31 replies to this topic

[BrentS]

I had my Senescence-associated-β-galactosidase (SA-β-gal) levels measured by a newish company called Jinfinity. Website here:

 

https://www.jinfiniti.com

 

My SA-β-gal were measured at 2190.  That is almost three times higher than the optimal max, which they list at 750.  The blood draw date was 5 Jul 2021.  I got the results near the end of the month, but I had already decided (based on gut feelings, yes I know that is subjective) that high senescence was likely a problem, so I started a Fisetin/Quercetin cycle.  I bought Fisetin and Quercetin from Swanson Vitamins.  But I only bought 3 bottles of Fisetin, as I did not realize how small (100mg) the capsules were.  I started off slowly to test for side effects.

 

6 Jul 2021 - took 500mg each of Fisetin and Quercetin, swallowed them with half a glass of olive oil

7 Jul 2021 - took 1g each of Fisetin and Quercetin, swallowed them with half a glass of olive oil

8 Jul 2021 - took 2g each of Fisetin and Quercetin, swallowed them with three quarters of a glass of olive oil.  I don't like the aftertaste of the olive oil, will try avocado oil tomorrow.

9 Jul 2021 - took 3g each of Fisetin and Quercetin, swallowed them with a glass of avocado oil

10 Jul 2021 took 2.5g each of Fisetin and Quercetin, swallowed them with a glass of avocado oil.  I dropped down because this was all I had left.  Next cycle in 6 weeks I will buy more bottles than 3.  Also I need to find better tasting olive oil.

 

I think the Mayo clinic is doing 2 days on and a month off. but I want to maintain my workout cycle, so I am going to do more days at once with a 6 week break between them.  I noticed no side effects, or any effects at all from the amounts I took. 

 

Once I got the results from Jinfiniti I gave them to my family doctor and asked him for a prescription for Dasatinib, but he is booking me to see a specialist, as he said that is not his area of expertise.

 

Jinfiniti also measured my NAD levels, inside the cells the levels are fine (48.1, which is well into optimal range), but outside the cells and levels are worryingly low (measured at 80, and minimum should be 450+).  I am guessing that the high senescence is causing my body to produce a lot of CD38, which is an enzyme that destroys NAD in the plasma.  I have ordered a large supply of Apigenin from DoNotAge.com, so I will start to take 500mg a day of that when it arrives (will do that for a year or so to control the CD38 until I can get the senescence levels under control)

 

Here is the specific product I ordered:

 

https://donotage.org.../pure-apigenin/

 

Other than Fisetin, Quercetin, Dasatinib (which is very expensive) I have also read on the forums about FOXO4-DRI, but that also seems very expensive, and none of these have any direct trials on SA-β-gal levels as measured in the blood (that I can find).

 

Not really sure what the optimal path forward is.  Oh, I weigh just under 100 kilograms, so I use slightly large amounts of supplements than the average person.

[Florin]

Did your SA-β-gal and NAD levels change after you took the senolytics?

[BrentS]

Did your SA-β-gal and NAD levels change after you took the senolytics?

 

I did the first test on 5 Jul 2021, and I got the results last week.  I am planning to do 3 to 5 cycles of supplements, 6 weeks apart, then do a second test.  The tests are pricey, and I cannot afford to do them monthly, or weekly.

[Kentavr]

Good afternoon!

 

Quercetin can purposefully accumulate in some body tissues, avoiding other body tissues. In order for it to penetrate into all tissues of the body, quercetin in liposomes can be considered.

In addition, it is better absorbed, and for this reason it can be more effective than regular quercetin. Have you considered this option?

Edited by Kentavr, 11 August 2021 - 05:39 PM.

[BrentS]

 

Good afternoon!

 

Quercetin can purposefully accumulate in some body tissues, avoiding other body tissues. In order for it to penetrate into all tissues of the body, quercetin in liposomes can be considered.

In addition, it is better absorbed, and for this reason it can be more effective than regular quercetin. Have you considered this option?

 

 

I considered it yes. but I would not know how to balance the Quercetin and Fisetin if the Quercetin was liposomal.  Right now I can just take equal amounts of both, as capsules, and the cost is not completely prohibitive to take enough that it should be able to push past the liver degrading amounts.  I would have to wait for some studies done on liposomal quercetin to see how the bio-availability compares to the capsule form, and then I would have to work out how much Fisetin to take to balance it.

 

In other news, my Apigenin arrived yesterday.  I took a capsule, 250mg, with supper.  Seemed to have a slight case of diarrhea a few hours afterwards, and then after that felt extremely hungry.  The plan is to take 250mg twice a day, one with breakfast and one with supper, but can't do that if diarrhea will be a problem.  Will try for a few days and see if my body can adapt to it.

[BrentS]

Update on cycle 2:

 

20 Aug 2021 - took 3g each of Fisetin and Quercetin, swallowed them with a glass of olive oil.  Had a mild headache afterwards, so went to bed early.  Next morning, urine had a strong smell.

21 Aug 2021 - took 3g each of Fisetin and Quercetin, swallowed them with a glass of olive oil.  No headache today or urine smell, perhaps yesterday was an anomaly?

22 Aug 2021 - took 4g each of Fisetin and Quercetin, swallowed them with a glass of olive oil.

23 Aug 2021 - took 4g each of Fisetin and Quercetin, swallowed them with a glass of olive oil.

24 Aug 2021 - took 5g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

 

Used EMI brand olive oil, more expensive but the taste is not as strong.  Total olive oil used this time was just over 1L.  I was going to increase the amount of supplements by 1g each per day, but I decided after the headache on the first day to repeat that same amount.  When i didn't get the headache again then i increased on day 3 and again on day 5.

 

I am wondering if a better protocol might be to do 1 day every 2 weeks (or even 1 day per week) instead of 5 days every 6 weeks.  But no data at all exists yet afaik.

 

I am still planning to do 2 more cycles and then blood test senescence level again.

 

To update the above Apigenin post, after the second day I noticed no effects on stools from Apigenin.  It has been a few weeks now, and I have not noticed an energy increase either, but will not know for two more cycles whether the Apigenin is having any effect on plasma NAD levels.

Edited by BrentS, 27 August 2021 - 03:13 AM.

[BrentS]

Update on cycle 3:

 

8 October 2021 - took 5g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

9 October 2021 - took 5g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

10 October 2021 - took 5g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

11 October 2021 - took 5g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

12 October 2021 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

 

In total I used about a liter and a half of EMI brand olive oil this cycle.  At 6g it was taking about an hour and a half to swallow all the capsules.  No headache or any other effects observed this cycle.  I am planning on doing one more cycle in another 7 weeks, then waiting 2 weeks and doing a second blood test to see if it made a difference.

[BrentS]

Update on cycle 4:

 

26 November 2021 - took 7g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.  This cycle I am opening the fisetin capsules and mixing the fisetin powder with the olive oil, still taking Quercetin first in capsule form

27 November 2021 - took 8g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.  Got bad diarrhea, so this appears to be about my limit, so will back down to 6g for the rest of the cycle.  Taking a day off to let my guts settle.

29 November 2021 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

30 November 2021 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

1 December 2021 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.

 

I will have to decide this week whether to do another cycle or get blood tests in another week and a half.  Not certain of optimal path forwards.  The only change I have noticed is my recovery time when working out has decreased from 15 to 20 mins between sets down to 10 to 15 mins between sets, so that is a nice change.  Strength levels are not increasing any faster than before though.

[BrentS]

Update on cycle 5:

 

14 January 022 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil.  This cycle I am again opening the fisetin capsules and mixing the fisetin powder with the olive oil, still taking Quercetin first in capsule form

15 January 022 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil, then decided to add more olive oil, so had another glass (about 500ml total).  Felt slightly queasy afterwards.

16 January 022 - took 6g each of Fisetin and Quercetin, swallowed them with a slightly more than a glass of olive oil, then had another glass (about 500ml total).  Felt very queasy afterwards, and couldn't sleep and threw up 6 hours later.  So too much olive oil bad.

18 January 022 - took 3g each of Fisetin and Quercetin, swallowed them with a slightly more than half a glass of olive oil.  I skipped a day after getting sick from too much olive oil to let my stomach recover.

19 January 022 - took 3g each of Fisetin and Quercetin, swallowed them with a slightly more than half a glass of olive oil.

 

After completing cycle 5, I waited almost 2 weeks, then on 31 Jan 2022 I did a second bloodtest and sent it in to Jinfiniti again.

 

Results were FAR better than expected.  My senescence-associated beta-galactosidase levels dropped from 2190 all the way down to 325!!

 

 

I am going to continue the 5 days on 6 weeks off for the foreseeable future, as I will see over the next few months whether or not some of my problems lessen or disappear with the reduction of senescent cells.  But to maintain I will only be doing 3g per day each of Fisetin and Quercetin.

 

Edit -  one of the vials I sent had problems, so they were unable to test my circulating NAD levels. which I would guess are improved, but still not where I need them to be.  Next time I will wrap the vials in a paper towel before putting them into the ice pack to see if that helps.  Will be several months until next test though.

Attached Files

•  SABgal.jpg   219.47KB   1 downloads

Edited by BrentS, 20 February 2022 - 01:56 PM.

[BrentS]

To add the math from the other person's thread, it appears that on average, each cycle removed approximately 31.7% of remaining SA-B-gal senescent cells:

 

Beginning 2190

Cycle 1    1496

Cycle 2     1021

Cycle 3     698

Cycle 4    476

Cycle 5   325

 

Numbers are not completely accurate because I was playing with doses to see how much my body could handle, but should be a close enough baseline.

[Phoebus]

wow, super interesting, thanks for posting all this 

 

How did you decide on the 5 day/6 weeks cycle? Most people I see are doing 1 or 2 days/month. Also why so much olive oil? That seems like quite a bit of fat. Is the olive oil for absorption? I know that oleic acid temporarily opens up the BBB, so the olive oil might help getting these senolytics into the brain. 

 

How old are you? Have you noticed any visual effects such as less gray hair or fewer wrinkles or anything like that? Seems like you have not noticed any dramatic affects of this therapy as of now. 

[BrentS]

wow, super interesting, thanks for posting all this 

 

How did you decide on the 5 day/6 weeks cycle? Most people I see are doing 1 or 2 days/month. Also why so much olive oil? That seems like quite a bit of fat. Is the olive oil for absorption? I know that oleic acid temporarily opens up the BBB, so the olive oil might help getting these senolytics into the brain. 

 

How old are you? Have you noticed any visual effects such as less gray hair or fewer wrinkles or anything like that? Seems like you have not noticed any dramatic affects of this therapy as of now. 

 

I was trying to figure out a cycle that would not interfere with my gym time.  My gym has been 6 weeks on one week off for years now. I was worried that if the side effects of killing off senescent cells would made me sick I did not want to have that affect my workout days.  Most of the trials are 28 days off 2 days on, so I decided I would do more days on and more days off in a row.  Also I am a bit over 200 pounds so bigger than the average human in most of the trials, so normally that means I need more of a given supplement to get the same effect, but again I was worried about side effects, so I added a 5th day instead of doing more dose for 4 days.  Maybe not a perfect plan, but I felt it would give me the best chance of seeing the effects I wanted without the side effects interfering with workout days.

 

As for the olive oil, the first few cycles I was taking capsules, and every capsule has to be swallowed with liquid, and I read that water interferes with absorption, so I waited 3 hours after I ate, then took a sip of olive oil to wash down every capsule.  At 100mg per capsule when I was up to 60 capsules that is a lot of sips of olive oil.  After consuming the F and Q I then waited another 3 hours before consuming other food or liquid, again to ensure water did not interfere with absorption.

 

I ended up with side effects on some of the days anyways just because I was pushing the doses too see what my body could handle, but it worked out well enough.

 

Chronologically, I turned 50 years old during this set of cycles.  By telomere length I am as old as mid 90s (as low as 4900 base pairs).  I have also sent in another telomere test, but I think that Q and F are just blocking the expression of senescence, I do not think they will fix my telomoere problem, but we will see when I get the results.

 

My hair is still fully grey.  I hypothesize that the greyness is an expression of telomere length, and not senescence, but we will see if there is a change in the color over the next few months.  My micronutrition is pretty spot on, so I have not had any wrinkles to speak of to begin with.

 

I have over the past month noticed less joint stiffness, that that is a feeling and feelings are subjective.  We'll see what happens over the next 6 months or so regarding other side effects.

[BrentS]

Ok, I ran a spreadsheet, and this time I started by calculating the total grams each of F and Q taken, which was 111g total.  Subtracting the before and after numbers gives us a change of 1865 points, which is 16.8 points per gram of each consumed.  So then I built the chart showing the theoretical SA-B-gal values during the experiment. 

 

These numbers are quite different from my first calculation, but I think this table is more realistic, as it accounts for the amounts consumed on each day.

 

Edit - I pasted in a spreadsheet but it displayed improperly upon pressing Post, so I deleted it and screenshotted the spreadsheet and pasted that instead:

 

Attached Files

•  SABgal by day.jpg   100.89KB   1 downloads

Edited by BrentS, 21 February 2022 - 02:42 AM.

[CynthesisToday]

Thank you for sharing the work and data from your protocol so far. It is very thought-provoking.

 

I looked over the Jinfiniti test suite called AgingSOS. Is the "best" set of measurements the one you used? If so, that suite includes a coincident measure of hs-CRP. Did the measured hs-CRP change before and after your protocol series? As I understand it, the protocol is purported to stimulate apoptosis of senescent cells. Apoptosis is supposed to be tightly coupled with efferocytosis in order to prevent, among other things, inflammation. Any thoughts on things you might be doing to help efferocytosis keep up with apoptosis? Are you doing anything in particular to enhance inflammation resolution not mentioned in the protocol documented here? This might include a lower omega-6:omega-3 ratio and use of low-dose aspirin. The considerable EVOO that is part of the protocol might/would be a source of anti-inflammatory compounds if it was unfiltered.

[BrentS]

Thank you for sharing the work and data from your protocol so far. It is very thought-provoking.

 

I looked over the Jinfiniti test suite called AgingSOS. Is the "best" set of measurements the one you used? If so, that suite includes a coincident measure of hs-CRP. Did the measured hs-CRP change before and after your protocol series? As I understand it, the protocol is purported to stimulate apoptosis of senescent cells. Apoptosis is supposed to be tightly coupled with efferocytosis in order to prevent, among other things, inflammation. Any thoughts on things you might be doing to help efferocytosis keep up with apoptosis? Are you doing anything in particular to enhance inflammation resolution not mentioned in the protocol documented here? This might include a lower omega-6:omega-3 ratio and use of low-dose aspirin. The considerable EVOO that is part of the protocol might/would be a source of anti-inflammatory compounds if it was unfiltered.

 

No, the expensive test was too pricey for me, all I got so far was three copies of the cheapest one, which measures SA-B-gal and Intra cellular NAD and circulating NAD. 

 

Other than above protocol I am taking a very large amount of supplements, vitamins and minerals, but I have been for the past decade, and they did not seem to do anything to stop my cells from going senescent or clearing the senescence, whereas the protocol I listed here has made a significant measurable difference, at least in SA-B-gal levels.  Hopefully I will receive the telomere test results this week and make further plans once those are in hand.

 

My omega3 and 6 levels are likely close, I have been taking a tablespoon of flax oil a day for the past 5ish years and a year or so ago I added a tablespoon of avocado oil to balance the 3s and 6s.  Last time I measured was abo0ut 2 years ago and I was higher in 3s, which is when I added evening primrose oil, which was hard to source, and after a year on that I switched it out to the avocado oil. 

 

As far as inflammation specific supplements I also take capsules of turmeric daily and use more as food flavoring.

Edited by BrentS, 21 February 2022 - 02:40 PM.

[BrentS]

This week I received VERY interesting blood results.  To start, here is the results from the Telomere length test I did in 2019:

 Telomere result 27 May 2019.jpg   57.88KB   0 downloads

 

From this result, here is a blowup of the worst telomere type, the granulocyte, which is 1100 base pairs below where it should be for a person of my age.  I have drawn a straight line from my result across to the average green line for all ages, which puts my biological age at approximately 89 years old

:

 Telomere Granulocyte Biological Age approx 89.jpg   49.85KB   0 downloads

 

Exactly 1 year later I repeated the test and the result was very similar.  Some of the telomeres were slightly higher or lower, and I emailed the company that did it and they said the accuracy is +/- 200 base pairs, so if you consider the results they are all exactly the same within the margin of error:

 

 Telomere result 27 May 2020.jpg   60.14KB   0 downloads

 

I was going to wait 3 or 5 years before testing again, as telomere length changes slowly and I wanted to see a result outside the margin of error; but I decided to test again sooner to see if the senescence reduction protocol had made a difference, and to my surprise, the difference was significant:  The Granulocyte and Memory T cell telomeres increased a LOT in length, the B cell telomeres had a slight increase.  The rest were unchanged, or within the margin or error:

 

 Telomere result 31 Jan 2022.jpg   58.09KB   0 downloads

 

To expand on the above result, here is a blowup of the latest granulocyte, which by drawing the line across again has improved my biological age from formerly 89 all the way down to 80, a decrease of 9 years!

 

 Telomere Granulocyte Biological Age approx 80 after Q+F.jpg   50.36KB   0 downloads

 

I do not understand why the Q+F affected some types of telomeres, but not all of them.  Also, now I am not sure what my path forward should be.  My cellular senescence has decreased to where my body can heal itself again, but I would like to get my biological age to be decreased all the way down to match my chronological age.

 

I am going to put a link to this post in the LongeCity telomere subforum, as I would like advice from members that have experimented in that area

 

[Kentavr]

I think the answer is simple: the test shows the average length of telomeres. With senolytics, you destroyed the cells with the shortest telomeres.

By the way, perhaps in this way it is possible to understand which type of cells are affected by Q + F - those cells that showed the greatest average elongation of telomeres.

[CynthesisToday]

Great to see the change in telomere length after your Q+F+EVOO protocol even if it is just in a few of the cell sub-types. Your data sharing continues to be a source of mechanism pondering. Thanks.

 

While reading through other avenues regarding senescence, apoptosis and efferocytosis, I found two articles with possible relevance to this Q+F+EVOO protocol. Specifically, the findings by two separate research groups that components of olive oil decrease levels of measured SA-β-gal:

 

doi:10.3390/ijms18112275 "Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols" (2017)

 

https://doi.org/10.1...1702-018-0031-x "Anti-inflammatory and anti-aging effects of hydroxytyrosol on human dermal fibroblasts (HDFs)" (2018)

 

This paper describes up to 300mg/kg of phenols in EVOO. The density of EVOO is 0.9g/ml. Hydroxytyrosol can be about 30% of the phenol content. There are many other phenols and other potential biology modulating compounds in EVOO. Synergistic effects are also likely including synergism with the Q+F.

 

http://dx.doi.org/10...hem.2012.05.005 " Assay of tyrosol and hydroxytyrosol in olive oil by tandem mass spectrometry and isotope dilution method" (2011)

 

There is a _lot_ of EVOO in this protocol. EVOO* as a source of senolytic or synergistic compounds will definitely need consideration in mechanisms. Reading through the descriptions of each day of protocol, it seems that every ~6g each of Q+F was usually accompanied by about 250ml of EVOO except the January set which had about 125ml of EVOO per day. Sometimes 500ml of EVOO was consumed with the Q+F.

 

The quantity of EVOO consumed will help with absorption via the lymphatic system thus bypassing the liver first pass. There is evidence that high oil intake will increase transport through the portal process, too. 

 

Perhaps a Q+F+EVOO mayonnaise might make it easier to take using less total oil. This might help reduce transport via the portal vein and more in the lymph transport mechanism. Food engineers have been experimenting with using phenols in mayonnaise to help prevent oil oxidation in shelf life. They've shown that a phenol mayonnaise does "dissolve" the phenol effectively as measured by no residual silt. They are currently adjusting levels for palatability. This protocol doesn't seem to be so concerned with taste as with getting the total Q+F loaded.

 

 

* Assuming the EVOO is in fact extra virgin olive oil and not adulterated. Did it meet criteria as defined, for example, here?: 

https://www.epicurio...ive-oil-article

[BrentS]

I think the answer is simple: the test shows the average length of telomeres. With senolytics, you destroyed the cells with the shortest telomeres.

By the way, perhaps in this way it is possible to understand which type of cells are affected by Q + F - those cells that showed the greatest average elongation of telomeres.

 

After considering, I agree with your hypothesis.  And now that the SA-B-gal levels are almost depleted, I would guess the most senescent cells have been destroyed; to progress further I will need a different mode of attacking both senescence and short telomere length.

 

Great to see the change in telomere length after your Q+F+EVOO protocol even if it is just in a few of the cell sub-types. Your data sharing continues to be a source of mechanism pondering. Thanks.

 

While reading through other avenues regarding senescence, apoptosis and efferocytosis, I found two articles with possible relevance to this Q+F+EVOO protocol. Specifically, the findings by two separate research groups that components of olive oil decrease levels of measured SA-β-gal:

 

doi:10.3390/ijms18112275 "Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols" (2017)

 

https://doi.org/10.1...1702-018-0031-x "Anti-inflammatory and anti-aging effects of hydroxytyrosol on human dermal fibroblasts (HDFs)" (2018)

 

This paper describes up to 300mg/kg of phenols in EVOO. The density of EVOO is 0.9g/ml. Hydroxytyrosol can be about 30% of the phenol content. There are many other phenols and other potential biology modulating compounds in EVOO. Synergistic effects are also likely including synergism with the Q+F.

 

http://dx.doi.org/10...hem.2012.05.005 " Assay of tyrosol and hydroxytyrosol in olive oil by tandem mass spectrometry and isotope dilution method" (2011)

 

There is a _lot_ of EVOO in this protocol. EVOO* as a source of senolytic or synergistic compounds will definitely need consideration in mechanisms. Reading through the descriptions of each day of protocol, it seems that every ~6g each of Q+F was usually accompanied by about 250ml of EVOO except the January set which had about 125ml of EVOO per day. Sometimes 500ml of EVOO was consumed with the Q+F.

 

The quantity of EVOO consumed will help with absorption via the lymphatic system thus bypassing the liver first pass. There is evidence that high oil intake will increase transport through the portal process, too. 

 

Perhaps a Q+F+EVOO mayonnaise might make it easier to take using less total oil. This might help reduce transport via the portal vein and more in the lymph transport mechanism. Food engineers have been experimenting with using phenols in mayonnaise to help prevent oil oxidation in shelf life. They've shown that a phenol mayonnaise does "dissolve" the phenol effectively as measured by no residual silt. They are currently adjusting levels for palatability. This protocol doesn't seem to be so concerned with taste as with getting the total Q+F loaded.

 

 

* Assuming the EVOO is in fact extra virgin olive oil and not adulterated. Did it meet criteria as defined, for example, here?: 

https://www.epicurio...ive-oil-article

 

Thank you for the study quote on EVOO acting as another mode to decrease senescence, I was taking it just to maximize absorb-ability of the F+Q, I did not realize that EVOO itself had similar useful properties.

 

The specific EVOO I am taking is this one:

 

https://vinaelena.co...cts/aceite-emi/

 

This is a smaller family owned vineyard produced olive oil, it does not appear that they do third party testing, but if you are interested in asking them their contact information is at the top of their webpage.  That said, based on my measured results, I would expect that if  the product was cut with an inferior oil I would have been less likely too see large drop in SA-B-gal; as inferior oils would likely not have worked to the same effect.  But with N=1 this cannot be proven.

 

Fisetin is a pretty strong bitter yet foul taste, vaguely reminiscent of rancid chalk. I do not think that mixing it into mayo would help much. In fact, I would NOT recommend it mixed into EVOO as I did if you have a choice.  If I had to do this again, I would have purchased the slightly more expensive per mg capsules from https://donotage.org...s/pure-fisetin/, because their capsules are 400mg, so instead of 60+ capsules I would have only had to take 15ish, which is FAR more reasonable.  I did it this way because it was cheaper and I was willing to deal with the bad taste for a few days every few months in exchange for some hope of a positive resolution to my senescence issues.

[Kentavr]

After considering, I agree with your hypothesis.  And now that the SA-B-gal levels are almost depleted, I would guess the most senescent cells have been destroyed; to progress further I will need a different mode of attacking both senescence and short telomere length.

 

 

I have previously made a suggestion on this topic.

If you use "Q and F" in liposomes, you can destroy senescent cells in those places where "Q and F" are not sent by the body.

 

Liposomes mask biologically active substances and even make it possible to overcome the blood-brain barrier.

 

As for the dosage, I can not advise you.

 

1. On the one hand, lipomas greatly improve the bioavailability of water-insoluble components that are not capable of emulsification.

 

2. On the other hand, active components, being distributed more evenly throughout the body, will not accumulate only in some tissues, but will be more evenly distributed in organs and tissues. As a result, each of the components may seem smaller when converted to one cell.

 

For this reason, I advise you to conduct an experiment with further analyzes. This will help the community a lot.

[CynthesisToday]

I found the papers through the ebook "Redox Signaling and Biomarkers in Ageing", (2022), chapter 12: 

https://www.research...ok.pdf#page=265

 

Chapter 12. "Senolytic Phytocompounds in Redox Signaling", Table 12.1 "List of compounds targeting senescence" lists references. The "Remarks" column of this table summarizes the biomarkers such as SA-β-gal that were affected (or not).

 

btw, I tested the mayonnaise method for enhancing uptake of Q+F. My mayo preference is Kewpie mayonnaise I purchase from a Japanese market. It contains 4 egg yolks per 500g canola oil/vinegar so it has a high capacity to take on additional oil and phenols yet maintain emulsion strength. Whisking two tbsp of Kewpie, 1 tbsp sesame oil and 1.5g each of quercetin and fisetin produced a strong emulsion with little feel of grit. Allowed the new emulsion to meld for at least 30min first. The choice of additional oil as sesame was based on research measuring portal vs lymph partitioning of lipids based on oil type infused to the duodenum of rats. My personal taste finds Kewpie mayo very tart and savory. Two observations based on my personal taste were: Kewpie tartness was stronger than the alteration in overall flavor (but notably altered) and the strength of the emulsion prevented penetration of the tongue mucus such that I could swallow small spoonfuls without overwhelming my tastebuds. Of course, everyone's sense of taste is different. I took small spoonfuls over a two hour interval to hypothetically keep from overwhelming the lymph transport system, thus partitioning more to portal, and allow furthering melding of phenols into the emulsion.

 

doi: 10.1152/ajpgi.1991.261.3.G530 "Portal transport of absorbed lipids in rats" (1991)

 

scholar.google search terms "phenols mayonnaise" for food research on incorporation of phenols in mayonnaise.

Edited by CynthesisToday, 28 February 2022 - 04:59 PM.

[QuestforLife]

This week I received VERY interesting blood results.  To start, here is the results from the Telomere length test I did in 2019:

Telomere result 27 May 2019.jpg

 

From this result, here is a blowup of the worst telomere type, the granulocyte, which is 1100 base pairs below where it should be for a person of my age.  I have drawn a straight line from my result across to the average green line for all ages, which puts my biological age at approximately 89 years old

:

Telomere Granulocyte Biological Age approx 89.jpg

 

Exactly 1 year later I repeated the test and the result was very similar.  Some of the telomeres were slightly higher or lower, and I emailed the company that did it and they said the accuracy is +/- 200 base pairs, so if you consider the results they are all exactly the same within the margin of error:

 

Telomere result 27 May 2020.jpg

 

I was going to wait 3 or 5 years before testing again, as telomere length changes slowly and I wanted to see a result outside the margin of error; but I decided to test again sooner to see if the senescence reduction protocol had made a difference, and to my surprise, the difference was significant:  The Granulocyte and Memory T cell telomeres increased a LOT in length, the B cell telomeres had a slight increase.  The rest were unchanged, or within the margin or error:

 

Telomere result 31 Jan 2022.jpg

 

To expand on the above result, here is a blowup of the latest granulocyte, which by drawing the line across again has improved my biological age from formerly 89 all the way down to 80, a decrease of 9 years!

 

Telomere Granulocyte Biological Age approx 80 after Q+F.jpg

 

I do not understand why the Q+F affected some types of telomeres, but not all of them.  Also, now I am not sure what my path forward should be.  My cellular senescence has decreased to where my body can heal itself again, but I would like to get my biological age to be decreased all the way down to match my chronological age.

 

I am going to put a link to this post in the LongeCity telomere subforum, as I would like advice from members that have experimented in that area

 

Thank you for sharing your results.

 

May I ask where you got your telomeres measured? 

 

I have used LifeLength several times in the past to measure the effect of various supplements on my telomere length, but unfortunately they no longer accept blood samples from the UK due to the extra customs checking time required since Brexit.

 

The telomere length difference between granulocytes and their myeloid progenitor is about 500bp compared to 1000bp between lymphocytes and myeloid progenitors. This is because lymphocytes divide many more times. See https://www.ahajourn...baha.107.160846

 

I suggest that in destroying cells with senolytics your myeloid progenitors have been forced to regenerate your pool of immune cells. This is more noticeable in the telomere lengths of those cells that have divided less times from the progenitor stage. 

[BrentS]

I found the papers through the ebook "Redox Signaling and Biomarkers in Ageing", (2022), chapter 12: 

https://www.research...ok.pdf#page=265

 

Chapter 12. "Senolytic Phytocompounds in Redox Signaling", Table 12.1 "List of compounds targeting senescence" lists references. The "Remarks" column of this table summarizes the biomarkers such as SA-β-gal that were affected (or not).

 

btw, I tested the mayonnaise method for enhancing uptake of Q+F. My mayo preference is Kewpie mayonnaise I purchase from a Japanese market. It contains 4 egg yolks per 500g canola oil/vinegar so it has a high capacity to take on additional oil and phenols yet maintain emulsion strength. Whisking two tbsp of Kewpie, 1 tbsp sesame oil and 1.5g each of quercetin and fisetin produced a strong emulsion with little feel of grit. Allowed the new emulsion to meld for at least 30min first. The choice of additional oil as sesame was based on research measuring portal vs lymph partitioning of lipids based on oil type infused to the duodenum of rats. My personal taste finds Kewpie mayo very tart and savory. Two observations based on my personal taste were: Kewpie tartness was stronger than the alteration in overall flavor (but notably altered) and the strength of the emulsion prevented penetration of the tongue mucus such that I could swallow small spoonfuls without overwhelming my tastebuds. Of course, everyone's sense of taste is different. I took small spoonfuls over a two hour interval to hypothetically keep from overwhelming the lymph transport system, thus partitioning more to portal, and allow furthering melding of phenols into the emulsion.

 

doi: 10.1152/ajpgi.1991.261.3.G530 "Portal transport of absorbed lipids in rats" (1991)

 

scholar.google search terms "phenols mayonnaise" for food research on incorporation of phenols in mayonnaise.

 

I downloaded, the book you linked, but that is 450ish pages, and will take me a while to read.  I did look at the table, and I am also taking Melatonin, 3mg a day, and have been doing so for about 5 years, so that did not seem to have an effect, other than allowing better sleep.
 

[BrentS]

Thank you for sharing your results.

 

May I ask where you got your telomeres measured? 

 

I have used LifeLength several times in the past to measure the effect of various supplements on my telomere length, but unfortunately they no longer accept blood samples from the UK due to the extra customs checking time required since Brexit.

 

The telomere length difference between granulocytes and their myeloid progenitor is about 500bp compared to 1000bp between lymphocytes and myeloid progenitors. This is because lymphocytes divide many more times. See https://www.ahajourn...baha.107.160846

 

I suggest that in destroying cells with senolytics your myeloid progenitors have been forced to regenerate your pool of immune cells. This is more noticeable in the telomere lengths of those cells that have divided less times from the progenitor stage. 

 

https://repeatdx.com/

 

This is a Canadian company; the good telomere test is $800 USD, and it has to be ordered by a Medical professional.  It take them ~3 weeks to process the sample after it arrives, and they then release the results only to the medical professional.  But the best telomere length test I could find

[s1lordi]

Seems that stemcell remains the longest part, which means merely targeting SRF, SASP and DAMP would be enough to keep them youthful.

[Kentavr]

Seems that stemcell remains the longest part, which means merely targeting SRF, SASP and DAMP would be enough to keep them youthful.

 

No. I think removing SASP won't be enough. It will also be necessary to remove the aging proteins that Irina Konboy spoke about in her recent report.

Additionally, you will need to increase the elasticity of the extracellular matrix so that the aging programs are not activated by squeezing the extracellular matrix.

 

So, 3 main things:

 

1. Proteins.

2. Aging cells / immunity.

3. Extracellular matrix.

 

These are the main reasons. The rest is easier to fix.

Edited by Kentavr, 11 March 2022 - 06:43 PM.

[johnhemming]

If we look at the issue of histone acetylation failing simply blocking Interleukin-10 may do, but it is also likely to have side effects.  I am currently trying supplementing with citrate as an alternative.

[ambivalent]

Any update, Brent?  

[ironfistx]

Interested

[BrentS]

I decided a year ago that my next step was to begin a hyperbaric oxygen protocol. Due to the cost of private sessions, I decided to buy a personal chamber for my house. Trying to buy a chamber and implement this has been a complete CF.  A year ago used chambers were selling for between 5 and 15k USD, and I had placed a bid on one for 20k that had years and usable hours left on the glass.  Then someone helpfully did a study showing that hyperbaric O2 can help with long haul covid symptoms, and when that was released the price of used chambers doubled overnight, and I was unable to acquire one.  I have been waiting and watching for almost a year now for the prices to go back down. 

 

When I can buy a chamber and begin that protocol, I will do another set of blood tests right before I begin.  I have been continuing Q+F for the past year, but at a lower dose (mostly for maintenance) so I am expecting a slight to no reduction in the senescence levels.

 

At the current rate, it will be months to a year before I have the pieces in place to continue.