Lifespan extending compounds: from mice to mechanism - Prof Rich Miller
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- Опубликовано: 31 июл 2024
- In this video I spoke with Rich Miller, Professor of Pathology at the University of Michigan and the Director of Michigan’s Paul F. Glenn Center for Biology of Aging Research. He also contributes to the Interventions Testing Program (ITP), created in the early 2000s to study the effect of various drugs on lifespan in mice. The ITP has produced evidence for anti-aging drugs, such as rapamycin, and, in contrast, has shown a lack of effectiveness for several agents, such as metformin. We discuss the ITP findings, the biology of aging and the important questions still to address.
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Timestamps:
Intro - 00:00
Interests in aging - 01:00
Mice as a model organism - 04:00
Lessons from the ITP - 06:00
Rapamycin, mTOR & cap-independent translation - 21:00
Combining therapies - 32:30
Brain health & glucose - 35:30
Theories of aging - 44:00
DNA methylation - 49:00
Advice - 53:00
Please note that The Sheekey Science Show is distinct from Eleanor Sheekey's teaching and research roles at the University of Cambridge. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Sheekey Science Show and guests assume no liability for the application of the information discussed.
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Right to the source. This is great! Keep interviewing people who're in the middle of it all!
I like that you let the guest talk, not rushing them, then follow up and ask such informed questions. It's invaluable to hear the knowledge being shared!
The most exciting aspect of rapamycin is that it looks like its translating to humans, and many people are reporting good results.
Its very strange to see some drugs work to solve something that they are not meant to solve. Metronidazol was accidentally discovered to solve parasite issues too.
Very, very refreshing! So nice to hear from a genuine expert who is not implicitly (or explicitly) engaged in some form of special pleading! Thank you.
Thanks for posting this awesome interview! One thing that caught me by surprise was when Prof. Miller made an almost "throw away" comment at 56:11 that "...the cell senescence idea has been disproven". I have certainly heard that the theory has been refined -- from the standpoint that not all senescent cells are bad (produce harmful SASPs, etc). But as far as I know, the long-term studies championed by Dr. Kirkland at Mayo clinic are still ongoing and those outcomes are still in play.
Are you aware of any specific evidence demonstrating that the removal of harmful senescent cells is either not possible or (if it is possible) does not promote enhanced health span/lifespan?
Thanks and aha, given I work on senescence I should've challenged him, but I think he was referring to the ITP data whereby they have tested fisetin and saw no impact on lifespan. But, doesn't mean it doesn't affect other health markers.
The best interview until now..... let us hope he will get the funds to keep going forward in his interests .
@18min on moderating peak glucose is interesting. Wonder if insulin is more sensitive to peak glucose vs average as elevated insulin seems to be implicated in many health issues. Adam Antebi has shown, in mice, that low insulin raises AKG and NMN. Lewis Cantley has shown that low insulin in combination with PI3 Kinase inhibitors dramatically blunts growth/progression of many cancers. Glucose excursions also damage the endothelial glycocalyx which may be one mechanism for increased atherosclerosis. Another great discussion. Many thanks.
Very good video!I am really enjoying your presentations. You ask deep dive questions and have hands on guests. Keep it up!
Excellent discussion!! Fantastic information, and very exciting stuff. 😀
Great interview. It is frustrating for us older folks (I'm 78 and in great health but know I am aging) that the potential live extension drugs like rapamycin are not available to us. I am doing all the things that I can - walking 5-10 miles most days, keeping blood glucose low, exercising 3x week. The gate keeping by the government to limit access to drugs before some "expert panel" approves them seems irrational, and oriented to preserving a self serving funding. We have been hearing about rapamycin for years but it remains in the future. I am happy for my kids and grand kids, but wish I had access to try. Do the people working on these drugs take them? Such as Dr Sinclair and NMN? How many people would have died if we waited until the actions of Penicillin had to be known before it was used to treat infections?
Thanks!
Rapamycin is available and many people are using it already, but of course its not a proven lifespan extender in humans yet.
@@rapamycinnews How is it available? My PCP will not prescribe it for me..
@@daveoatway6126 Look for longevity doctors around the country. I think there are also ways to get rapamycin in other countries without a prescription. Either way, keep hunting and searching internet forums like reddit to find what you can.
Haha, getting the drug is not a problem. So many people are discussing whether the side effects are worth it or not (and whether there are any life extending effects in humans at all) yet some complain that it is impossible to get it prescribed..
According to dr. Alan S. Green's website (NY) he would prescribe you a recipe just for 350$. Feel free to try your luck 😁
Amazing interview! Equally amazing intellectual wisdom. Thank you for the discussion.
Great conversation!
He s my fav scientist
Cardiovascular disease is the nr 1 killer of humans. Someone told me that the r 1 killer of wild type mice is neoplasms/Cancer. Is this true? If it is true, then I wonder how this difference effects the translation of results from mice to humans?
Yes this is true. Mice mostly due to cancer in old age. Humans mostly die to CVD in old age. That’s why it’s best to lower LDL (specifically ApoB) as much as possible by following a low fat, high fiber, plant based diet with minimally processed foods consumed in moderation. Exercise too, and you can lower LDL to the point that you do not get CVD (assuming you are young enough). We know that people who have cholesterol levels as low as that of a child do not tend to get heart disease so it’s a no-brainer to lower it and avoid heart disease.
Might I suggest that saffron be looked at, as it seems to offer some sight regenerative effects......but of course does not lead to a patent so has never been studied that I'm aware.
How would politicians feel about funding a program that if successful would result in extending Social Security benefits.
If you want to live longer take Coenzyme A, it's the source of ATP. Ask the Salk Institute what they think then go to Amazon.
Interesting that Professor Miller considers senescence ”disproven," which is quite a blanket statement I hadn't heard before. Thoughts or elaboration?
Rapamycin has quite a lot of side effects, they should try to work on analogs.
Hi, isn't Rapamycin a known immune-suppressant in humans? Upregulation of cap-independent translation (CIT) might not be a good thing either as viruses use this pathway too. Susceptibility to infections might not be tested in lab mice, but in free living humans it might be a huge problem when combined with suppressed immunity.
I am not very familiar with mice research, but does anyone in the longevity research actually test any other quality of life parameters? Sure, the mice might live longer, but perform relatively poorly on cognitive tests??
What are the diets Prof Miller is referring to? Is there a good write-up of these diets available? Thank you.
What amaze me is that such a higher rank researcher is surprised by the "discovery" that controlling glucose levels would be beneficial against metabolic syndrome diseases
I believe this is the 2009 rapamycin study Prof. Miller was referring to at about 16 min in: pubmed.ncbi.nlm.nih.gov/19587680/ It's mice though. One question I would like to understand better - do mice studies meaningfully translate to humans? How do we know?
Speaking of flu shots - yearly flu shots supposedly greatly decrease the risk of Alzheimers. Maybe it up upregulates cap independent translation? He seems pretty sure the senescent cell research isn't going anywhere and yet Dr James Kirkland seems equally sure that the current clinical trials involving senescent cell elimination are going somewhere. I have a lot of respect for both Miller and Kirkland, so I'll just have to wait and see. If I am not mistaken Miller's comments were directed in Kirkland's direction. I doubt Miller has advance knowledge as they are double blind studies.
People with high contentiousness have low Alzheimers.
@@toomanymarys7355 Was that a deliberate misquote? It’s conscientiousness that’s reduces alzheimers risk.
👀 👂
"It won't be a genius level answer..."
Narrator: "It was"
Congratulations to find your long lost 😂😂😂😂😂 no to promote anything she looks beautiful
In general your videos are very informative. But unfortunately are too complicated for the common people, including myself . A good example for a well educational channel is Dr berg channel. I hope you will accept my comment in a positive spirit. Thanks
I would agree in principle, except it works for me. I find that I have to listen extra carefully and do some googling on the sidelines, but then I feel that I learn a ton and have ideas for what to read up on next.
I followed him some time until I realized that he is all about earning as much money as possible and honesty and integrity comes second place, so be careful..
Please know that Berg funds his pockets via youtube, and a background as chiropractor (neither MD nor PhD, not even an MS), whereas Dr Miller is an esteemed PhD of the highest order.
Be wary of popular youtubists - who make a living off your clicks and comments.
Yes, I realize that Berg is very charismatic and discusses popular themes, and SEEMS highly knowledgeable in many, many subjects.