The Life-Extension Episode — Dr. Matt Kaeberlein on The Dog Aging Project, Rapamycin, Metformin, Spermidine, NAD+ Precursors, Urolithin A, Acarbose, and Much More | 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.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!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 also 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 also 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.*[06:44] What is aging biology?[08:43] How Matt pivoted from mathematics to biology.[11:46] What is the Dog Aging Project?[13:42] Understanding healthspan through Matt’s frozen shoulder ordeal.[20:23] Rapamycin vs. sterile inflammation.[23:07] Current thoughts about how the immune system changes as we age.[29:11] Anti-aging uses for rapamycin (and potential risks/side effects).[42:20] Rapamycin and the Dog Aging Project.[45:30] Rapamycin vs. neurodegeneration.[48:21] What studies tell us about rapamycin’s potential to increase lifespan.[51:30] Rapamycin alternatives considered for the Dog Aging Project.[57:05] Urolithin A and spermidine.[59:45] 17 alpha estradiol.[1:01:47] Deprenyl.[1:03:54] NAD precursors.[1:05:52] What is Matt doing to increase his own lifespan/healthspan?[1:09:00] Is time-restricted feeding beneficial for dogs?[1:17:08] Currently, how well (or poorly) funded is longevity research?[1:22:02] Where additional funding in this field would be best leveraged.[1:35:19] Cutting through the hype and snake oil.[1:42:26] Metformin.[1:45:24] NAD infusion vs. natural NAD replenishment.[1:48:16] Sirtuins.[1:52:30] Resveratrol.[2:08:58] Is there a fix to liability in defensive medicine?[2:10:48] Finding better motivations for scientific pursuit.[2:15:48] Longevity scientists worth checking out.[2:17:39] Getting involved with the Dog Aging Project / parting thoughts.*For show notes and past guests on The Tim Ferriss Show, please visit tim.blog/podcast.For deals from sponsors of The Tim Ferriss Show, please visit tim.blog/podcast-sponsorsSign up for Tim’s email newsletter (5-Bullet Friday) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Discover Tim’s books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissYouTube: youtube.com/timferrissFacebook: facebook.com/timferriss LinkedIn: linkedin.com/in/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.
The Levels app uses glucose data to score your meals and provide insights on your food choices. With a team of expert advisors, including Dr. Dom DiAgostino, Levels is a top choice for personalized nutrition tracking.
Dr. Matt Kaeberlein discusses the difficulty of defining aging biology and the various levels of understanding it.
The Dog Aging Project is conducting a longitudinal study of aging in companion dogs to understand the genetic and environmental factors that affect biological aging in both dogs and humans, and to see if it is possible to slow or even reverse the aging process in dogs. The project aims to improve the health and longevity of companion dogs and provides insight into the mechanisms of aging in both dogs and people.
A discussion on dealing with age-related injuries and the potential decline of the immune system as we get older. The speaker shares personal experiences and the importance of finding the right treatment.
Rapamycin, a drug currently used as an immunosuppressant, has shown potential in rejuvenating the immune system in mice. Additionally, senescent cells, which can cause an immune system hyperactivation, are being studied as a possible target for anti-aging therapies.
Rapid Myosin treatment between four and 12 weeks can provide extensive benefits such as reversing periodontal disease, as proven through studies conducted on mice by different research labs.
Rapamycin, a drug commonly known for its use in organ transplant patients, has shown promise in reducing inflammation and improving oral health. Eight weeks of treatment has been shown to revert the oral microbiome back to a youthful state and promote bone growth around teeth.
Concerns on muscle loss related to rapamycin administration in mice were debunked by studies showing enhanced cognitive performance in treated mice. Research on the molecular level has shown different effects of rapamycin in other tissues.
Researchers have found rapamycin and caloric restriction to be the most effective interventions to delay declines in functions and diseases. While they can proportionately extend health span, it's questioned whether they extend life or just delay decline, and much longer, human lifespans could make the magnitude of the effect even smaller.
This podcast highlights some of the compounds that have extended lifespan and improved metabolic health in mice, including rapamycin and metformin.
This podcast episode discusses studies conducted on mice and dogs that demonstrated the lifespan extension effects of spermidine and Deprinil, and the potential benefits for age-related diseases.
The maintenance and increase of muscle mass is an important aspect of aging biology that often gets neglected in mainstream discussions. It's important to prioritize muscle mass for healthier aging.
A longitudinal study of the Dog Aging Project found that dogs who were fed once a day had a lower risk of disease than those who were fed more than once a day, making them a natural model for studying the effects of calorie restriction and alternative diets.
The psychological consequences of practicing caloric restriction, time-restricted feeding, or intermittent fasting are often overlooked in discussions of nutritional aging or longevity. While empirical evidence in humans is scant, these approaches' potential effects on animals suggest they may not be suitable for everyone, and sudden changes to feeding schedules may have negative effects on health and well-being.
The research on aging has been matured in the last two decades to the point where it should be funded equally with cancer research which has been getting funding for the last 50 years. Aging research should not be made fun of because it is merely behind cancer research by 50 years.
The development of clinically successful aging research drugs and subsequent human trials requires a much more significant focus on aging and drug trials in animals. The purpose being to gain substantial data that can result in substantial conclusions, instead of limited results from normal human clinical trials.
Periodontal disease is a great clinical trial endpoint as it shows relatively quick effects and is non-invasive. It could lead to FDA approval if an effect is found through clinical trials.
When conducting experiments with short-lived control groups, even a small effect size can be inflated, leading to an overestimation of results.
Experts are divided on whether non-diabetics should take metformin with some arguing that it would not make sense to take the drug if a person has a healthy lifestyle while others insist that it offers anti-aging benefits.
The sirtuins are important regulators of aging, and many studies have been conducted to prove their effectiveness in extending lifespan. Overexpressing the sirtuin gene in worms has been shown to extend their lifespan, leading to hundreds of millions of dollars spent on researching the effectiveness of sirtuins in mammals.
Researchers Brian Kennedy and the speaker tested the hypothesis that caloric restriction was working through SIR2 using resveratrol as a drug to activate SIR2 in yeast and exploring the possibility of it activating some proteins in the mammalian cell.
The efficacy of resveratrol and NAD in increasing lifespan is still not proven, but epidemiological studies suggest that mega dosing of resveratrol may have benefits for cardiovascular disease while NAD may result in a feeling of hyper caffeination but without its benefits.
A challenge for the field of bringing geroscience to clinical practice is that most physicians are trained to not treat healthy individuals. This mindset needs to shift to view aging as a precursor for disease and the importance of preventative measures in aging populations.
In this podcast conversation, the intersection of aging biology and disease is discussed, with a specific focus on geroscience and potential therapeutics through new science discoveries. The hosts also offer recommendations for further listening and discussion on the topic.
In this podcast episode, the host discusses various tech tricks, including a hormone called aldosterone, and shares a product called Element, formulated to help with electrolyte needs for those following a low carb or paleo diet.
Levels is an app that allows users to track their glucose levels after meals to determine their individual responses to different types of food. Users can learn what foods they should or shouldn't eat for optimal health.