CD38 gets in the way of NR and NMN for increasing NAD+
Вставка
- Опубліковано 8 лип 2024
- Join us on Patreon! / michaellustgartenphd
Discount Links:
NAD+ Quantification: www.jinfiniti.com/intracellul...
Use Code: ConquerAging At Checkout
Green Tea: www.ochaandco.com/?ref=conque...
Oral Microbiome: www.bristlehealth.com/?ref=mi...
Epigenetic Testing: Trudiagnostic.pxf.io/R55XDv
Use Code: CONQUERAGING
At-Home Blood Testing: getquantify.io/mlustgarten
Diet Tracking: shareasale.com/r.cfm?b=139013...
If you'd like to support the channel, you can do that with the website, Buy Me A Coffee:
www.buymeacoffee.com/mlhnrca
Conquer Aging Or Die Trying Merch! my-store-d4e7df.creator-sprin... - Наука та технологія
Thank you! I’ve been supplementing with Quercetin and dried parsley in conjunction with nmn. I’m below 25 BMI and do intermittent fasting. Great video
Dr. Lustgarten is one of the most brilliant, comprehensive, and well spoken of all the antiaging scientists I've heard so far! He's uncovering amazing information!
Thanks for a cogent analysis of the anomalies of NR-NMN supplementation. Well done!
Great information!!!
You gave the best explanation in this era, thank you so much.
Very well explained! Thank - much appreciated...
Thank you for this GREAT VIDEO
Great stuff, novel connections, well presented, as always.
Great investigation and explanation. Thank you!
Thanks Steve!
Very interesting
Thanks for all the serious work you have done. It is my understanding that it is important to first test what your NAD+ level is. If it is not in the optimal range, then supplement with NR or NMN to get it up into the optimal range. Once consistently there, then you can test to see if there is any effect on your rate of aging.
Thanks KristineK, and I agree about testing. In terms of raising NAD, it could also involve Vitamin B6, which I covered in last week's video:
ua-cam.com/video/zqzCMt8YwRo/v-deo.html
So what's the mechanism for quercitin to reduce CD38 and thereby increase NAD+?
So, supplementing with Quercetin should be together with NAM or NR?
And so i do. Plus IF and the carnivore diet.
Just saw your video 1 yr late. Your review and impact of CD38 is very interesting and may answer why some people more when using the supplements. First you have to be healthy with a normal BMI and potentially no other diseases before pursing the longevity strategy.
Thanks ccamire, and I agree. just adding a bit, with "healthy" being defined as regular biomarker tracking, but also including leanness and external fitness.
awesome
Parsley if it’s cool dried it’s the strongest but if it’s heat dried much of it is destroyed so you need to find that out first and buy organic all the time
I eat it fresh, not dried
Presumably if LPS is present in the bloodstream then that's a sign that the gram-negative bacteria are there and the CD38 is being produced by the macrophages as part of the immune response. Therefore maybe it isn't such a good idea to inhibit the CD38 protein and a better approach would be to reduce the gram-negative bacteria in the gut and decrease the gut permeability. One test of that hypothesis is to look at the differences in health between the CD38 Knock Out mice and their Wild Type counterparts. Do they have a greater susceptibility to infection than their WT cousins or do they live shorter lives overall?
I agree with your premise to go after a (or the) potential root cause of increased CD38 expression, LPS, and also have a video about reducing LPS:
ua-cam.com/video/NGrYzOKGBXA/v-deo.html
I haven't seen lifespan data for CD38 KO mice, but I'd bet that they live shorter than WT.
Niacin?
I'd happily have lots of dried parsley but I'm concerned about oxalate levels
Yet another reason not to be obese... good stuff thanx.
*You meant to not be obese, right? The 2 NR studies in obese people didn't work in terms of raising NAD+ levels...
@@conqueragingordietrying1797 Yes, edited.
I feel your info is the most accurate, however, you drive past us at the speed of 200 Mi/h and we barely have a glimpse of your wisdom. The next question for obese people, does supplementation with CD38 suppressing additives help NAD+ levels. Like having, Quercetin, Alpha Lipoic Acid, and or TMG supplement help increase NAD levels in high BMI people?
Your are an intelligent person :)
Thanks H Mandeel! When I come across a video that is fast like mine, I rewatch it until I understand it, that may help!
@@conqueragingordietrying1797 hahaha ... I understood the vid and was teasing you cause your presentation style is associated with highly intelligent people. Love the content and wanted to know if some supplements would supress CD38, if you know.
@@hmandeelful Ha, I have a video for that, too!
ua-cam.com/video/5-2YoGctcCk/v-deo.html
how do you test for endotoxin levels
I haven't seen its commercial availability, but I could be wrong. Alternatively, blood microbiome analysis is possible through Karius (I'm not sponsored by them):
kariusdx.com/
Great video. It makes me wonder if it would be a good idea to do something to kill gram-negative bacteria. Is there a way to kill gram-negative bacteria that is not toxic to human cells? Also, are there any "good" gram-negative bacteria that we want to keep around? And do the immune systems of younger people keep gram-negative bacteria under control?
Thanks James. Gram-negative bacteria make up a significant proportion of our normal gut microbiome. During aging that increase, and gut barrier function decreases, thereby leading to a greater influx of LPS or the actual gram-negative bacteria into the blood. I'll make a video about this at some point.
@@conqueragingordietrying1797 Thanks for the reply. So promoting a profile of gut bacteria like that of younger people and maintaining good gut membrane integrity would be beneficial.
@@jamesf7933 Yep!
Hi, I practice time-restricted eating, my eating window is in the morning. I also take NMN and I figured the best time to take it is in the morning before breaking my fast, since sirtuins expression should be at its peak. I have a couple of questions:
1) Would you take NMN sublingually or would you ingest it?
2) How apart from my breakfast should I take NMN? Right before? 10, 20, 30 minutes before? I have no idea!
Thanks
I can't tell you when the best time would be to take it. A better idea is self-experimentation. Would you expect insulin sensitivity to improve? If so, measuring your blood glucose every morning, fasted, with/without NMN to see if it works could be a good approach.
Michael Lustgarten, Ph.D. Thanks. I was thinking of something else though, that is whether NAD+ required available energy (glucose) to aid in the repairing process, but I don’t think that that is the case.
What about sublingual vs oral?
@@omarino99 Ha, I guess you missed this video about CD38 (ua-cam.com/video/pj-CSSghDXo/v-deo.html).
If CD38 is elevated, it won't matter if NR or NMN is taken below the tongue or swallowed, it will likely be degraded by CD38.
@@conqueragingordietrying1797 I watched a Douglas Wallace lecture where they showed combining low dose of leucine with NR/NMN increased NAD levels and did not activate mTOR.
Would you expect a prolonged fast of 3-7 days + NR to be a more rapid intervention than CR + NR in regards to boosting NAD+?
Further more, are there any studies on longer fasts and LPS?
Ha, I can guess, but the best way to assess that would be blood testing before and after...
Do the CD38KO mice grow old like the WT mice?
Great question. I searched PubMed, and I didn't find anything in terms of survival curves for CD38 KO mice.
How does LPS end up in blood in the first place? And how does ageing and obesity increase its levels?
This video addresses much of that:
ua-cam.com/video/NGrYzOKGBXA/v-deo.html
@@conqueragingordietrying1797ohh. Thank you!
I wonder - as intermittent fasting can mimic some effects of CR - is it known to also affect LPS levels?
No studies have been published for that, but it looks like IF improves outcomes that are induced by LPS:
pubmed.ncbi.nlm.nih.gov/?term=%22intermittent+fasting%22+%22lps%22&sort=date&size=200
a new 6 month study on men has shown major benefits from alternate day fasting ( one of many benefits)
48% caloric reduction
@@stellarblur Thanks Matt. From my experience, it's tough to stick to eating every other day. But if people can do that, great!
I've done low-carb for years. As many have observed, hunger goes down and metabolism goes up. Many find themselves naturally drawn to fasting or even unintentional caloric restriction. I do some intermittent fasting, almost OMAD, on work days.
On those days, I often try to eat as many calories I can stuff in my gullet in a short period of time, combined with lots of fat. But even then, my calorie intake might be relatively lower. I'm sure I often end up doing caloric restriction in practice.
I do 5:2 and find it quite doable
What is LPS ?
For more info on LPS, see 1:27 of this video:
ua-cam.com/video/NGrYzOKGBXA/v-deo.html
so is rapamycin lowering gram negative bacteria?
is that why, short term use seems to increase longevity.
also is the lower amount of LPs in young blood the reason
young blood,
rejevanates
It doesn't look like rapamycin is affecting the amount of gram-negative bacteria when looking at Enterobacteria as an example (supplementary figure 6, www.ncbi.nlm.nih.gov/pmc/articles/PMC4996648/.
I haven't seen any data for LPS in blood in rapamycin-treated subjects, so I'm curious to see that experiment!
@@conqueragingordietrying1797 young blood doesn't seem to increase lifespan much,
it maybe increased nad+/ and /or decreased cd38/LPS
I'll continue cron by adf until a better treatment for ageing is found
@@conqueragingordietrying1797 I really enjoy your videos on longevity,
by cr my thoughts today;
caloric restriction is less about calories and more about time that the body has to deal with other things then food
@@conqueragingordietrying1797 I'm very interested in intermittent fasting
studies...
may prove better then cr
@@conqueragingordietrying1797 link won't let me view
Is there a supplement you can take to decrease CD38 levels?
I have a video for that, too!
ua-cam.com/video/5-2YoGctcCk/v-deo.html&feature=emb_title
Michael Lustgarten, Ph.D. Thank you sir
Apigenin?
Apigenin. Or dried parsley if you want to get it from food
Is CD38 related to insulin resistance?
I haven't looked into that, but possibly yes, because the sum of my dietary CD38 inhibitor intake is correlated with lower blood glucose levels:
ua-cam.com/video/ESCIfQp7z-U/v-deo.html
@@conqueragingordietrying1797
Good topic for your next video. If you have low levels of insulin will it help lower CD38 and increase your NAD?
Apparently cd38 and sirtuins arent even a thing according to one scientist, the name of the guy escapes my mind
Ha, likely Charles Brenner. But he's wrong about CD38 not being a big deal, see more data on this published ~2 weeks ago:
www.nature.com/articles/s42255-020-00298-z
Help me understand something. What exactly is going on with apigenin? Apparently it's a CD38 inhibitor, but this paper (www.ncbi.nlm.nih.gov/pmc/articles/PMC4156420/ ) also claims that it is an LPS inhibitor. Is the CD38 inhibition indirectly caused by LPS inhibition? Or is apigenin inhibiting both CD38 and LPS?
Another thing I'm wondering: is it actually a good idea to inhibit CD38? I understand that inhibiting CD38 raises NAD because CD38 consumes it, but since CD38 release is a response to exposure to LPS, it sounds like CD38 release *may* be useful in lowering LPS, so inhibiting it would be a bad idea and the focus should be on lowering LPS.
Obviously I have no idea what I'm talking about, please correct me! Thank you.
That paper has some great data! Apigenin isn't inhibiting LPS, but it's reducing the inflammation that is caused by LPS. To put it all into context, LPS-->increased CD38-->decreased NAD+, but also, inflammation is increased by LPS. However, apigenin inhibits CD38, thereby increasing NAD+, but also reduces LPS-induced inflammation. That's great news for apigenin!
In terms of whether or not to inhibit CD38, to minimize risk associated with that I prefer getting apignein from whole food, rather than supplementation. It's hard to believe if I eat parsley every day to get some apigenin into my diet that it will also be bad for health.
I also totally agree about reducing LPS, I'll make a video about that!
@@conqueragingordietrying1797 Thank you for your reply, that clears things up! I'd love to see a video on the connection with the gut.
Do you take NMN/NR? I've been trying to find a vendor that sells high-purity NMN, but I haven't made any order yet. Bontac (Shenzhen, China) and Oriental Yeast Co., Ltd (Japan) are often mentioned as a source in research papers. Nootropics Depot started selling it a couple weeks ago and that's where the NMN I take now comes from, but this thing is crazy expensive.
For apigenin, I agree with your approach, it's better to get it from food. I initially tried to get the pure product thinking that I would be able to get a higher dose, but the only supplier I found was Swanson, which sells 50mg pills. Dried parsley has around 130mg/g and costs way less than Swanson's pills, and you're sure that you're getting apigenin.
@@filobonda I don't take NR or NMN. My biological age is pretty good without them, and I'm confident I can continue to reduce my biological age, or at worst, slow it from increasing year-to-year:
ua-cam.com/video/85t8vmIgR6s/v-deo.html
so does gram negative bacteria seem to cause the increase in cd38,
and inflammation...
therefore causing the loss of NAD+.
I practice true Alternate day fasting,
6 days a week and truly feast one day a week.
I also drink lots of chamomile tea,
eat tons of sprouts for sulpheraphane,
drink moringa and mostly eat tons of greens avacodo and olive oil.
@@filobonda From past papers I've read, I think CD38 Knock-Out mice may have less of some cancers, but live shorter lives. CD38 is involved in many processes including development and immunity. Also there is conflicting data about levels of apigenin in parsley. The "USDA Database for the Flavonoid Content of Selected Foods" gives values ranging from 17 to 135 mg/g dried parsley.
How do we know the non-CR group wasn't just eating more 'bad' food? than the CR group. i.e. and it is actually calorie restriction that gives the reduced LPS/CR38 and not something in the food.
The study was done in mice, so they ate the same diet:
www.sciencedirect.com/science/article/pii/S1550413118305060
@@conqueragingordietrying1797 Thanks Michael. Say their food is rat poison, the non-CR group is eating more rat poison and hence will die quicker! That study is great showing microbiota composition is important - but shouldn’t eating the same food lead to the same/similar microbiota composition (just different quantities of microbiota)? Perhaps the mice innate microbiota control mechanisms have less control over the microbiota when there is more of whatever food/poison they ate (i.e. ‘standard chow’ or ‘high-fat, high-sugar diet’). Thanks
@@mwalkerdine Right, eating the same food should lead to the same microbiome composition, but the CR data clearly shows that the amount of daily calories also greatly impacts the biome and gut barrier function, among other things, too.
I’m guessing as 1mg nmn took my icnad+ from 29 to 98 my cd38 levels are minimal. I’m finding myself going back (again) to all your YT’s and harvesting more amazing insights … I’ll keep supplementing with 50 mg parsley … not for cd38 suppression but muscle integrity .. and keep 1mg nmn …ensuring optimal icnad+ (whatever that’s worth). I just ordered 6mintjs supply from donotage just in case they ban that route as well. I really think you should redo your nmn test using donotage … you may have gotten a bad batch from jinfinity.
Jinfiniti's NMN increased my NAD, so it's not likely that. My average apigenin intake is 100 mg/d, so it's not likely CD38 either, in my case. I'll have more on the NAD story soon (i.e. B6), but also something else that may increase it, without NMN, NR, or niacin.
@@conqueragingordietrying1797 it just didn’t seem to increase your icnad+ by very much. I noticed that the nmn I ordered fro. Jinfinity went clumpy in the fridge really quickly, donotage nmn stays crystalline … maybe jinfinity mixing robose with nmn was not a good idea
@@jp7357 Hmmm, my NMN from Jinfiniti is also in the fridge, and not clumpy...
I think there was a study suggesting Senescent cells produce substances that cause an increase in cd38, and some have suggested they may release such into surrounding tissue, so that might be another thing affecting cd38 iirc. Think this video by Sheekey covers it ua-cam.com/video/tvIVQr8VBD0/v-deo.html
That doesn't address the root of the problem, which includes LPS. LPS increases during aging, and induces cell senescence and CD38 expression. For ex., see
ua-cam.com/video/NGrYzOKGBXA/v-deo.html
@@conqueragingordietrying1797 True but cell senescence has other causes like shortening of telomeres, or substantial dna damage accumulation(in which case the cell can become senescent even with long telomeres ). There is also a study showing that long term CR can stop the age related decline of melatonin in primates. Melatonin is said to stimulate immune system cells, iirc. Normally without CR primates like humans show relatively drastic age related decline of melatonin. Given it's broad functions(heard it even activates telomerase and might inhibit prostate growth) it might even have an effect on the intestinal IAPs from the linked video, given it enhances alkaline phosphatases in other areas.
Dietary Caloric Restriction Prevents the Age-Related Decline in Plasma Melatonin Levels of Rhesus Monkeys -
academic.oup.com/jcem/article/86/7/3292/2848966?login=true
Drastic Age related decline in melatonin-
www.benbest.com/nutrceut/melatonin.html
www.statista.com/statistics/241572/death-rate-by-age-and-sex-in-the-us/
(of interest is that mortality in humans is lowest when melatonin production is highest in life, though that could be a coincidence)
Everybody refers to CR as a "universal" means of life extension, or as you put it "the gold standard." But has CR ever actually extended lifespan past maximal lifespan? Not to my knowledge. And if that's the case, then we need to stop calling it a "life extension" intervention, and just call it a longevity intervention. Even that may be too strong a description, given that we have yet to study CR in otherwise healthy animals. Seems like CR is only every studied in lab animals eating garbage lab chow, living entirely unnatural, and very unhealthy lives.
In other words, if you induced CR into a mouse that had the habits and lifestyle of a health-conscious human (healthy/balanced diet, good sleep, routine exercise, low stress, etc...) would it have any significant longevity effects that were *additive* to all these other healthy behaviors? We simply don't know, but one of the famous long-term CR studies done in monkeys suggests not. The study in which both the control and study groups were fed a relatively healthy diet, showed little to no effect from CR.
Maximal lifespan in mice, for example is 40 months. CR in mice has extended that to 50 months. Can CR slow aging in people? Possibly yes, based on this study:
ua-cam.com/video/vQOTkkCVAJU/v-deo.html
@@conqueragingordietrying1797 Depends on the species of mouse. Some species of mice can live up to 7 years. Others only two. For most species, the average is 3-4 (36-48 months.) You have a link for that study? Curious what species of mice were used.
The studies referenced in on that video aren't exactly what I would call definitive. We don't even have consensus on the definition of "aging." I think it's pretty hasty (and most likely entirely invalid) to refer to the improvement of a select few health metrics as "slowing aging," especially after such a short trial period.
Also, let's not be too quick to deem "slowing aging" interchangeable with "life extension." It could just be that all longevity really accomplishes is compressing the window in which we experience significant deterioration, without actually pushing back the goal post. In other words, maybe the "fast agers" have 10 years of ill-health, while the "slow agers" have only 2 or 3, but maybe they both still die around 85.