D+Q+F+P+L+G+GLA: A New Senolytic Cocktail
For my May 15-18 senolytic session I tried something new. In a recent Foresight Institute talk available on YouTube, James Kirkland identified the flavonoid Luteolin as a senolytic. There have also been reports that GLA and Gingerenone have strong senolytic properties. Therefore, on the theory that in a senolytic session the more different senolytics the merrier, I decided to combine these three with the D+Q+F+P senolytics that I has already been using. It is not clear how much of the new items one should take, so I had to guess. And so, in late mornings of this past Sunday, Monday, and Wednesday I took the following senolytic cocktail:
1 x 50 mg Dasatinib (From India; I usually take 100-200 mg, but only 3 tabs left)
4 x 475 mg Quercetin (Swanson)
10 x 44.5 mg Bio-Fisetin (Life Extension protected caps with x25 bioavailability)
1 x 10 mg Bioperine (Swanson)
8 x 165 mg Luteolin (Geroprotect Autophagy Renew)
10 x 200 mg Ginger Root Extract (Swanson, Gingerenone amount unknown)
5 x 400 mg Mega GLA (Life Extension, with 10 mg Sesame Lignans)
That’s a dismayingly large number of tablets and capsules, but for these three sessions I took them with water all in one sitting. On Sunday evening following the first session I experienced a mild headache, mild intestinal cramps, and a feeling of unwellness. On Monday evening I experienced stronger versions of these symptoms, plus frequent bowel movements and a mild fever. On Tuesday I was scheduled for a 12:15 PM dog-agility training class, and I felt unwell enough that I almost skipped it. My performance at class was sub-par. When I returned home from it, I decided to defer the final Tuesday senolytic session by a day. I went directly to bed and took a long nap. On Wednesday I felt better, and I did the final senolytic session at about 11 AM. This time the side-effects were not as strong, but I had a bowel movement that included a rather strong burning sensation, which I suspect was due to the exit of the Ginger Root Extract. While I was sleeping last night from 3-7 AM I experienced mild intestinal cramps. On Thursday (today) all the negative symptoms are gone, and I feel very well and energetic, with no bodily aches and pains at all.
I attribute the negative side effects described above to (a) the residue of cleared senescent cells in my bloodstream and (b) the presence in my digestive system of molecules that are usually not present and are temporarily producing intestinal inflammation and cramping (and clearing senescent intestinal cells). The observed effects were quite a bit stronger than I had experienced with D+Q+F+P sessions in October and in February, and I think the three added ingredients are achieving increased senolytic action and perhaps are clearing senescent cells of more diverse cell types. I take the mild headaches as an indication that senolytic molecules are getting past the blood-brain barrier.
All in all, I think my experiment was a success. I plan to repeat the use of this cocktail for my next sessions in August.
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Is there any way of measuring senescent cells in the human body? I am afraid we may be poisoning ourselves without a proper way to measure to see what is happening to our bodies. Feelings can be deceptive as many feel great after recovering from major illness, but it is doubtful if the illness was beneficial. The best forms of proof for me would be hair regrowth or spot removal (i.e. liver spots) or some other physiological change that can be measured. Is there anything out there to prove senescent cell removal in vivo? Thanks...
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Chris M
There are methods of measuring senescent cells, but no really cheap and satisfactory way:
(1) The senescent cells in a tissue sample can be stained to indicate the presence of beta-galactose (SABG, a signal of senescence) and counted with a microscope. That requires an autopsy or a biopsy, however.
(2) In April-2021 Judy Campisi reported that the molecule dihomo-15d-PGJ2 was a unique indicator of the destruction of senescent cells. It should be present in blood and urine after senolytics, and would come from the whole body, not just the blood. In principle, it could be detected with an ELISA test, but I'm not aware that anyone is offering one.
(3) The firm Jininiti offers an assay in cells from SABG in a blood sample. That indicates immunosenescence, but doesn't say much about the rest of the cells in the body.
(4) Dr. She of Jinfiniti has constructed a Senescence Panel (Jinfiniti Precision Medicine). This includes SABG, 4 SASP (IL6, IL8, IL1b and TNFa) and a proprietary and unique NAD test. That would cover a good fraction of body cells and use multiple ways of assessing senescence. However, it is sufficiently expensive that doing before-and-after senescence panels along with a D+Q+... senolytic session would be out of my price range. Someone with deep pockets should do it and report the results for the rest of us.
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Chris M I think CRP is useful as it depends in part on IL-6 and is not particularly expensive to test for.
There can be problems when CRP goes too low for the sensitivity of the test, but I think it is helpful.
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John Hemming Thanks. I think that is probably the best thing to go on. It also seems that inflammation is a key component of a lot of epigenetic age tests as well. Sometimes I wonder if they should call them inflammation tests that compare inflammation levels at various ages.
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Chris M
My view is that it is in fact the IL-10 levels in groups of cells that drives this. IL-10 is part of SASP and is in theory anti-inflammatory. Because it drives down NF Kappa B, the citrate carrier is down rated in the mitochondria and cells fail to differentiate.
However, IL-10 is hard to measure and although CRP is affected by more things than IL-6 it is a workable proxy.
My own view is that cell differentiation (via acetylation) is the key to this rather than methylation patterns.
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John Hemming
Yes, CRP tests are cheap. At the moment, Life Extension does their CRP tests for $31.50. I have tested and noticed some decrease in the CRP level following a senolytic session.
However, the CRP level also depends on other things. A few years ago I stumbled over a chair in the dark and received rather spectacular bruises on my right leg. My CRP level shot up until the bruising went away. Also, I note that the Levine Phenotypic Age calculation used the logarithm-base-10 of the CRP value to take into account the large variations it may have.
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JGC IL-6 has a similar problem. CRP is a good compromise people need to be aware of its limitations.
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I've long been fond of CRP testing, and short of more accurate & inexpensive tests to measure senolytic activity, it may be best. However, almost all medicine & even holistic drug recommendations are based on weight. Far more accurate, & useful, would be to include age, health conditions, etc. For instance, CRP is mostly to catch over-all inflammation, which is likely root of all disease & aging, but shouldn't individuals with cancer, take more -- and/or more frequent -- dosing?
Separately, maybe 30 years ago, as an LEF member, I did blood work through them, and despite checking the appropriate boxes, LEF used my blood results in a study (I found out through another error by LEF.) And with LEF, publishing my results -- even without my ID -- is with purpose of selling various LEF products. That & other experiences, have resulted in my not trusting LEF, although I still use some of their products, although buying from AMZN is same price as being an LEF member
