Live Longer World

My guest today is Dr. Collin Ewald who is a professor at the Health Sciences department at ETH Zurich. His lab focuses on understanding the extracellular matrix (ECM) and how it changes with age. Collin explains the role of the ECM in tissue repair, muscle strength, and overall longevity. In fact, Collin’s lab is also working on establishing the ECM as a biomarker for health and disease risk. So, studying the ECM can indeed tell us a lot about the aging process and ways to intervene.

Think of the ECM as the environment that surrounds the cell or the proteins secreted from the cell. It holds our organs and tissues in place. You’ve probably heard of collagen protein - it is largely found in the ECM.

Why is the ECM relevant for longevity research? Turns out, the ECM changes with age. In fact, each cell has a unique ECM and cancer cells can be detected by their ECM composition type! There is also a connection between the ECM and the muscle, and damage to collagen with age results in weakening of our muscles.

We discuss changes in collagen with age, how sugar impacts collagen, cancer cells & ECM, the overexpression of certain collagens with age, changes in collagen causing muscle impairment with age, and longevity interventions his lab is studying to repair the impairment damage.

(This podcast can be a little technical, especially in the beginning, so I’d recommend referring to the show notes for better understanding. The video version of the podcast also contains some explanations on the video slide itself.)

All platforms / Episode Show Notes: https://livelongerworld.substack.com/p/cewald  

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DR. COLLIN EWALD LINKS: 

Lab Website: https://www.ewaldlab.com/ 

Twitter: https://twitter.com/CollinEwald   

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TIMESTAMPS:

Episode Page: https://livelongerworld.substack.com/p/cewald 

YouTube: https://youtu.be/r1Y5wGSqKWA

DR. COLLIN EWALD RESEARCH: 

The Matrisome during Aging and Longevity: https://www.karger.com/Article/FullText/504295 

Collagen overexpression increasing lifespan: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352135/ 

Youthful and age‐related matreotypes predict drugs promoting longevity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441316/ 

Doubling life near death: https://elifesciences.org/digests/71335/doubling-life-near-death

Thanks for watching & if you enjoy the episode, please like, comment, leave a review, subscribe & share!  Stay in good health - Aastha.

My guests in today's episode are Dr. Irina and Michael Conboy of the Department of Bioengineering at the University of California Berkeley. 

Their groundbreaking research focuses on tissue rejuvenation via plasma dilution and heterochronic parabiosis, where the Conboys took a young mouse and an older mouse and sutured them together, such that the animals shared blood and environment. The old mice became rejuvenated & younger. They’ve also pioneered a process called the Neutral Blood Exchange or Therapeutic Blood Exchange, through which dilution of old blood plasma can lead to true rejuvenation in the brain & other tissues of mice to a younger state!!   

Further, we touch upon Irina's work showing how decreased Oxytocin levels with age contributes to poor muscle function. Their research is incredibly exciting and we discuss all about it in today’s episode.  

Episode Show Notes: https://livelongerworld.substack.com/p/rejuvenation-via-plasma-dilution

Sign up for Premium Subscriber Extensive Show Notes & Transcripts: https://www.livelongerworld.com/premium 

Find the previous podcast episodes & subscribe to be notified: https://www.livelongerworld.com/podcast 

DR. CONBOY LINKS: Berkeley Lab: https://conboylab.berkeley.edu/  

2021 Paper Plasma Dilution Improves Cognition and attenuates neuroinflammation in old mice: https://pubmed.ncbi.nlm.nih.gov/33191466/  

2020 Paper Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288913/  

2014 Paper Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration: https://www.nature.com/articles/ncomms5082  

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Website: https://www.livelongerworld.com/

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TIMESTAMPS: 

00:00 Live Longer World Intro 

00:35 Irina & Michael Conboy Intro 

1:08 Aging is slowdown in our repair machinery 

2:55 Naked Mole Rats not extreme model for longevity 

5:37 Heterochronic Parabiosis 

16:00 Young Blood to Old Blood Exchange 

19:19 Rejuvenation via Neutral Blood Exchange (NBE) 

22:56 Old Blood Degenerates Young Mice 

25:29 Rejuvenation Effects on Brain, Liver, Muscle through NBE 

27:16 How long do effects of NBE last? 

30:15 How is NBE working mechanistically? 2 waves of rejuvenation 

33:38 Inhibiting TGF-beta & Increasing Oxytocin is rejuvenative 

38:12 NBE vs. Senolytics 

40:53 Unanswered Questions on NBE 

43:13 Oxytocin & Muscle Functioning; Notch Signaling 

48:12 Chickens & Ravens as Pets!  

Thanks for listening & if you enjoy the episode, please like, subscribe & share! Stay in good health - Aastha.

Dr. Nir Barzilai is well-known in the field of longevity and beyond and is the director and chair of several institutes focused on Aging research. Just to name a few, he is the director of the Institute for Aging Research at the Albert Einstein College of Medicine and of the National Institutes of Health’s (NIH) Nathan Shock Centers of Excellence in the Basic Biology of Aging. 

Dr. Barzilai’s research interests are in the biology and genetics of aging, so he has done extensive work studying centenarians and supercentenarians some of which he discusses in today’s episode and also in his book Age Later.  

He is currently leading an international effort to approve drugs that can target aging. Targeting Aging with METformin (TAME) is a specific study designed to prove the concept that multi-morbidities of aging can be delayed by metformin, working with the FDA to approve this approach which will serve as a template for future efforts to delay aging and its diseases in humans.  

In today's episode, we discuss centenarian longevity genes, what makes centenarians live so long and the role of growth hormones in longevity. We also dive into metformin's healthspan benefits for longevity, metformin & COVID, if metformin blunts muscle mass and causes hypoglycemia, and metformin dosage. 

Episode Show Notes + Timestamps: https://livelongerworld.substack.com/p/snbarzilai

FOLLOW NIR BARZILAI:  

Profile: https://einsteinmed.edu/faculty/484/nir-barzilai/  

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Book: https://us.macmillan.com/books/9781250230867  

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The final 2021 episode of the Live Longer World podcast is a rather special one. I've compiled some of the best & most informative parts of each of my previous episodes and highlighted them in this finale episode.   Think of it as a tour showcasing some of the work being done in the field of longevity. Some topics included in the clips are Inflammaging, SystemsAge Clock, Reprogramming, Atherosclerosis, Brain Aging and more.  And if a particular topic or clip captures your attention, you can of course go and watch the entire podcast episode.  Hope you enjoy it and wishing everyone a happy & healthy holiday season!

Episode Show Notes: https://livelongerworld.substack.com/p/2021

Find the previous podcast episodes: https://www.livelongerworld.com/podcast

2021 Live Longer World podcast episodes:

#01: Reason, founder & CEO of Repair Biotechnologies

#02: Dr. Jean Hebert on Tissue Replacement in the Brain

#03: Carolina Oliveira, the founder & CEO of OneSkin

#04: Dave Gobel, founder & CEO of Methuselah Foundation

#05: Dr. Matt Kaeberlein on Aging Interventions, Rapamycin, mTOR

#06: Dr. Morgan Levine on Epigenetic Clocks, SystemsAge Clock

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Dr. Morgan Levine is an Assistant Professor of Pathology and Epidemiology at the Yale School of Medicine. Morgan runs the lab for Aging in Living Systems at Yale. Her labs works on Epigenetic Clocks, Epigenetic reprogramming, cellular aging trajectories, and in trying to understand the causes of Alzheimer’s disease.

I can’t even begin to tell you how much I learned in today’s conversation!

We extensively discussed Morgan’s work on developing a new Epigenetic clock called the SystemsAge clock, which is very cool and can test the biological age of different organs & systems in your body.

We also spoke of different features of these clocks, interventions tested, what we know so far on reversing your biological age, some of the limitations of the clocks, why she is so excited about epigenetic reprogramming, and some of her work around Alzheimer’s disease.

Most people are interested in knowing their biological age and epigenetic clocks are a way to test it. So I’m sure you will find this conversation on epigenetic clocks fascinating and walk away understanding them much better!

I hope you enjoy my conversation with Dr. Morgan Levine.

Show notes + Timestamps: https://livelongerworld.substack.com/p/mlevine

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Morgan's Lab: https://www.morganlevinelab.com/  

Twitter: https://twitter.com/DrMorganLevine  

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Dr. Matt Kaeberlein is a Professor of Pathology, Adjunct Professor of Genome Sciences, and Adjunct Professor of Oral Health Sciences at the University of Washington. His research interests are focused on basic mechanisms of aging in order to facilitate translational interventions that promote healthspan and improve quality of life.  

Matt has been around the field of aging for a long time and knows more about the work in the aging field than perhaps anyone else. This was a comprehensive conversation where we spoke about how Matt thinks of aging from a functional perspective, caloric restriction and aging, whether NAD+ precursors are effective in slowing aging, the role of sirtuins.   

We discuss quite a bit on rapamycin and how it’s shown to be effective in improving the health of mice. Matt is very excited about the potential benefits of Rapamycin in reversing aging and he got me excited too. Matt is also working on the Dog Aging project and in trying to understand aging in dogs.   

Finally, we end the conversation by talking a bit on what good scientific practices should look like. Matt approaches his work with an unbiased lens and that’s very respectable. Matt has a brilliant mind! I had such a blast talking to Matt and I hope you enjoy the conversation as much as I did! 

Timestamps in the YouTube version of this podcast:

ttps://www.youtube.com/channel/UCcoEB1MXhkI_CFwsHRtPXUg

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Store: https://www.longevitystore.co/

FOLLOW MATT KAEBERLIN:  

Website: https://kaeberlein.org/ 

Twitter: https://twitter.com/mkaeberlein 

Dog Aging Project: https://dogagingproject.org/ 

My guest today is David Gobel who is the co-founder & CEO of the Methuselah foundation. Methuselah foundation has donated several million dollars for the advancement of longevity research and regenerative medicine. Their goal is to make make 90 the New 50 by 2030. I’m definitely rooting for that!

Dave was an entrepreneur before he decided to jump into the field of longevity. In my conversation with him, we discuss how he got excited about longevity research, companies funded by Methuselah including Oisin Biotechnologies, the concept of longevity escape velocity, his work with the super centenarian research foundation, how one can get involved in funding longevity companies and more.

I hope you enjoy the episode!

TIMESTAMPS:

0:00 Live Longer World Intro

1:30 David Gobel & Methuselah Foundation Intro

2:00 Dave's work at the TSA; Innovation at TSA

10:39 Methuselah Fund, How Dave got interested in Longevity & met Aubrey De Grey

19:14 The current healthcare system does not focus on preventative medicine; Aging is the biggest risk factor for all diseases

20:40 Methuselah Foundation mission - Making 90 the new 50 by 2030

26:56 Companies funded by Methuselah - Turnbio, Epigenetic reprogramming, Organovo 3D Tissue Printing

30: 18 Leucadia Therapeutics & working to erase Alzheimer's disease

37:20 Donating to Longevity

38:24 Investing in Longevity - how to get started

40:20 Vascular Tissue Challenge with NASA

43:05 Longevity Escape Velocity

47:28 Challenges in the Longevity Field (Money comes to winning solutions & ideas!)

51:55 Do we use money or does money use us?

57:00 Ending remarks

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FOLLOW METHUSELAH FOUNDATION:  

Website: https://www.mfoundation.org/  

Twitter: https://twitter.com/mfoundation

Carolina Reis Oliveira is the founder & CEO of OneSkin Technologies.

OneSkin is pioneering technologies aimed at extending human healthspan. Their first product is a topical supplement designed to extend your skinspan by improving skin health and skin strength. Their proprietary peptide, OS-01, has been shown to rejuvenate your skin on a molecular level and effectively treat the negative implications of aging.

Carolina holds her Ph.D. in Immunology at the Federal University of Minas Gerais in collaboration with the Rutgers University and is an alumnus of IndieBio, the world's leading biotechnology accelerator. In 2016, Carolina relocated to Silicon Valley from Latin America to co-found OneSkin, and to lead the development of the company’s disruptive rejuvenation technologies.

Carolina is full of energy and I really enjoyed talking to a scientist entrepreneur!

0:00 Live Longer World Intro 

1:06: Carolina & OneSkin Intro 

2:25 Jokes, Pleasing Indian Mom 4:00 Skin Aging; Cellular Senescence 

8:05 Skin Overlooked in Longevity Research; Concentration of Senescent Cells in Skin 

11:30 OneSkin Product; OS-1 Peptide 

17:35 Does the product work across ethnicities & skin types?  

20:55 Results from product; elimination of senescent cells 

23:42 Senomorphics (slow down progression of senescent cells) 

25:50: Results from studies in C. Elegans 

30:31 OneSkin vs. Fistein vs. Retinol 

35:21 Recommendation if using Retinol 

37:21 Senolytic Drugs vs. OneSkin 

40:19 Skin aging from Sun Damage 

42:17 Which age to start using OneSkin? 

44:47 Human Studies for OS-1 

49:08 FDA Approval for drugs 

51:00 Future products 

53:47 Excitement about Longevity Industry 

56:47 Connect with OneSkin 

58:17 Connect with Live Longer World

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Jean M. Hébert, PhD, is a Professor of Neuroscience and Genetics at the Albert Einstein College of Medicine in New York.

Dr. Hebert was fascinated from a young age by how a single cell forms the whole human body following an innate genetic program and he got excited by how knowledge of this process might be used to improve our biological fates and defeat aging.

He is a molecular geneticist by training and obtained his Ph.D. from the University of California, San Francisco, before specializing in the study of how neural stem cells form the brain at Stanford University.

His lab is now developing ways to use cell and tissue replacements to repair and rejuvenate the brain. More specifically, the Hébert Lab is engineering tissue that increasingly resembles normal neocortex, the part of our brain that performs our highest cognitive functions, and testing the ability of this tissue to integrate with the host brain.

Jean is the author of Replacing Aging.

We had an extremely interesting conversation ranging from why Dr. Hebert thinks the other methods to fight aging may not work if the goal is to beat aging, we discuss 3D organs and tissue cell replacement and we also discuss the neocortex and what it takes to replace one and lastly we talk about how plasticity in the brain works. 

Even if you are not associated with the field of longevity, you’ll find this conversation interesting and refreshing.

FOLLOW LIVE LONGER WORLD:

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Twitter: https://twitter.com/Replacing_Aging

Website: https://hebertlab.einsteinmedneuroscience.org/

Reason is the founder and CEO of Repair Biotechnologies. Repair Biotechnologies is a biotech company focused on developing therapies that treat medical conditions arising due to accumulation of excessive cholesterol. They have developed a unique Cholesterol Degrading Platform to reverse the damage that leads to heart disease and atherosclerosis. More than 5 million people die every year due to atherosclerosis and Repair Biotechnologies is trying to solve this problem.

Reason is perhaps most well known for his popular blog Fight Aging! where he distills the latest research in aging science. For anyone looking to stay informed on aging & longevity research, I highly recommend you checking it out - it’s one of the best resources out there.

In today’s conversation, we discuss how to think of aging simply, the differences between slowing and reversing aging, NAD+ boosters and their effectiveness, reversing aging using senolytics, how his company is working on a gene therapy to reverse artherosclerosis and cardiovascular disease, problems with Alzheimer's research, working towards aging rejuvenation therapies, how one can get involved in the aging space, and much more.

Note: We discuss a fair bit on cellular senescence and senolytic therapies. For those unfamiliar with the concept, cellular senescence is a process in which cells lose their ability to divide but refuse to die. When these senescent cells don’t get cleared away, they release harmful substances and damage the cells around them too.

It is well known that senescent cells accumulate with age, contributing to inflammation and aging itself. Senolytics is a class of drugs that can selectively clear away these senescent cells and they have shown promise in delaying and preventing age-related diseases.

FOLLOW LIVE LONGER WORLD:

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FOLLOW REASON AND REPAIR BIOTECHNOLOGIES:

Fight Aging! Blog: https://www.fightaging.org/

Company Website: https://www.repairbiotechnologies.com/