"Senolytic Activator" and Extended Fasting …
Gentlefolk,
Our fine friends at Life Extension have released a new product, Senolytic Activator. It is a combination of Quercertin and Theaflavins. They intend us to use it weekly as a non-prescription version of the Dasatanib + Quercertin senolytic therapy. To fix multiple metabolic issues, I fast. Weekly I have a 24-40 hour fast and monthly I implement a 5 day extended fast. I also implement a 16:8/2MAD time restricted feeding pattern.
My fasting patterns are intended to induce aggressive activation of SIRTuin repair pathways and apoptotic reactions. To that end I supplement with NR. In this context, when should I take the Senolytic Activator? The Life Extension folks formally have no opinion on this question.
This question devolves down to phasing. For example, your body enters a different metabolic regime when your liver depletes its local store of glycogen, between 18 and 24 hours from your last meal. Autophagy rates are postulated to increase; growth hormone starts increasing; a whole panoply of other endocrine systems start shifting. That seems to me to be the likely best time to introduce the Senolytic Activator. SA would provide just the slightest nudge to push senescent cells over into apoptosis. Unless, of course, it is the worst time to introduce SA.
When does this august group think I should take the Senolytic Activator? In phase or out of phase with my fasts?
Anon,
Andrew
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DanMcL said:
My approach is that the LE activator is cheap and easy so I'll give it a shot. The problem is none of us have any measure for senolytic activity, except possibly our hair might lose some grey. For that reason as part of my daily biometric I take a mug shot.Hi Dan. Sorry ... continuing on the challenge you are putting on senolytics and biomarkers and my later reply on DNAm, PhenoAge, composite BMs etc ... :)
I just pop into this (a bit old though):
"... At the level of cells, a potential biomarker of aging may be the presence of senescence. Senescence is a condition in which old or damaged cells remain alive but cease to reproduce. This is an important tool in the body’s ability to prevent cancerous tumors from developing. The older a person becomes, the more senescent cells he or she accumulates. Several markers of senescence in humans have been suggested as biomarkers of aging. On November 10, 2011, researchers at the Mayo Clinic published a study in the journal Nature showing that an accumulation of senescent cells may lead to age-related diseases, at least in animals. By removing most of these cells from several organs (body fat, eye, and skeletal tissue) of lab mice, the investigators were able to significantly delay the onset these diseases, or stop their progression if they had already become established. The study suggests what may prove fruitful areas for future researchers to explore in the search for true biomarkers of aging..."
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Bizarrely positive initial experience with LEF's SA.
I'm new to this group and not engaged in any particular program or mode of life extension. No regular fasts or formal age-reduction protocols. I am, however, a physician in active practice, 80 years old, in excellent though not perfect health for my age, and interested in extending my life provided the quality is good. I'm also well versed in what data is valid and what isn't, at one time was on the editorial board of a respected medical journal. In my personal and professional life I'm quite open minded to alternative therapies as well as knowledgeable about conventional ones.
I've used the SA product for just 2 weeks and experienced some surprising early consequences.
A big issue, of course, is in self-experimentation how can one know if a strategy is or is not "working" -- or conversely, whether it is or is not doing harm. The conventional answer, of course, is that research must be done with proper controls, replication and long term follow up. Yet that takes time, and time is one thing we have in limited supply. Which is why we self-experiment and don't wait -- especially as we near the end of our shelf-life when it will be too late to reap benefit.
Exciting thing about senolysis, however it is triggered, is that it's darn near never too late for it to have at least some benefit. But still the same question: how do you know if it helps. Pictures, physical tests, etc can only go so far. Subjective experience may be best (am I still alive? If so, how do I feel, function?) but it's also unreliable for many reasons I'm sure all of you know.
And yet... I've tried the LEF senolytic activator product for the past two weeks... expecting pretty much nothing, at least at first. Also, I'm sure I'm probably an outlier in terms of my responses... yet results have been remarkable and unlikely to be by chance. Within a few days of the first I noticed:
(1) spontaneous thinning, lightening and shrinkage of a few small seborrheic keratoses on my face without any concurrent topical treatment, scraping, cleaning. WTF?? Without treatment these nonmalignant buggers only get darker and thicker...
(2) increase in energy, especially in the morning, every day, not just right after taking... the subjective experience of feeling as alert in the morning BEFORE my morning 2-3 cups of coffee as I had previously felt AFTER it... though the coffee still adds more. To sure this is subjective, but it was both unexpected and compared to a baseline of many months...
(3) quite noticeable improvement in perceived brightness of shadowed or dark areas, such as fading/poorly maintained white lines on roads at night. Unlike many at my age I still have been comfortable driving at night, though a predictable age-associated change in vision -- independent of cataracts, macular degeneration, etc -- is simply less sensitivity to light. Dim areas look darker, etc. About a week after starting the SA these areas were perceived as brighter... an effect neither expected nor looked for... e.g. areas in a bathroom lit by the same dim blue-blocked night light now look fairly bright instead of shadowed; and driving at night, it no longer seems most road markings are way past their time to be repainted... If I had expected such results I might have tried eye charts before and after to quantify any changes in vision. But the subjective changes have not been subtle.
I realize even if SA is working, such rapid changes are not expected. if didn't experience them myself I might not believe them. Yet the combination of my spontaneous observations leaves me feeling no doubt that it is doing something pretty good for ME. What does this mean for anyone else? Who knows? And there's still the question: should I follow LEF's recommended schedule? Stop taking it sooner? Continue indefinitely? Increase the default interval of one week? Add or substitute fisetin?
I know testimonials prove nothing, but thought I'd share this. Lots of questions unanswered. Yet in my personal experience, rather mind-boggling and improbable, I'm convinced LEF has stumbled on (or figured out?) something can work, at least for some.
Jon Russ MD
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Thanks for thoughts/advice... after the 2 month weekly use of LEF's SA I plan to take a break... perhaps do 3-4 courses/year though would depend on how well the perceived benefits sustain.
I am flummoxed if pleased with the rapidity of my response to the SA product, which is sustaining with further gradual progress -- regardless of how many senescence cells I may have accumulated in 80 years... I do take some other things that might be relevant including metformin 500-1000mg/day; I'd been diagnosed with borderline diabetes a few years ago and initially improved my blood sugars with diet and lifestyle changes alone. but added metformin a few months ago not because I had to but figuring the less glycation the better as well as metformin's possible life extending effects.... [FYI metformin did not result in anything noticeable, though I tolerate it well.] Perhaps it has a synergistic effect in synergy with the components of the SA product.
Then again, I have had unusually robust and rapid responses in the past to some things that might have a hormetic effect such as brief but high intensity exercise regimens.
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I continue to have progressive benefits associated with weekly dose of LEF's SA. In addition to "age spots" fading, I've also noted flattening and fading of a few small "cherry angiomas" on my forehead. Beard hair that was already a mixture of white and brown is more dark. Alertness further improved, sight in dim light further improved. Accuracy touch typing (in which I've always been fast but variably inaccurate) is better, more like I was used to, uhmmm, perhap 10 years ago? In addition to metformin, another supplement I regular take is the "Curcubrain" product of curcumin. I note a recent review of possible senolytics (by no means all-inclusive) ranked curumin as 2nd-best to fisetin.
Sorry, I don't have the patience or the time to rigorously "test" all factors in my personal experimentation, though if I were more interested in proving something than in my own personal experience I might do so. Perhaps at 80 I feel I have less time to "waste."
I'd like to emphasize though I've been taking curcumin for several years and metformin for around half a year, I'd never notice any effects of note until I started the SA. Of course, that doesn't mean there may not have been any anti-aging processes going on, just none heretofore noticeable to me. (Perhaps this reinforces the unlikelihood of my SA experience being a placebo response.)
Oh, I haven't noticed any darkening of my urine since being on SA. I strongly doubt such happening after several days' fasting reflects death of senescent cells, though that's a nice thought -- more likely from catabolic breakdown of amino acids, as one source reported, "In addition to known markers (plasma free fatty acids, glycerol, ketone bodies) that reflect changes in the body’s fuel management under fasting conditions a wide range of “new” entities such as α-aminobutyrate as well as other amino and keto acids were identified as fasting markers."