"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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  • Hi Andrew,

       I also engage in 5 day fasts twice a year, with overnight 12++ hour fasts. I also have the LE Senolytic Activator you mention. Personally I wouldn't take a senolytic activator during a fast, for one reason it would likely kick you out of the fast! Or something to that degree, the activator is not zero calories I assume. Plus your digestive system shuts down and takes a rest, I doubt it would either feel good or effectively digest if you took some supplements. So I recommend using it while not fasting, as I'm doing now. 

     

    I'm not overly convinced of the value of the SA product, so I'm testing. At least it's cheap and easy. 

    Reply Like 1
      • adonoho
      • adonoho
      • 10 days ago
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      Dan Mc Hi Dan,

      Thank you for your reply. I've already taken it on day 3 of a 5 day fast. If we judge by my ketone levels, it did nothing to my fasting process. My bigger question is whether we can help SA do its job of pushing senescent cells over the apoptosis threshold by fasting. As most of my inflammation markers are quite low, I doubt we could see a change due to SA. My current plan of record is to dose SA at hour 24 of my weekly 40 hour fast. I'll keep folks posted.

       

      Anon,

      Andrew

      Reply Like 1
      • DanMcL
      • skipping my funeral
      • danmc
      • 10 days ago
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      adonoho OK good you've tested it's fine during a fast. It's an interesting approach.

      To answer you question I really don't know, and I'm not sure a hypothesis could be made. Fasting activates some alternate genetic pathways (epigenetic) which may respond more or less favorably to senolytics. Normal cells 'bunker down' and 'harden' themselves via this to deal with ketosis and famine. Cancer cells, being unstable, usually don't have this ability (some cancers adapt to fasting). So fasting and chemo is an excellent pair (see Voltor Longo's work on this). What about Senescent cells? Depends on how abnormal they are I guess, I could be that they, like cancer cells, are weakened by fasting. Or they could be strengthened just like normal cells. 

      Reply Like 1
  • Directions for LEF Senolytic activator is 2 caps once a week for 12 weeks. Does this effectively replace dasatinib/quercetin protocol?

    Reply Like 1
      • DanMcL
      • skipping my funeral
      • danmc
      • 9 days ago
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      Suzanne I think nobody knows the answer to that, we'd have to do a direct clinical trial on both. LE might have an estimate though, I've found if you send them a product query they're excellent at replying with what they think. Carefully worded of course. 

      FWIW, on the one hand plants are basically chemical factories, and most or many drugs come from distilled plants. Dr Peter Attila said when his patents tell him they'd rather have a more 'natural' approach via supplementation he asks why, when supplements are basically unregulated drugs? So in theory it could be as or more effective. 

      On the other hand the only work here is LE went through a database of parameters from plants and found a combination believed to be similar. So again no idea. 

      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. 

      Reply Like 1
      • adonoho
      • adonoho
      • 8 days ago
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      Suzanne It is clearly less effective on a per dose basis than dasatanib+quercetin. Does the full course equal the dasatanib dose? Unknown but unlikely is my guess. Does it offer some benefit? Likely. How much? Unknown. Hence, my question about taking it during fasting, i.e. could I make it more effective by stressing the senescent cells. Basically, if it can induce some of my senescent cells over the edge, then it is probably a net win.

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  • This is kind of moot, since there's no evidence that the theaflavin + quercetin supplement actually kills senescent cells: see my post here.

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