Extending healthspan: AKG, human clinical trials & aging biomarkers (Prof Brian Kennedy)
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- เผยแพร่เมื่อ 4 มิ.ย. 2024
- In this video I had the pleasure to speak with Prof Brian Kennedy whose lab is currently based at The Centre for Healthy Aging in the National University of Singapore. The lab uses multiple animal models combined with human studies to understand the mechanisms driving biological aging and to develop interventions designed to extend healthspan and lifespan. Prof Kennedy is also the former President and CEO of the Buck Institute for Research on Aging in Novato, California. In this video we discuss the current work that he is conducting in Singapore including the human aging clinical trials investigating biomarkers and the influence of the intervention alpha ketoglutarate (AKG). In addition we chat about what we can expect for the future for extending healthspan and discuss other aging biomarkers and challenges to achieving scalable and cost-effective health care approaches.
TIMESTAMPS
Intro - 00:00
What is aging? - 01:25
Alpha ketoglutarate extends healthspan - 06:30
Sex-specific differences - 08:30
Calcium-AKG - 09:30
Human clinical trials - 10:40
End point for trials & next steps - 14:00
Combining interventions - 17:15
Time of day & circadian rhythm & dosing - 19:30
Biomarkers for personalised medicine (or precision medicine ;) ) - 22:30
Aging biomarkers & epigenetic clock - 25:00
Scalable, cost-effective biomarkers - 28:15
What discoveries are you excited for? - 30:10
Mesenchymal stem cells - 32:30
Major hurdles for the field? - 34:20
Healthcare in 10 years time - 38:15
Advice for extending healthspan - 39:35
KEY PAPER DISCUSSED:
Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice - doi.org/10.1016/j.cmet.2020.0...
Check out @LifespanNews latest video - • Rapamycin Reduces Age-...
Icons in intro; "www.freepik.com/free-photos-v..."Background vector created by freepik - www.freepik.com - วิทยาศาสตร์และเทคโนโลยี
Hope you enjoyed the second interview!! :D
Yes i Have!!
would you please Interview Durk Pearson and Sandy Shaw?
not only for Historical Perspective, their current work must be interesting too!
😉😁
Second interview! Guess I’ll have to search your old videos.
Your question on circadian rhythm was spot on. At a minimum, researchers need something akin to a Phase Response Curve (PRC) for the agent of interest. I mean NAD+ varies by some multiple throughout the day based on circadian rhythm alone. PRC is usually used to assess the impact of the intervention on the circadian cycle, but you could do it the other way around. We could take much better guesses on mixing agents if we know their impact on circadian rhythm. If the agent is mainly thought to impact a specific organ you might need to look up the research where it is most active/dormant during the circadian cycle.
I had read Pearson and Shaws book Life Extension when it came out. I wonder why they dont seem to be a part of the online life extension community
Your so cute, from a physio & osteopath admirer. Keep up the cheeky science 🧬
Yes I did! You did a fantastic job!
I'm shocked by how few subscribers you have. I follow many science, diet, longevity and med research programs and your show is by far the best I have found on TH-cam. Your science based approach is the best.
Wow, thank you!
One reason why the host may not be getting any many subscribers as she deserves is her accent and her speed of delivery. I am a media producer, as an aside. When I listen to her speak, I must reduce the sound speed to .75 of normal to clearly understand her. Content is great! Delivery... could be better.
@@thomasjefferson8939 Pity the poor people who don't understand English English, but don't stand around waiting for them to catch up. If I can manage French and Spanish and a few others, I have no sympathy for them.
@Thomas Jefferson
Accent might be a part of it. But that I can get used to. I'm even almost beginning to be able to listen to the Indian verson of English!
Reduced speed didn't work for me, at all. I actually thought that was worse!
I don't expect her to change accent. But a better microphone usually work. Most TH-camrs seems to make that effort.
You're in my top five channels! And the other four are about cars!
For exercise, one mantra that helps for beginners is to remember that 'the first set always sucks'. Usually the first set activated the muscles enough that the second set feels much better.
Because you start out too heavy. Start out extremely light and don't go to failure gradually warm up and you will enjoy every rep and every set thereafter as you increase intensity volume and weight
Great episode and great interview. Thanks to Brian Kennedy for being on the show! One of the interesting points that Brian made is that our biomarkers probably don’t increase linearly like our chronological age, but oscillate around a mean that increases over time. I actually wonder about this when you hear an anecdotal result where something “worked” or “didn’t work”. How much of that is due to being lucky or unlucky in the moment that you performed the beginning and ending biological age test? Clinical trials with many, many participants are better, statistically speaking, but the results get watered down due to individual differences. It would be really nice if we could reduce the cost of these biological age tests so that clinical trial participants can perform them on a weekly basis and we can see how the mean changes as a result of the intervention. Anyway, great show as always! Keep it up!
Thanks Neil and exactly, timing is everything!
You are so bright and delightful. Thank you for all the great content - deep dives and you explain everything as you go.
Thank you very much this interview . please do this kind of great work 🙏
Thank you both, very pleasing video, appreciate you giving your time Professor Kennedy and recognise how you entered this field so early and got on with it. And great listening to competent interviewer.
Great interview, thank you!
Awesome interview. He's so solid in his delivery!
Impressed by quality of your questions! Just found your channel.
Thank you!
My Lord I remember how HEALTHY my Cuban Grandma was. She was 75 years old when I lived in Cuba. Never never she went to a doctor according to my Dad. She past away at 97 years old with no illnesses. My grey Grandma was 103 years old. My Dad told me how HEALTHY she was also.
aging by itself is an illness.
It's the fact of life to get older, what matters is to be healthy.
Great show. I think you're my favorite TH-camr on this so far. Great stuff!
Wonderfully interview. Thank you!
Awesome interview. Thanks!
Watching this again, such a great video.
Great interview! I am still taking my AKG every morning. Easy to take.
Great interview Eleanor! Ponce de Leon Health and Rejuvant (Rejuvant.com) are proud to have Dr. Kennedy on our team and look forward to publicizing our trials!
She does wonderful work
My new favorite TH-cam channel!
This interview is fantastic. You are great in communication. I learned many new things going around. Congrats
What an absolutely wonderful video! Thank you - much appreciated…
You are so welcome!
Eleanor!!! model material!!! been following you for years and thank you for the informative/insightful videos and explanations - always looking forward in seeing what you have for us. Keep up the great work.
Sheekey, please summarize the information from Dr. Kirkland and other experts you interview, specially about very crucial dosages. The matters are so scientific for the non-scientists like myself.
Great video's.. really appreciate hearing all you say. maybe not a question for you answer. if you wanted to take an AKG supplement. could you take an AAKG supplement or would you need to take the more expensive Calcium AKG supplement. if there a big or important difference between the two.
I would like to know about that too, even if Ornithine alpha ketoglutarate (OKG) could work
Best! I like this interview super ... "Its about sustainability and that's the key for lifestyle" thanks to Prof Brian Kennedy & Sheekey Science Show 🥰
Well tempered , even handed overview of AKG
and age bio markers 😊
Well done all around.
great site ,thank you!
Very enjoyable and informative.
Great interview and questions, well done Sheekey! Subscribed
Wow its nice to see your face at last and you are gorgeous. Excellent interview I really enjoyed it and please keep presenting updates regarding the longevity science. Thank you and I appreciate all the effort that you are doing.
Excellent interview! Very interesting subjects were touched upon throughout. Thank you both. 😁
Glad you enjoyed it!
Impressive interview & great 👍 questions !!
Curious how a combination of NAD+ , Metformin, & AKG would together result in a mice study
wOw to get Brian Kennedy congratz! Been a fan of his for years. Love seeing you channel grow. Way to go Skeekey! I appreciate that you ask different types of questions. While yes you have to ask the common ones you actually ask some in depth questions. As someone also hoping to work in the longevity and health space I see that eventually all the interview for a person are essentially the same. Great to see one that is different. Please keep up the good work I really love your channel!!!
Lance, hope your plans to work in health and longevity comes to be. Seems there isn't enough work being done. Needed are people with enough money to fund the research, development and distribution of anti aging treatments
I like the question you asked about how much calcium might have been involved in the results.
I agree with almost everything he said except for the cardiac stem cell is actually repairing damaged heart tissue from previous heart attacks and curing arrhythmias
Okay, I've been a lurker for some time now when some of your videos appeared in my feed, but I'm a subscriber now. Really like your channel!
Welcome! 😊
Thanks for an informative interview!:)
Nice vid. Do you think the NMN powder you put under your tongue works?
Very good interview.
Is the irony of frankenstein with the lightening in the background lost on everyone?
well done.
Great job!
Awesome!!
Great interview!!
Thanks!
English being my third language , I sometimes have a hard time trying to understand Sheekey . It' s not the accent, because I can understand dr. Brad Stanfield perfectly well.....
Great interview. Thanks! Do you have any videos on the Mesenchymal Stem Cells treatments? Love to know more on their potential...
Thanks! Haven't yet, but suspect i will if there is interest! 😊
@@TheSheekeyScienceShow I am very interested based on what was said in this interview. 😄
"time to deanimate..." Love it, lol. You look just like your voice... ya, that's a good thing!
😁
Both Sheekey girls are cute!
I am the only child myself too. I was born and raced in Cuba till almost 15 years of age. My grandparents lived in CUBA till they turned 103 years old . It's amazing cause my father told they were super healthy, they rarely went to doctors. I remembered my Grandma her teeth were healthy her skin was porcelain looking only use eyeglasses to read the paper. She had good hearing never sick.
can you think of anything in particular that may have helped them live a long life?
Very good interview! As always, Mr. Kennedy is very polite and political, but if you know his parlance, you can spot when he is thinking, "well, that's garbage!" ;)
I wonder about the biomarkers of aging bio markers of aging. Brian correctly mentioned that there is a metabolic network, which means it is highly connected. networks are either logistical or associative, with mixed forms possible. The important thing is that associative networks store information and can remember. This fact renders any attempt to find a small set of biomarkers of aging pointless.
Instead, we have to ask: what is normal? And normality is NOT a certain set of values each in a stupid "reference" range. Instead, normality is the capacity to react. meaning, instead looking for values, we have to check the body for its variability. The capacity to cope may be 0 even if all values seem to be youthful. On the other hand, the youthful capacity to cope (CTC) may be fully available, while some physiological markers are off the charts. Such, any "biomarker" is a 2 dimensional surface: the CTC, as a dx/dt differential, and the position in a reference range that is given by the best available ACM.
Anything else is just nonsense.
Great interview 👍🖖❤️🙏
Thank you!
Well done
Interesting. I get really noticeable results from NMN within a few hours of taking it, especially in my skin texture, but recently found I'm losing a bit of the glow. After watching this, I increased my doseage of AKG threefold and just an hour later and that glows back.
I've got so many different supplements now and it's all very experimental but I can't remember the last time I looked as good as now since I started the NMN.
where you buy AKG THANKS
NMN has been amazing with Resveratrol, and AKG and CoQ10.
@@ottoavila9895 Teriffic....try changing COQ10 for Ubiquinol, it's far better and you might think about taking Vitamin K2 (MK7) Complex which includes D3.
GlycanAge is an awesome bilogical ageing test, based on the Glycome run by Professor Gordon Lauc in Zagreb Croatia.
I'm confident that putting together these excellent videos helps you to think throught the issues and understand them better yourself - so it's a brilliant way to keep your education current. Could you also do one on your own work? i.e., what specifically is your phd goal and what experiments are you personally working on?
It does! Have made one on my labs focus area, "why we study senescence". Will think about doing one for my project. But will of course make a video if my work gets published
Besides being transformed from Isocitrate, where else is Alpha-Ketoglutarate synthetised?
Love it 🔥
Article by Gerendai et al 2002, 'Supraspinal connections of the ovary...' about neural pathways directly connecting the ovaries to key brain regions including hypothalamus and locus coeruleus. Unfortunately it is paywalled so I can't access it... Differences in neuropeptide signaling could be related to sex differences in responses to geroprotectors? I hope the studies Dr Kennedy has planned on 45-65 yrs are large enough to detect differences between pre- and post- menopausal women.
Re: sleep - dependent on locus coeruleus; way to influence LC function is thru breath training, also I suspect anthocyanin consumption can help. Best breath training method I've found is 4-7-8, see Andrew Weil videos on how to implement.
I love it! Keep them coming! You're doing great with this channel! You should add your patreon info in the description of your videos for more exposure.
Thank you!! 😊
Great interview! Are you aware of any of the substances/molecules that he referred to which "cancel each other out"? Conversely, are there any which work particularly well synergistically?
Thanks! ITP showed metformin & rapamycin to be better combined for lifespan increase than either alone in mice phenome.jax.org/projects/ITP1
Switch from Coke to Diet Coke? Better switch to water! And coffee and tea (without sugar ofcourse). Great interview!!!
Thanks. Good discussion. In the US at least, properly regulating the food industry, especially fast/processed foods, would make a major positive step change across society. As it is, our food is a major cause of early morbidity which then leads to 10s of millions of people being shuttled into an overpriced low quality medical system.
The US is a lost cause
Does anyone know what study is shown at 14.19 ?
Hi Eleanor, is there an audio version anywhere (like on iTunes or Spotify etc)? If not would be great to upload the interviews there as well for people (like myself) who prefer audio for longer form stuff. Might also help with exposure.
Not yet, but will consider!
Curious I am taking L-Arginine AKG supplement is the calcium version of AKG better
Great science to be looking at vit A for example, iaimed to find help for an aging population, rather than quick market profit.
Excellent interview!
How do we know it doesn't just reduce the the production of markers
Sassy video again! Top marks!
Is time release Calcium AkG better than the POWDER form.? I would like to know before I buy the POWDER I saw it advirtize here in California, USA.
Nor Calcium nor time release sound good to me. Also, you might wanna search "do you need alpha-ketoglutarate?" on youtube.
19:00 I would prefer it if supplement makers made smaller pills and have the dose be 2 pills or more, and perhaps scaled to body weight.
okay, he addressed personalized dosing later on ... also mentions vit E; vit E studies need to be be re-evaluated given the interaction with COMT genotype (in women, don't know if it applies to men). Also, still no clear rationale given for why vit D vs vit A in men's & women's Rejuvant products. re: vit A - humans have potential to have accumulated lead in bones over lifespan and vit A can increase bone resorption & mobilize lead.
Also, why are all the pills white?
Shouldn't they come in a full array of colors for every different personality type?
Where can we buy 17alpha estradiol supplement
what is the difference between AKG, AAKG and CAAKG? which is most helpful for longevity?
Wouldn't the ca in the ca akg calcify the arteries?
@@noname-nu6oo no
What was the outcome of the Rejuvant trial? Brian is interesting, but only ever seems to talk about what he is investigating rather than discussing results which is what we all are seeking. Maybe you can do an update interview with him?
LOVE TO LEARN FROM YOU
Why do levels of AKG go down with aging?
What I can't believe is how fast mct oil gets into the brain. You see, when I have carbs the day before my brain produces visual artifacts that look like migraine type visual patterns. When I go to the fridge to take morning mct oil. Before I have even left the fridge the artifacts have already disappeared in my vision from getting energy to the neurons lacking energy because of insulin resistance.
Is there any information on the efficacy of liposomal Alpha-Ketoglutarate vs non liposomal formations? Also what about Calcium Alpha-Ketoglutarate vs regular Alpha-Ketoglutarate? I would slao be curious about it's affects on metabolic syndrome, type 2 diabetes, blood sugar hba1c markers etc.
I'm doing the research on a male 89 years of age have not yet had his DNA read my 23 and me or others to determine his actual DNA age identified by any biomarkers and am curious as to the differences between the two of the couplings you mentioned. I'm starting him on the 1 gram alpha keto glutamate along with victims A starting today. I'm hoping to see positive results as the participants did in the Israeli trials have shown through their ongoing trials. As soon as I learn the differences I'll reply again. Nice to meet you
Does taking Nicotinamide Riboside with Ca α‐KG cancel each other out?
A question, would L-ornithine alpha-ketoglutarate (OAKG) have the same effect as alpha-ketoglutarate on its own, assuming one took 3 grams of (OAKG) but the body could only get 1 gram of ( AKG ) from the 3 grams of (OAKG) would it give the same results as taking just 1 gram of ( AKG ) does anyone have any thoughts on this, thank you
Why would the body only get one G since it was 3 G that you took it would still get the entire 3 G it would just get the benefit of the amino acids salt as well
@@reggiepalmer6157 Sorry I didn't explain, most sales companies of OAKG are formulated 2 parts L-Ornithine to 1 part AKG, and it also applies to AAKG sales as well, so one ends up taking lots more of the things you weren't particularly looking to take, thanks
pharma companies bidding billions for startups drug discoveries because they have models that show they can charge tens of thousands of dollars per treatment guarantees affordability is the least of concerns.
Would you be willing to do a video on Nootropics because I have ADHD and my short term memory is the worst so I was trying to look into it but I don't really know what to trust in terms of what actually works and thought it might be right up your alley
Spermidine keeps the brain young, prevents Alzheimer's...look into it.
Great interview. However I'm starting to think that these methods that use some random already existing drug just don't seem like they are very likely to work out. I mean what's the chance with the human body and all of its complexity is going to be manipulated into living longer with a simple compound? I think Dr Kennedy is great and I love in his enthusiasm and ability to explain the importance of fighting aging what he said there about looking into cellular reprogramming and techniques like this seem like the fastest way to big progress.
What they can do now with using things like RNA seek and looking for all these different levels of how the genes are expressing at any point in time and then looking for the signaling networks that go on between cells and within the cell. Well I don't know if I'm making this up but I think that this is possible now. It seems to me that the way to solve these problems is to use a computer that would analyze almost every potential interaction. I'm not sure if this is possible maybe there are just way too many combinations. But the ability to turn on and off genes en masse and then look to see how the signaling networks are affected. They Could you use these techniques to see what happens during embryonic development? To see how the cells are reset back to zero. Perhaps there is a way to do that cleanly perhaps there is a way to use those mechanisms that exist in all of our cells whilst keeping the cells functioning normally.
Anyway, I'd love to see an interview between you and dr. Ana Cuervo and another with Dr. George Church.
Also on the flip side is Dr. Manolis Kellis. He actually does this sort of computational exploration of signaling networks using perturbations and huge numbers of gene expression readings... And he seemed to think that the human body is just built this way & if you want to live significantly longer, it would need to be redesigned from the ground up.
Wow this comment turned out to be an entire new episode!
haha, thanks! RNA-seq does help address these questions but it is fundamentally the protein level in which "function" occurs so i think it would be more complex!
@@TheSheekeyScienceShow If RNA-seq reads an RNA it means that both the genes & the epigenome are doing their job, correct? What else could go wrong down the chain from there? Well I suppose plenty, but not across the entire organism, or there would be some very big problems.
As a programmer I understand this approach to debugging a black box (the inifinite complexity of a hundred thousand proteins interacting.).. you just start flicking switches in different combinations to see what happens on the other side.
This is what Manolis Kellis seems to do. He comes from a computer background, but is totally into biology... he's worth a watch if you haven't seen him before, I'd say. He was also recently on Lex Fridman's podcast where he talked about the wonders of all this stuff & the breakthrough massively parallel techniques that now let them zero in on a few genes that seem to be the culprits for certain systemic outcomes like obesity, for example.
If George Church comes on I'd like him to be asked if he wants to live forever in this physical universe and if it is possible to get longevity escape velocity in our lifetimes. It seems last time I heard him talk about this he danced around it.
I take CaAKG but I worry the calcium will clog my arteries. Many warnings if you take calcium every day you are at risk for early clogged arteries. Any thoughts on this?
Take it with Vitamin D3 and K2, which are supposed to stop that.
Wow....nice to finally see you! your a beautiful young lady from an old lady)! thank you for your interview. I take AKG, MNM, and 35 other supplements and feel better than i did at 35 (i'm 58). Hugs and thank you young lady!
Curious … what others? & what brand akg? I’m 49… tick tock! :)
Good Day ...
Thanks in advance ...
Please, can you tell us the types of supplements that you are using
@@mshkt1620 Just watched Bradley Stanfield and he recommended 1500 mg NAC morning and night for glutathione production in peeps 50 and over. I started and feel good on it and sleep is good. Video on You tube check it out.
Great choice of questions. Like these interviews as the pace is a bit slower for me :)
Hi have you talked with Dr David Sinclair?
I am hoping to at some point but he is a very busy man!!
Woah now, what supplements seem to be cancelling each other out? You should have followed up on that!
soooo, how do you reverse aging?
So what does akg do for you outside of less gray hair
AKG is not proven to reduce gray hair in humans.
Unfortunately AKG is very expensive via Rejuvant. Not sure how efficacious other products are.
Where can i go to check my biological age?
no mention of toxic pufa?
👌
he said sustained release is best for humans...what about liposomal? Is sustained release better than liposomal?
why your Skin look so perfect
On the other side of 75 I will try akg to see if there is a reduction of voice hoarseness. This has only occurred after 75 + 6 months. Be interesting to see. Taurine should have done this but the major effect of taurine was a reduction in night vision. I walk my dog before daylight and my view through a forested walk area is noticably decreased with taurine. I am taking 1000mg and at a 2xs increase a further reduction in night vision occures. Before taurine my view of the walk area was clear to the end of the walk area 1/2 mile. Now clearly inhibited.
What about aakg?