Did anyone detect a change in their CRP levels after doing the protocol?
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It’s possible if you modulate the efficiency of the energy system. For example, In the early 1930s, the chemical uncoupling agent 2,4-dinitrophenol (DNP) was promoted for the very first time as a powerful and effective weight loss pill but quickly withdrawn from the market due to its lack of tissue-selectivity with resulting dangerous side effects, including hyperthermia and death.
My follow up AgingSOS after 22 days on 50% DAV (Jan 15) vs baseline from Oct 17, 2023 were mixed:
Beta-Galactosidase: 1235 (increased from 853 on Oct 17). NOTE: While this indicates worse SASP inflammation, the difference is not really that large: Optimal range is 0-750, Sub-Optimal 750-1500, Abnormal 1500-2500, Very Abnormal 2500-6000
Interleukin 1-beta : 0.0 pg/mL (unchanged)
Interleukin 6 : 1.1 pg/mL (down from 4.4 pg/mL on Oct 17, normal is < 3.0)
Interleukin 8 : 82.2 pg/mL (up from 30 pg/mL on Oct 17, normal is < 20))
Tumor necrosis factor alpha: 9.2 pg/mL (down from 12.7pg/mL on Oct 17, normal is < 12.0)
Intracellular NAD : 105.9 uM (up from 65.1 uM on Oct 17, optimal range 40-100)
Note that Interleukin factors and Tumor necrosis factor alpha can reflect both SASP inflammation (Senescence) as well as acute inflammation from infections, so are less reliable individually than Beta-Galactosidase, which is supposed to depend only on SASP inflammation.
Intracellar NAD is not directly related to Senescence, but high levels of Senescent cells will increase systemic inflammation which in turn will result in higher use (and depletion) of NAD resulting in lower NAD levels, given similar levels of NAD synthesis or supplementation. My levels above reflected the same level of NAD supplementation on both dates of 500mg Lipo NMN and 600mg Lipo NR per day so the increase from 65.1 to 105.9 is quite large and significant. Jinfinity warns that values over 100 may be counterproductive since this may energize senescent cells, increasing their production of SASP. On the other hand one possible explanation for the increase in NAD is that a significant fraction of senescent cells were killed off, raising the levels of NAD in all body cells (including the blood cells being measured), but the rise in NAD levels in the remaining senescent cells MAY be sufficient to raise the levels of some SASP chemical emitted by senescent cells. The other possibility is that my 50% DAV was ineffective in lowering SASP and the change in NAD is unrelated to the DAV, but the change in NAD levels is so much larger than the increase from using Fisetin (In another thread I used 1500mg/day Lipo Fisetin for 3 days, which raised my NAD levels from 24.3 uM to 28.1 uM, without supplementation of NAD precursors) that it seems more likely that even 50% DAV is a much stronger Senolytic than Fisetin.
To verify my hypothesis, I intend to reduce my NAD supplementation to 250mg Lipo MNN + 300mg Lipo NR per day for 6 weeks and retest just intracellular NAD (repeating if needed) until it is below 50 uM. Then I plan to repeat a full 5 week DAV protocol and see if that raises NAD without raising SASP levels (particularly Beta-Galactosidase).
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I would like to put my foot in the conversation once again, despite my limited typing skills. I must say I appreciate your enthusiasm for learning and thereby keeping the conversation alive. I believe you to be quite correct that the effects of the study are more important than a discussion of the best dosage parameters of vit C. Concerning the discussion I would like to make the following observations:
1 Human biochemistry is a very complicated subject marked by mounds of enzymatic reactions and manipulated by genetic expressions (the abbreviations of which would fill a text book).
2 biochemical individuality is equally complicated (if it weren’t the doctor’s job would be easy cause everyone would be the same and they would already know what works).
3 Anyone who thinks he understands any reaction in everyone need only peruse the peer reviewed journals for the sheer volume of new discoveries, for a lesson in humility. So we are therefore left with clinical trials to provide some insight into the human condition.
4 In our case this means experimentation…but the one thing missing, is always some method of validating our efforts. Some way of knowing we are doing any good. Ideally, we would have a home kit for measuring the die-off products of senescent cells, and only those (which may not be as crazy as it sounds considering test kits for blood sugar and cholesterol). Barring that we are left with our own perception of how we feel.
You see it does not make a hill of beans what forest of biochemical theory we choose to wander in as long as it does not prevent us from making progress. Such is the life of an experimenter. I therefore offer the following possible milestones of success for consideration:
1 apon dosing oneself with senolytics look for a minor flu-like response of dead cellular debris dumped into the blood stream. (headache, fatigue, muscle ache, and mild temperature rise all qualify). My wife and I have experienced these in our trials of DAV, dacatinib/quercitin, and fisetin. (If yours are more than your wife you may have more senescent cells).
2 The data shown by desertshores points out one factor for consideration namely that triple therapy after pretreatment is considerably less effective than NO pretreatment. This looks very much like a tolerance issue. The liver will gradually send out more soldiers to “nullify” a constant “incursion of foreign invaders” across the digestive boundary in a process called “first-pass” metabolism. This process is apparently avoided in other “hit and run” senolytic self-experiments like dasatinib/quercetin and fisetin that run for 3 days only. Some have even adopted strategies of aiding blood concentrations with grapefruit juice or bioperine (pepper extract). So what of our DAV trials? I believe it possible that the author took a standard dose of doxycycline for a prostrate problem (common in men) and added in the azith. and vit C as a concomitant experiment (with a lifetime of experience) to see what would occur. This would explain the somewhat exaggerated dose of doxy (appropriate for bacterial prostatitis but not for a senolytic experiment). I therefore think the appropriate dose of doxy to be half of his patent discussion with a length and repetition for most effective outcome to be detirmined.
3 one more issue about Vit C… There are other pro-oxidents. Tylenol is said to be one, which is why it is dangerous to the liver (in large doses with alcohol). There are others of course, but safety would dictate you stay with the pros ( like Lisanti) who have a lifetime of experience, which puts the load squarely on his shoulders, which is why he will never encourage self-experimentation, which puts the load squarely on your shoulders where it belongs. So I say again: check for sensitivity first by nibbling, then a little more til your sure of no reaction…then time off to remove tolerance, and finally the experiment.
4 finally there are other approaches that might not kill you…penetrants.
DMSO, a solvent for most water-insoluable phytosterols such as fisetin and quercetin, but if you use this with any contaminant on your skin you are asking for trouble. So be carefull out there, its a brave new world.
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Oh and one last thing,I know sometimes it feels like you are not getting anywhere but consider: if the secret to life extension were simple, someone would have discovered it already. In truth the annals of science (Physics as well as Biochemistry) are filled with new discovery by accident… sometimes it takes just that last step to make everything fall into place. This is a new field with a new language to learn so educate yourselves, use google scholar to look up articles of interest to you and read the abstract summaries, the vocabulary haze will begin to lift and you will discover just how much is out there. As an example, doctors are now treating cystic fibrosis with low dose Azithromycin and their lungs are getting better instead of Increasing scar tissue to the point of death. They have been so successful, that clinical trials for treatment of COPD have begun and look promising! To my mind, this is evidence of clearing senescent cells, removing SASP inflammation, and allowing the healing process to proceed. This is exactly what we are trying to do to the senescent cells in our bodies! There is also a biotech company that has demonstrated that one injection has removed inflamation, encouraged healing on the macular floor, and improved vision considerably in Advanced Macular Degeneration, a previously incurable disease; and this improvement has remained throughout the second phases (a+b) of the clinical trial without any further shots. The evidence is out there people, don’t give up, the treatment is only the first step, now let the healing begin. As I said in my first blog, It took a long time to get this way, it will take some time to get back.
One more aside: Do not use diphenhydramine (dph). It is common in allegry and sleep medications since the 1960’s. They never looked at long term studies till about 5 years ago. There is a horrible study that shows a 64% increase in strokes in those who use it more than 14 days a month, and nearly as bad with less than 14 days. This is the worst result I have seen in all my studies over 40 years. Luckily, more modern drugs are better researched and even followed after approval for any problems. Use something else! If you kill the patient, you ruin the experiment. Or if you don’t heed this warning, please don’t procreate.
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That was me too! No change whatsoever-
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FWIW
N=1
Went for a hair cut last night (03/04/2024)
the person that cuts my hair states out of nowhere the lower back of you hair is black.
It was not black last time she cut my hair before. My hair is gray and black more gray than black
The only change I have done is this DAV Therapy as I posted dates above, approximately 5 ½ months ago.
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Well with all due respect there is few variables in your post. 1. your hair decided to get dark only in lower back of your head. 2. you needed someone else to tell you that you hair was turning dark. sorry man, not buying it. If you yourself couldn’t see a difference in your hair elsewhere, then your hair was exactly like that even pre your DAV. Not to be rude or argue, but just to note the fact that we (all) get carried away sometimes when we try something, and we really want it to work lol
I have nothing to prove to you or anyone else.
The person who normally cut my hair made the statement
I do not care if it is black or gray.
I will be doing the DAV Therapy on a much tighter schedule.
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Let us know if you feel any benefits.
Thank you for sharing. As you know I was part of the initial ‘DAV-onauts’ at the end of '23. Hoping to see some good results too (I think some hair has grown back, which I know is controlled by senescence). Will also be repeating the DAV protocol annually (at first - tempted to do it every 6 months).
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I am planning another 5 week course, as soon as I get the prescription refilled {this week 03/05/2024]
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Did you discuss any of your longevity efforts with her in the past? Just curious if she’s bringing this up completely independent of any past discussions that may have been about longevity, anti-aging, etc…
I’ve been on rapamycin just short of 2 years. It definitely does not cause weight loss for me. I have some belly fat and was looking forward to see progress there but it hasn’t changed at all. Just the way it is.
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Same here, I have not lost one single pound while on Rapa (over a year on it)
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Rapamycin, originally developed as an immunosuppressant for preventing organ rejection in transplant patients, has unexpectedly become a subject of interest in the realm of weight management. Let’s delve into its fascinating properties and explore how it might impact weight loss:
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Enhanced Metabolism: Rapamycin acts through the mechanistic target of the rapamycin pathway within cells. This central regulator influences protein synthesis, energy metabolism, and autophagy. One of the significant rapamycin weight loss benefits is its ability to raise insulin sensitivity. By doing so, it helps control blood sugar levels and reduces insulin resistance. Stable blood sugar levels can prevent hunger and cravings for high-calorie, sugary foods, which is crucial for weight management¹.
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Appetite Regulation: Sensitivity to insulin is closely tied to appetite regulation. When blood sugar levels remain stable due to improved insulin sensitivity, it can help lower cravings and prevent overeating. Effective use of rapamycin may contribute to maintaining metabolic health and achieving a normal weight¹.
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Visceral Fat Reduction: While rapamycin itself doesn’t directly stimulate weight loss, it appears to make weight loss, particularly visceral fat reduction, easier when combined with a healthy diet and exercise program⁴.
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Animal Experiments: In animal experiments, rapamycin demonstrated improved weight loss even on a high-fat diet. By inhibiting mTOR (a protein controlling cellular development and metabolism), rapamycin encourages fat burning over storage³.
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Leptin Regulation: Rapamycin affects how the body produces leptin, a hormone produced by fat cells that influences hunger and metabolism. In older rats (equivalent to 65-year-old humans), body weight dropped by approximately 13 percent after rapamycin treatment².
In summary, while rapamycin isn’t a magic weight loss pill, its multifaceted impact on cellular processes and metabolism makes it an intriguing candidate for further research in weight management. As always, consult your doctor before making any health-related decisions¹.
Source: Conversation with Bing, 4/10/2024
(1) Exploring the Potential of Rapamycin for Weight Loss: A Comprehensive … https://valhallavitality.com/blog/exploring-the-potential-of-rapamycin-for-weight-loss-a-comprehensive-review.
(2) Rapamycin and Visceral Fat Reduction. Rapamycin and Visceral Fat Reduction.
(3) Harmony of Health: Unveiling the Rapamycin for Effortless Weight Loss. https://baltimorepostexaminer.com/harmony-of-health-unveiling-the-rapamycin-for-effortless-weight-loss/2024/01/25.
(4) Existing drug used in transplants causes older rats to lose weight … Existing drug used in transplants causes older rats to lose weight - News - University of Florida.
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It might be me, but i have lost absolutely nothing on RAPA(all being equal), but I am the type that has it really hard to lose weight. The only way I lose weight is if I do protein only food for a certain period of time, or if I fast for more than two days-then my fat melts away very fast.
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Yes, in humans there has not been much weight loss, if any, in clinical studies.
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I have started telmisartan to get my blood pressure in the optimal range (didn’t have high blood pressure). Its been really effective with the BP but have also noted visceral fat melting away.
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FWIW
Started{04-14-2024) the 2nd round of DAV Therapy, using the same dosing/procedure as before.
Six day’s only noticed the same as before, less knee joint pain.
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