SIRT6 Positively Affects The Hallmarks Of Aging And Extends Lifespan
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- Опубліковано 4 лип 2024
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Papers referenced in the video:
Sirtuins, Healthspan, and Longevity in Mammals
www.sciencedirect.com/science...
Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH
pubmed.ncbi.nlm.nih.gov/24011...
Resveratrol improves health and survival of mice on a high-calorie diet
pubmed.ncbi.nlm.nih.gov/17086...
Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice
pubmed.ncbi.nlm.nih.gov/20974...
Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer
www.nature.com/articles/ncomm...
Restoration of energy homeostasis by SIRT6 extends healthy lifespan
pubmed.ncbi.nlm.nih.gov/34050...
The sirtuin SIRT6 regulates lifespan in male mice
pubmed.ncbi.nlm.nih.gov/22367...
SIRT6 in Senescence and Aging-Related Cardiovascular Diseases
pubmed.ncbi.nlm.nih.gov/33855...
Calorie restriction-induced SIRT6 activation delays aging by suppressing
NF-κB signaling
pubmed.ncbi.nlm.nih.gov/26940...
Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6
pubmed.ncbi.nlm.nih.gov/27101...
A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer’s Disease, Aging, Cancer, Inflammation, and Diabetes
pubmed.ncbi.nlm.nih.gov/33920...
Acute Exercise Leads to Regulation of Telomere Associated Genes and MicroR A Expression in Immune Cells
pubmed.ncbi.nlm.nih.gov/24752...
The effect of 12-week resistance exercise training on serum levels of cellular aging process parameters in elderly men
pubmed.ncbi.nlm.nih.gov/32919... - Наука та технологія
I love the way you break it all down! Thank you!
Wow... You do sounded very excited about this. Thanks for the video.
Good stuff! Many thanks for your hard efforts.
Thanks Lucky Hanger 13!
Mike, another great and informative video! Thank you 😁👍
You made this so easy to understand for the layman. Thank you for this great analysis!
Thanks Helen, I try to do that, so it's good that it comes across as relatively easy to understand!
excellent video - thank you - much appreciated!
Michael good video, yes when you have a chance please make a video about supplementation.
Thank you! Amazing content!
Great Content
informative. SIRT6 and mTOR are the most important ones, a nature paper says Cyanidin is the most potent SIRT6 activator we know so far
Cyanidin? Where would you recommend obtaining this naturally in the diet for maximum benefits?
@@littlevoice_11 berries
"[Cyanidin]It is a pigment found in many red berries including grapes, bilberry, blackberry, blueberry, cherry, cranberry, elderberry, hawthorn, loganberry, açai berry and raspberry"-wiki.
Black elderberry was shown in a previous video of this channel to have the most potent inhibitor of CD38 also, iirc.
@@diamond_s thank you. I was unsure which was the best of the (berry)bunch
@@littlevoice_11 Cyandin is most abundant in black elderberries-see the list here:
www.ars.usda.gov/arsuserfiles/80400525/data/flav/flav_r03-1.pdf
excellent, clear presentation!
Thanks rfbead321!
Very informative, thanks.
Excellent!
Your work has been very good 👍 👌
Thanks Great Awakening!
Great summary of SIRT research! I'm looking forward to Part II, assuming you're going to make it.
Thanks Gokhan. What would you like to see in a Part II?
@@conqueragingordietrying1797 Icariin is super interesting as it was shown to extend mice lifespan earlier. Fucoidan is all the talk (with exclusive availability from one supplement provider?), though I'm not sure how strong is the backing data. I also wonder if blueberries and other berries slow down or stop DNA damage, perhaps through other mechanisms than SIRT6? Or is it cyanidin? I feel slowing down DNA image is very important. Summarizing the current research on interventions would be very helpful!
@@MrStarchild3001 Definitely, thanks Gokhan, I'll put it on the list. Other videos are currently ahead in the queue, so I can't guarantee when.
Absolutely fantastic Mr. Lustgarden. You are a powerhouse when it comes to this stuff. So, do we expect that perhaps fasting activates Sirtuin 6 at all? I guess in the meantime Sirtuin 6 activators and excercise could be used.
Excellent! Fucoidan, from brown seaweed seems to be the best SIRT6 activator
Excellent presentation Michael. SIRT 6 plays an important longetivity role in both genome maintenance and tumour suppression
Thank you
Thanks Jim Dres!
Suppress tumors by taking lactoferrin or artemisinin.
I just subscribed to your channel because of your presentation and the links to referenced articles. Can you recommend scientific articles on pain reduction in chronic Lyme and other tick-borne diseases in humans?
Great info, keep it coming! To clarify, resveratrol does increase SIRT1, but does NOT extend lifespan in healthy mice?
Based on the Baur 2006 paper in the video, resveratrol activates SIRT1, but there's been a lot of data and debate since then (2006) about whether it actually activates SIRT1 or not.
Thanks Michael. I saw a recent talk be Vera Gorbanova, who's lab works on aging, where she also pointed out the importance of DNA repair as facilitated by SIRT6. Other studies have shown that older people who have a high polyphenol content in their diet live longer with lower morbidity, which now seems to have at least a partial explanation given the list of activators which you showed. Full circle back to scientifically based diet and exercise.
And blood testing! Otherwise it's just a reasonable guess, and I prefer greater specificity.
@@conqueragingordietrying1797 is there a video in which you discuss how to use the results of blood testing? I don’t see how you can control for one dietary/lifestyle intervention at a time, without taking many years to see how labs change between interventions. Even if you have the patience to do this, other lifestyle factors may change beyond your control in between blood tests.
@@Avital4414 Unless you're a mouse, which can have the diet completely controlled, the 1-at-a-time approach is very difficult, and will take a long time to sort out. For example, to see if it's a real effect, you'd need a few measurements before, then a few during, and a few without it. That process alone is a few months (at a minimum), if not longer, for testing. In contrast, I make multiple interventions for a given dietary period with the hypothesis that the real effects will more strongly correlate with a given biomarker (s) over time, and if they're not real, they'll weaken over time. So far so good, as I've made consistent progress in slowing age-related trends for many biomarkers, including albumin and creatinine. But also not that this approach is also time consuming, and to try to minimize that I test ~6x/yr. I could test even more often, 1x/month, but I haven't progressed to that, yet.
At some point I'll make a video specifically focused on the approach-I've touched on it in many videos, but not as comprehensively as I can.
Excellent video. Could you educate us the right dosage to take the amounts of supplements required to activate Sirtuin 1 & 6.
That's tricky-as far as I know, there are no RCTs for SIRT6 activation improving health-related outcomes in people, so that dose, for example, is unknown.
Is Sinclair correct about olive oil being a better SIRT6 activator than Resveretrol?
I haven't looked into that data, that's likely a topic for another video in terms of the best SIRT6 activators. I didn't see resveratrol on the list for SIRT6 activators.
Thanks for sharing. Are there any molecules that inhibit SIRT6?
SIRT6 activity is a balance between inhibitors/activators, so in a future video, I'll explore that.
Doctor Mike I live in San Diego where can I get MNM RESVERATROL AND SIRT 1 AND 6 THANK YOU
PGC1alpha ?? I'm now a bit confused - thought it was, in general, better to stimulate increases in PGC1a (to a point). But at 3:30min PGC1a acetylation (increased expression, correct?) was decreased in HF diet when SIRT1 was increased. So, does this mean that increased SIRT1 decreases PGC1a? Or is this only applicable to HF diet? Or should we stop SIRT1 overexpression to avoid impacting PGC1a negatively? Any thoughts?
Hi Michael , does Luteolinidin have a direct positive effect on SIRT6 besides increasing NAD levels ? Thanks David
Hey David, I've yet to see any data that luteolinidin impacts SIRT6. Luteolin activates it, though.
Really looking forward to the sirt activator diet.
likely will include methionine restriction
@@robertnewton5343 basicly diet high in plants and low in animal based foods then if thats the case, cuz animal products have way higher levers of methionine then plants
@@Pawland000 somehow bacon and cured meats have massive levels of methionine :`(
64x
I'm surprised about the negative SIRT1 results. I wonder if there is an obvious reason? And how much more activation of SIRT6 is required? Is there a Goldilock's region?
With Resveratrol and the SIRT 1 studies do we know if they are giving Resveratrol with fat as this significantly affects the bioavailability of the results hence why it may been seen to have little effect?
The only effect of resveratrol on lifespan was when the mice were on a high-fat, obesogenic diet. That data is in the video. As far as I know, there's no lifespan data for resveratrol supplementation when mice are on a high-fat, eucaloric diet.
Does Resveratrol affect both SirT6 and SirT1 or only SirT1?
Do we know how long SIRT6 remains elevated after exercise? Do we know how long it needs to be elevated to have a significant lifespan effect?
There are few studies looking at SIRTs levels after exercise, but the 12-week strength training paper referenced in the video suggests that SIRT levels remain relatively elevated as long as subjects exercise, when compared with non-exercised subjects.
Would ptersilobene be more beneficial than reservatrol sine it has more bioavailability??
I haven't looked into pterostillbene's effect on lifespan, but if that data exists, please post it here!
Hi Doc. Love all your videos. I understand resveratrol activates sirtuin 1 genes. What activates Sirtuin 6?
That info is in the video...
So doc. How to get ergothionine? Supplements & take mushrooms? Put medical journals aside, what do you do to increase Sirtuin 6 activation?
@@zulkiflicurran94 Mushrooms would be the best way to get ergothioneine (see ua-cam.com/video/UEgBxCk9fb0/v-deo.html)
To increase SIRT6 activation, I'm on mild CR (~10% reduction), exercise regularly, and include foods that contain SIRT6 activators (i.e. blackberries for cyanidin) every day.
@@conqueragingordietrying1797 already watch your ergothionine videos. I like it a lot. Make more videos doc on aging. I am a big fan
@WILL HOLYGONS Calorie Restriction
❤
If exercise increases sirt6, I wonder how supplements that decrease the impact of exercise, such as nac, affect sirt6, and what can be taken to increase sirt6 expression on its own...
That's a major reason why supplements are last on my anti-aging list. And if they are included, blood testing to see if they work, or not (or are detrimental!).
Does NAC really decrease the inpact of exercise?
I found this in an abstract on PubMedd:
"Participants supplemented with NAC showed significant improvements in exercise performance, antioxidant capacity, and glutathione homeostasis. However, there was no clear evidence of beneficial effects of NAC supplementation on haematological markers, inflammatory response, and muscle behaviour. NAC supplementation appears to be safe and may regulate glutathione homeostasis, have antioxidant effects, and improve exercise performance."
Another talked about benefits for exercise for those with low Glutathion. And no effect for those with better values of it.
This was just me doing a short look for any confirmation of your statement.
So, not anything authoritative.
what is meant by overexpression, and is overexpression necessary for a positive result?
Mice were engineered to have higher than normal levels of SIRT6, i.e. SIRT6 was overexpressed in transgenic mice, when compared with the level in regular mice.
In this study, SIRT6 overexpression extended lifespan, so yes, it was necessary for the positive result.
So SIRT6 is influenced by calorie restriction. One question I have is what is calorie restriction per person? How many calories equal a restriction? 30% less than what? Also, would SIRT6 be activated by these fasting mimicking drugs like Rapamycin?
Prolonged Fasting, ZERO calories.
Are there enough studies out there to do a video on INKT cells and their senolytic potential. I saw that oyster mushrooms may increase INKT cells. I am not sure if there are other less expensive substances that might do the same job. Anyway, that's a video suggestion for your consideration.
Thanks jack buaer. If you post the paper links, I can take a look. If UA-cam blocks the links, post the paper titles, I'll look them up.
@@conqueragingordietrying1797
This is all I know of. I don't know if there is more out there.
www.ucsf.edu/news/2021/05/420506/scientists-find-mechanism-eliminates-senescent-cells
www.sciencedirect.com/science/article/pii/S266663402100163X
www.researchgate.net/publication/305642672_A_Potent_Pharmacological_Mushroom_Pleurotus_eryngii
Good stuff, thanks@@jackbuaer3828. This is definitely on the video to-do list, but later rather than sooner. To do it justice, I'll need to read up on it, I haven't looked into clearing senescent cells as an anti-aging strategy.
good ole Quercitan
Maybe the overexpression of sirtuins in mice doesn't show better results because the NAD levels are not overexpressed, so the sirtuins can't fully act without enough NAD... I think it doesn't matter if you have a lot of sirtuins if they aren't being activated with NAD, right? Or am I missing something?
When you say "overexpression of sirtuins" in mice, you must be referring to resveratrol, because the SIRT1 TG studies show no effect on lifespan (data in the video). Interestingly, SIRT6 TG mice have higher levels of NAD+ than WT (it's in the Roichman 2021 paper), so it's a win-win for that and lifespan.
@@conqueragingordietrying1797 thank you
Isoquercetin activates sirt6, large doses of other quercetins activate sirt6 however small doses of other quercetins inhibit sirt6-it is important to get the dosage or type of quercetin right.
Yes, good point!
how high a dose of quercetin would activate it?
@@robertnewton5343 no idea... I wish I could work that out, I guess i'll just be experimenting with the maximum recommended dosage, it's also worth knowing that bromelain helps to metabolize the quercetin thus making it more potent.
@@pelletey DO you think fasting activates SIRt 6? I know it activates Sirt 1 and 3 strongly. I guess even if fasting does not activate it, that it is good that caloric restriction seems to activate Sirt6
@@robertnewton5343 not sure, if cr does than it probably does. Fasting increases NAD+ too so that will help with sirt6 throughput I guess
Have any adverse effects ever been associated with increasing SIRT6 levels?
I didn't come across that in mice, but if that data exists, please post it...
@@conqueragingordietrying1797 Excellent research Michael. I did come across some data that suggests SIRT 6 has the potential to act as a cancer suppressor AND cancer promoter depending on the type of cancer. Very interesting read especially section 3. www.mdpi.com/2072-6694/13/5/1156/htm Seems similar to what I've read about taking NMN where it may raise NAD+ levels to possibly reduce the risk of getting cancer , but can act as a cancer promoter also. I remember seeing Dr. Sinclair elude to this where he said if he was DX'd w/ CA , he would stop NMN.
say that if he was DX'd w/ CA , he would stop NMN.
sirt6 increase max lifespan but exercise dont..... means exercise is actually a negative factor ?
I'm interested in that Methionine restriction seems to mimic calorie restriction.
And that Glycine seems to blunt the effect of too much Methionine.
It seems like there isn't as much excessive protein, as too little Glycine, which affects lifespan.
How much of the above is correct, false?
I haven't yet found a good exposition of these things.
That's pretty odd, because it isn't that new information.
Perhaps researchers like CR too much!
I read people take TMG with Niacinamide
11:00 😳80% of max for 30 mins 😢
Since i have been eating lots of berries, mushrooms, kelp noodles, high oleic acid foods, and lifting and running for several years, hopefully, it has been doing something beneficial. These habits were known to have a high amount of health benefits before their association with Sirt 6 through social media. If you have been following generally accepted health based diet and lifestyle advice, it appears that you were activating Sirt 6 all along (probably without knowing it).
what kind of mushrooms?
@@robertnewton5343 - Magic mushrooms ? ;-)
@@robertnewton5343 Plain grocery store organic white button mushrooms have lots of health benefits and are a source of ergothioneine
@@jackbuaer3828 oh fantastic. Man I love mushrooms with some red wine vinegar too. Great news
@@robertnewton5343 Agricultural Research Service (ARS)-funded scientists have conducted an animal-model and cell-culture study showing that white button mushrooms enhanced the activity of critical cells in the body's immune system.
www.ars.usda.gov/news-events/news/research-news/2010/researchers-study-benefits-of-white-button-mushrooms/
We previously showed that dietary white button mushrooms (WBMs) enhanced natural killer cell activity and that in vitro WBM supplementation promotes maturation and function of dendritic cells (DCs)
pubmed.ncbi.nlm.nih.gov/24259557/
A 1/4 cup of mushrooms (any kind) daily was associated with 45% lower risk of cancer
www.sciencedaily.com/releases/2021/04/210421200133.htm
A 2021 n=3,236 study "Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease" found:
"Increased level of the amino acid ergothioneine was strongly and independently associated with both a health conscious food pattern and a lower risk of future coronary artery disease and cardiovascular and all-cause mortality."
Haha, new subscriber. Just saw your ergothioneine video from last month:
ua-cam.com/video/UEgBxCk9fb0/v-deo.html
Not so clear. Research material shows that quercetin can inhibit sirt6 as well as to serve as sirt6 activator. It is dose dependent. It is not clear how much quercetin should be taken and whether regular quercetin consumption which helps lower inflammation and therefore ensures raised levels of nad+ on one hand would in parallel serve as sirt6 inhibitor on the other hand, be ok to regularly take. So are benefits partial or is it possibly problematic when consumption is consistently low level on regular basis. Maybe high doses quercetin should be taken for short period of time and then to fall back to taking low dosage. Some other research shows quercetin has kidney protective effect, however at high dosage can cause kidney damage. Possibly short intervals with boosted levels and fall back to lower level consumption could fit. Similar to senolytics approach. (Where quercetin is also known to take an active part anyway)
quercetin is fascinating, i have a ton of it here which i dont want to go to waste. Seeing as higher dosages are more appropriate we should be taking it with bromelain to activate it, also isoquercetin seems more reliable for a stronger dosage.
I think the easiest answer is to get SIRT6 activators from food, to minimize any dose-dependent effects. Alternatively, blood testing to see if SIRT6 activators/inhibitors like quercetin are net beneficial, neutral, or detrimental should be on the list, imo.
@@conqueragingordietrying1797 does supplementing via food help because it's easier for the body to regulate the metabolism rather than if a pure supplement is taken?
@@pelletey It's harder to overdose on a nutrient via food, which would make it the lowest risk approach. Not maximal gain, though. Alternatively, supplements would have the greatest potential gain, but also the higher risk.
How much did resistance training increase SIRT6 vs running 30 min?
It wasn't as much as the effect of running, but still elevated when compared with non-exercised subjects.
New studies proved Resveratrol , fisetin and quercetin has no effect on life span
Who's the guy who's always grinn8ing ear to ear, Brad something or other, who says resveratrol harms you?
Dr Brad Stanfield said the same thing
About SIRT6?
Your presentation is great, but just to make sure that I've understood this correctly, as I'm not a science type, the initial research showed no improvement in female mice and the later research was carried out on males only. So for 51% of the population there's actually no evidence to suggest that this supplement works? Have I understood that correctly? I've been considering buying the sirt 6 Activator but I'm trying to find data on females, even if it's just mice. I understand why studies have been carried out on males historically, but it can be tricky trying to find out what is meant when people say studies apply to people, when what they actually mean is male mice or men. I always appreciate it when these distinctions are made because longevity supplements aren't cheap so I only buy where the evidence relates to women specifically.
Michael, it would be great if you put some mice on your best diet and exercise interventions to determine the impact on their lifespans. I realize that they may respond somewhat differently than humans, but it would be very encouraging if the lived 30-50% longer and healthier.
Yes Ed, definitely. I have a grant starting sometime this year that will test the effect of a high soluble fiber diet on muscle mass, muscle composition, and physical function in aged mice. If that goes well, then I'll propose a lifespan study...
Fisetin
Yep, fisetin is a known SIRT6 activator, but I'd be wary of supplementing with the goal of optimizing SIRT6 because many metabolites can be also SIRT6 inhibitors at high doses. Or, even better, that can be assessed with regular blood testing.
You still gettin huge scary linear death wall even with SIRT6 boost, we need more harcore science, aging is stupid, naked mole rats mortality graph for humans! :D
I'm pro-rejuvenation tech, but maximizing my lifespan with every trick in the book can help me (and others) get to longevity escape velocity, whenever that happens.
@@conqueragingordietrying1797 It is all about Hype, just like bitcoin, scientists need to show middle age rat or dog and double its lifespan with all of the zombie cells cleaning, retrobiom inhibitors, SIRT6 boosters, rapamycin.
Just rejuvenate some dog on TV and industry will get it first trillion in a single year 100%
@@pavelbaidurov228 Lifespan is regularly extended in mice, it's only a matter of time before that's consistently true in people. The question is when-in the next 50y or 500?
@@conqueragingordietrying1797 I think "money first" We need some Hollywood things in order to get money(probably from governments under elections pressure) for much more experiments in parallel. This field is sooo poor, People collect donations on reddit
@@pavelbaidurov228 Unfortunately, that's wishful thinking about getting more $ for this. That's why I try to take control of my own health, because, as you mentioned, there is so little invested into aging research.
Speaking way toooo fast! Had to continually stop the video and study the graphs! Frustrating...
Hey Richard Ayala, that's my style. In contrast, most videos are too slow for me, and it's ok to stop the video to study the graphs!
Annoying to have to fast forward 5mins just to get onto SIRT6. Better a very brief intro that references past videos than the same content over and over.
Also why do you call it "Sir.. T6"? The Sirtuins are SIRT then the number. So SIRT-6. Go to any interview, all the scientists reference it that way.
A better title would've helped that-what would you recommend instead?
@@conqueragingordietrying1797 I think the title is good, as is the content and coverage from 5mins 👍👍
Thanks @@Libertas_P77. I wanted to put SIRT1 in the title, but it would be too long. I'm always open to changing things for the better, though!
Pde4 inhibitor increase Ampk-Sirt6 - www.ncbi.nlm.nih.gov/pmc/articles/PMC6188481/