The Life-Extension Episode — Dr. Matt Kaeberlein on The Dog Aging Project, Rapamycin, Metformin, Spermidine, NAD+ Precursors, Urolithin A, Acarbose, and Much More (#610)

“I constantly tell the people in my lab and other scientists, ‘You’ve got to do the experiment.’ You cannot go into it thinking that you know the answer and not do the experiment because your dogmatic belief says, ‘This is how it’s going to work.’ You’ve got to do the experiment.”

— Dr. Matt Kaeberlein

Dr. Matt Kaeberlein (@mkaeberlein) is a professor of Laboratory Medicine and Pathology at the University of Washington School of Medicine, with adjunct appointments in Genome Sciences and Oral Health Sciences. Dr. Kaeberlein’s research interests are focused on understanding biological mechanisms of aging in order to facilitate translational interventions that promote healthspan and improve quality of life for people and companion animals.

Dr. Kaeberlein is the founding director of the University of Washington Healthy Aging and Longevity Research Institute, the director of the NIH Nathan Shock Center of Excellence in the Basic Biology of Aging at the University of Washington, director of the Biological Mechanisms of Healthy Aging Training Program, and founder and co-director of the Dog Aging Project.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, Google Podcasts, Stitcher, Amazon Music, or on your favorite podcast platform.

Brought to you by Levels real-time feedback on how diet impacts your health, Athletic Greens all-in-one nutritional supplement, and LMNT electrolyte supplement. More on all three below.

Listen onApple Podcasts

Listen onSpotify

Listen onOvercast

This episode is brought to you by LMNT! What is LMNT? It’s a delicious, sugar-free electrolyte drink mix. I’ve stocked up on boxes and boxes of this and usually use it 1–2 times per day. LMNT is formulated to help anyone with their electrolyte needs and perfectly suited to folks following a keto, low-carb, or Paleo diet. If you are on a low-carb diet or fasting, electrolytes play a key role in relieving hunger, cramps, headaches, tiredness, and dizziness.

LMNT came up with a very special offer for you, my dear listeners. For a limited time, you can get a free LMNT Sample Pack with any purchase. This special offer is available here: DrinkLMNT.com/Tim.

This episode is brought to you by Athletic Greens. I get asked all the time, “If you could use only one supplement, what would it be?” My answer is usually AG1 by Athletic Greens, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. I do my best with nutrient-dense meals, of course, but AG further covers my bases with vitamins, minerals, and whole-food-sourced micronutrients that support gut health and the immune system. 

Right now, Athletic Greens is offering you their Vitamin D Liquid Formula free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit AthleticGreens.com/Tim to claim this special offer today and receive the free Vitamin D Liquid Formula (and five free travel packs) with your first subscription purchase! That’s up to a one-year supply of Vitamin D as added value when you try their delicious and comprehensive all-in-one daily greens product.

This episode is brought to you by Levels! I wrote about the health benefits of using continuous glucose monitors (CGMs) more than ten years ago in The 4-Hour Body. At the time, CGMs were primitive and hard to use. Levels has now made this technology, and the unique insights that come from it, easy and available to everyone. Levels is making glucose monitoring simple, helping you see how food affects your health through real-time feedback. I started tracking my glucose years ago to learn more about what I should and shouldn’t be eating (including quantities, time of day, etc.), based on objective data from my own, unique physiology. Keeping my blood sugar stable is critical to my daily and long-term health and performance goals. Furthermore, poor glucose control is associated with a number of chronic conditions like diabetes, Alzheimer’s disease, heart disease, and obesity. It’s important.

If you’re interested in learning more about Levels and trying a CGM yourself, go to Levels.link/Tim.

Want to hear another podcast episode that explores the possibilities of rapamycin? Have a listen to the conversation I had with Peter Attia, David M. Sabatini, and Navdeep S. Chandel at the source of this miraculous compound: Easter Island. Here, we discuss how one of the most important discoveries of medical science was almost lost, why metabolism (along with longevity) research is key to treating a long list of diseases, intermittent dosing of rapamycin, parenting advice from scientists on confidence and conflict, the necessary failures of good science, good fonts versus bad fonts, “non-potato” relationships, and much more.

What was your favorite quote or lesson from this episode? Please let me know in the comments.

SCROLL BELOW FOR LINKS AND SHOW NOTES…

SELECTED LINKS FROM THE EPISODE

• Connect with Dr. Matt Kaeberlein:

Website | Twitter | LinkedIn

• Longer, Healthier Lives for All Dogs… And Their Humans | Dog Aging Project
• Understanding of the Biology of Aging | National Institute on Aging
• What is X-Ray Crystallography? | The Conversation
• Saccharomyces Cerevisiae | Wikipedia
• The Leonard Guarente Lab | MIT
• Western Washington University
• Minute to Understanding: Lifespan vs. Healthspan | The Jackson Laboratory
• Frozen Shoulder Symptoms and Causes | Mayo Clinic
• Rotator Cuff Injury Symptoms and Causes | Mayo Clinic
• Sterile Inflammation: Sensing and Reacting to Damage | Nature Reviews Immunology
• What Is Rapamycin? | New Scientist
• Senescent Cells: An Emerging Target for Diseases of Ageing | Nature Reviews Drug Discovery
• Apoptosis | National Human Genome Research Institute
• Inflammatory Cytokine | Wikipedia
• Senescence-Associated Secretory Phenotype | Wikipedia
• First Evidence That Senolytics Are Effective at Decreasing Senescent Cells in Humans | eBioMedicine
• My Life Extension Pilgrimage to Easter Island | The Tim Ferriss Show #193
• mTOR (Mammalian Target of Rapamycin) | Wikipedia
• The Peter Attia Drive Podcast
• Rapamycin Fights Gum Disease and Spurs Bone Growth in Older Mice | Dentistry Today
• How to Fight Sarcopenia (Muscle Loss Due to Aging) | Healthline
• The Reproductive Aging Conference | FASEB
• Sirolimus | MedlinePlus
• Lord of the Rings by J.R.R. Tolkien | Amazon
• Rapamycin and Alzheimer’s Disease: Time for a Clinical Trial? | Science Translational Medicine
• Rapamycin-Mediated Mouse Lifespan Extension: Late-Life Dosage Regimes with Sex-Specific Effects | Aging Cell
• Uncoupling Lifespan and Healthspan in Caenorhabditis Elegans Longevity Mutants | PNAS
• Calorie Restriction and Fasting Diets: What Do We Know? | National Institute on Aging
• Interventions Testing Program (ITP) | National Institute on Aging
• Acarbose | MedlinePlus
• Lifespan-Increasing Drug Nordihydroguaiaretic Acid Inhibits p300 and Activates Autophagy | NPJ Aging and Mechanisms of Disease
• Targeting Aging with Metformin (TAME) | American Federation for Aging Research
• What Is Alpha-Ketoglutarate? A Summary of AKG | Lifespan Extension Advocacy Foundation
• Spermidine: Autophagy & Anti-Aging Research | The Sheekey Science Show
• Nobel Prize for Research on the Cellular Recycling Program | Spermidine LIFE
• Higher Spermidine Intake Is Linked to Lower Mortality: A Prospective Population-Based Study | The American Journal of Clinical Nutrition
• Impact of the Natural Compound Urolithin A on Health, Disease, and Aging | Trends in Molecular Medicine
• Mitophagy: An Emerging Role in Aging and Age-Associated Diseases | Frontiers in Cell and Developmental Biology
• Male Lifespan Extension with 17‐α Estradiol Is Linked to a Sex‐Specific Metabolomic Response Modulated by Gonadal Hormones in Mice | Aging Cell
• Parkinson’s Drug Deprenyl Increases Lifespan in Rats | Longevity Technology
• Smart Drugs & Nutrients: How to Improve Your Memory and Increase Your Intelligence Using the Latest Discoveries in Neuroscience by Ward Dean and John Morgenthaler | Amazon
• The Significance of Selegiline/Deprenyl After 50 Years in Research and Therapy (1965–2015) | Molecular Psychiatry
• (Nicotinamide Adenine Dinucleotide) NAD⁺ Precursors | About NAD
• The 8 Most Popular Ways to Do a Low-Carb Diet | Healthline
• What Is Resistance Training and Why Is it Important? | Verywell Fit
• Dr. Andrew Huberman — A Neurobiologist on Optimizing Sleep, Enhancing Performance, Reducing Anxiety, Increasing Testosterone, and Using the Body to Control the Mind | The Tim Ferriss Show #521
• Study Finds Dogs Fed a Reduced-Calorie Diet Live Nearly Two Years Longer than Dogs on Unrestricted Diet | Penn Today
• Once-Daily Feeding Is Associated with Better Cognitive Function and Health in Companion Dogs: Results from the Dog Aging Project | GeroScience
• Saudi Government Begins Funding Longevity | Lifespan Extension Advocacy Foundation
• Hevolution Foundation
• “Cancer Was the Second Leading Cause of Death…” | Matt Kaeberlein, Twitter
• What is Geroscience? | American Federation for Aging Research
• Development & Approval Process for Drugs | FDA
• FDA Authorizes Marketing of the First Genetic Test to Aid in the Diagnosis of Fragile X Syndrome | FDA
• Here’s Why resTORbio Fell Over 83% Today | The Motley Fool
• Targeting the Biology of Ageing with mTOR Inhibitors to Improve Immune Function in Older Adults: Phase 2B and Phase 3 Randomised Trials | The Lancet Healthy Longevity
• The Gerontological Society of America
• Testing Positive for Sprinting | The Washington Post
• The Sixth Sense | Prime Video
• “Short-Lived Controls…” | Matt Kaeberlein, Twitter
• Studying Studies | Peter Attia
• Metformin | MedlinePlus
• NAD+ IV Therapy: All You Need to Know About NAD Infusion | Glendale, CA: Glendale Whole Health
• NMN vs. NR | NMN.com
• The SIR2/3/4 Complex and SIR2 Alone Promote Longevity in Saccharomyces Cerevisiae by Two Different Mechanisms | Genes Development
• Sirtuins, a Promising Target in Slowing Down the Ageing Process | Biogerontology
• Dr. Heidi Tissenbaum: Lessons From C. Elegans to Increase Healthspan | Longevity by Design
• Red Wine Ingredient Makes Yeast Live Longer | Nature
• Red Wine and Resveratrol: Good for Your Heart? | Mayo Clinic
• Sirtris Pharmaceuticals | Wikipedia
• Annual Meeting | American Aging Association
• Brian Kennedy
• Moiety (Chemistry) | Wikipedia
• The 4-Hour Body: An Uncommon Guide to Rapid Fat Loss, Incredible Sex, and Becoming Superhuman by Timothy Ferriss | Amazon
• Resveratrol Side Effects and Possible Health Dangers | Urology of Virginia
• Cherry Picking: When People Ignore Evidence that They Dislike | Effectiviology
• Centre for Ageing Research & Education (CARE)

SHOW NOTES

Note from the editor: Timestamps will be added shortly.

• What is aging biology?
• How Matt pivoted from mathematics to biology.
• What is the Dog Aging Project?
• Understanding healthspan through Matt’s frozen shoulder ordeal.
• Rapamycin vs. sterile inflammation.
• Current thoughts about how the immune system changes as we age.
• Anti-aging uses for rapamycin (and potential risks/side effects).
• Rapamycin and the Dog Aging Project.
• Rapamycin vs. neurodegeneration.
• What studies tell us about rapamycin’s potential to increase lifespan.
• Rapamycin alternatives considered for the Dog Aging Project.
• Urolithin A and spermidine.
• 17 alpha estradiol.
• Deprenyl.
• NAD precursors.
• What is Matt doing to increase his own lifespan/healthspan?
• Is time-restricted feeding beneficial for dogs?
• Currently, how well (or poorly) funded is longevity research?
• Where additional funding in this field would be best leveraged.
• Cutting through the hype and snake oil.
• Metformin.
• NAD infusion vs. natural NAD replenishment.
• Sirtuins.
• Resveratrol.
• Is there a fix to liability in defensive medicine?
• Finding better motivations for scientific pursuit.
• Longevity scientists worth checking out.
• Getting involved with the Dog Aging Project and parting thoughts.

MORE DR. MATT KAEBERLEIN QUOTES FROM THE INTERVIEW

“If you look at almost all of the major killers in developed countries, they all share a single greatest risk factor, and it’s how old you are. And that’s because of the underlying biology that creates a change in our physiology that is permissive for all of those diseases to happen.”
— Dr. Matt Kaeberlein

“We’ve got these misbehaving cells. They’re good-for-nothing, do-nothing cells that just kind of hang out and convince the other cells to do bad stuff. So if we could get rid of them, that’d be a good thing. It turns out it’s probably not that easy.”
— Dr. Matt Kaeberlein

“Being a dog guy and wanting my dog to live longer, when that light bulb went off in my head, I was like, ‘This goddamn has to happen.’”
— Dr. Matt Kaeberlein

“I constantly tell the people in my lab and other scientists, ‘You’ve got to do the experiment.’ You cannot go into it thinking that you know the answer and not do the experiment because your dogmatic belief says, ‘This is how it’s going to work.’ You’ve got to do the experiment.”
— Dr. Matt Kaeberlein

“People pay no attention to the psychological consequences that go along with trying to practice caloric restriction or trying to practice time-restricted feeding or intermittent fasting. I’m not saying they’re bad for everybody, but I know a lot of people who’ve dabbled with these things, and I would say some of the psychological effects aren’t great.”
— Dr. Matt Kaeberlein

“If you really could modulate the biology of aging, it will improve age-related immune function.”
— Dr. Matt Kaeberlein

“[Many] physicians . . . are very resistant to the idea of doing anything for somebody who’s not sick to keep them well. And we have to change that.”
— Dr. Matt Kaeberlein

PEOPLE MENTIONED

The Tim Ferriss Show is one of the most popular podcasts in the world with more than 800 million downloads. It has been selected for “Best of Apple Podcasts” three times, it is often the #1 interview podcast across all of Apple Podcasts, and it’s been ranked #1 out of 400,000+ podcasts on many occasions. To listen to any of the past episodes for free, check out this page.