and nutrients. On the other hand my chronic inflammation is very low so maybe I just don’t have a senescence problem … others may benefit more.
That sounds like a sound decision given the data we have. I have no plans to supplement with senolytics at this time. I would need to see more evidence of benefit. However, I do try to eat a healthy diet that contains Fisetin, Quercetin, etc.
A component of grape seed extract was shown to extend lifespan and healthspan of mice:
“To establish the potential of senescent cell elimination to extend the remaining lifespan of WT mice, we performed PCC1 treatment beginning at a very old age (Fig. 8k). Mice receiving PCC1 administration (once every 2 weeks or biweekly) starting at 24–27 months of age (roughly equivalent to an age of 75–90 years in humans) had a 64.2% longer median post-treatment lifespan (or 9.4% longer overall lifespan) and lower mortality hazard (65.0%, P < 0.0001) than the vehicle-treated group (Fig. 8l,m). These data indicate that PCC1 can significantly decrease the risk of age-associated mortality in old mice.”
Unfortunately, that study is a Chinese study from one research team 3 years ago. Based on evidence from other sources, it is looking like it may be “fake news”. I can’t find any research support for grape seed extract outside of this one Chinese paper. Everyone cites this one paper for procyanidins and grape seed extract.
I trust the RMR and Mayo data more than one Chinese study, and they are screaming that senolytics just don’t work. Or at least not as well as senomorphics.
Now senomorphics like Rapamycin and Taurine I believe work much better. In fact, they work so well that they probably overwhelm and outclass any benefit from senolytics.
Why would you buy a second-hand Ford Fiesta when you already ride a Ferrari?
I have used senolytics and I plan to continue using Fisetin a once or twice each year. I base this on my own personal experience. I agree that Taurine and Rapamycin is the better option. But I find room for Fisetin in my health plan.
Seven years ago had a shoulder injury (AC Joint) that would not heal. I had decreased range of movment and pain when I eleveted my right arm. I was not able to swim due to severe pain.
A few years later, I came across a Life extension’s product called, senolytic activator. The original formula (now the formula is changed) was Quercetin and theaflavins. When I used triple the recommended dose, that formula decreased pain and increased pain-free range of movement. But only for a few days. Looking back, the formula worked as a long-lasting painkiller and anti-inflammatory. Was it a senolytic? I don’t know. But it reduced my shoulder pain for a few days.
Then came fisetin, and I tried pure fisetin 30 -40mg/kg body weight, mixed with oil and taken with black pepper. And with this formula I got amazing responses, at least the first couple of times I used it.
Before fisetin I was not able to swim but after 4-5 treatments with Fisetin, pain-free range of movement improved, and I was able to swim with only some residual pain. I had regained almost full functional capacity of my shoulder. These treatments also dramatically increased my libido and the quality of my erections (but only short term for one or two nights).
The last few years, I have not done senolytic treatments on a regular basis.
When I summarize my experiences from senolytic treatments:
I find fisetin useful, at least when I suspect that I have toxic amounts of senescent cells hanging around in my body. When those cells are gone, then there is not much need for further treatments. Continuous treatment might even be detrimental. I plan to use large dose fisetin once or twice yearly.
It seems to me that the view of leaders in the longevity science field are converging towards something like
Optimal senolytics may need to be more tailored to the type of sensense and to different tissues
While this means that the first gen, simple, one size fits all senolytics (as described above on this thread) might not work that well in general, the overall potential for next generation senolytics has not diminished - perhaps the opposite actually - and senescence is still a fundamental, key hallmark of aging that we are understanding better and better and will need to be solved for age reversal.
Think @RapAdmin shared that he saw a similar sentiment when he was at the Buck aging meetings in the fall
Researchers are using new molecules, engineered immune cells and gene therapy to kill senescent cells and treat age-related diseases.
Now, fresh results from animal studies and human clinical trials have added momentum to the field. In mice and monkeys, researchers are using genetic tools to reprogram and kill senescent cells. Others are engineering senolytic immune cells. And about 20 clinical trials are ongoing. Researchers are testing new and repurposed drugs that could have senolytic properties, in the hope of combating age-related conditions, including Alzheimer’s disease, lung disease and chronic kidney disease.
“I am convinced that senolytics will have an impact in the clinic,” says Anirvan Ghosh, chief executive of Unity Biotechnology, a company in South San Francisco, California, that is developing senolytics. “I think the question is really what the agent looks like and what the first approved drug is.”
