#70 - David Sinclair, Ph.D.: How cellular reprogramming could slow our aging clock (and the latest research on NAD)
Play • 2 hr 10 min

In this episode, David Sinclair, Ph.D., a Professor in the Department of Genetics at Harvard Medical School and co-Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging, returns to the podcast to discuss the content of his new book, Lifespan: Why We Age - and Why We Don’t Have To. This conversation focuses on the biological mechanisms involved in what David terms the Information Theory of Aging which provides insights into the “clock” that determines our aging and to what degree it can be manipulated. Our discussion on aging of course leads us into interconnected topics of epigenetics, sirtuins, cellular senescence, as well as what compounds David is personally taking for his own longevity. Additionally, we discuss the most up to date information related to NAD and longevity by looking at the potential benefits (if any) of supplemental agents (NAD precursors, NR, NMR, etc.) that pose a promise of increasing NAD.

We discuss:

  • SIR genes and cellular identity [8:45];
  • Sirtuins regulate gene expression [14:30];
  • DNA is methylated at the deepest layer of the epigenome [17:45];
  • Methylation pattern and determining cellular age [20:15];
  • Cellular reprogramming [33:45];
  • Yamanaka factors to push cells "back in time”  [41:00];
  • Human cellular reprogramming viability [57:00];
  • Measuring the rate of aging [1:02:45];
  • Cellular reprogramming for longevity [1:14:45];
  • Compounds David takes for his own longevity [1:29:15]
  • NAD precursors (NR, NMN) and pterostilbene [1:40:00];
  • The current field of sirtuin activators [2:03:15];
  • David’s artistic work [2:05:15] and;
  • More.

Learn more: https://peterattiamd.com/ Show notes page for this episode:https://peterattiamd.com/davidsinclair2/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on Facebook | Twitter | Instagram.

ChooseFI
ChooseFI
The Unstuck Network
289 | The Roth 401K and Meal Planning Made Easy
* For almost 12 months, we've all been trying to do the best that we can. As frequently discussed on the show, we try to do things slightly different, optimize in the ways that we can, and make the best of the situation. * Jonathan's wife Dani has been coming up with all kinds of creative little activities for the kids. Even Jonathan was recruited for a rock painting project. * Brad has been listening to a new podcast, Ordinary Sherpa, created by Heidi, a member of Jonathan's Talent Stacker podcast. The podcast is about creating little adventures in life with your family. * At the same time, in the mastermind group Brad takes part in, he was inspired by a discussion related to dads really showing up to be a part of their kids' lives. * The podcast theme and mastermind group discussion converged for Brad when his daughter, Molly, asked him to go explore the creek with her. Rather than playing along for a minimally acceptable amount of time, Brad showed up like he really wanted to be there and they had hours of fun exploring together. * What if you started to show up for everything in your life with the attitude that you really wanted to be there? * It's difficult to be focused on growth in all areas of your life at the same time. There are different seasons when you will be able to lean into one over another but it's good to figure out a baseline you're comfortable with and recognize when it's time to rebalance. * Since Brad's financial life is on autopilot, it's not something he spends much time focusing on. However, sometimes things do backslide and he needs to return a little focus to it. Such as, he recently canceled two recurring charges for streaming services, not because their costs were going to have a significant impact, but because he was no longer getting value from them. * Relationships is an area Brad believes he could spend more time focusing on. If he were to ask himself, “Am I showing up as the best version of myself for my wife and kids every day?” his answer would be “no”. * Who should be leaning into and leveraging their Roth 401K? Sean Mullaney, The FI Tax Guy, says the Roth 401K works similar to a 401K except the funds going in are taxable today and come out later tax and penalty-free. * Those currently in a high tax bracket looking to retire early are probably better off contributing to a traditional 401K. But someone just out of college in a 10% federal tax bracket may benefit from paying 10% in taxes today rather than 20-30% later on. Even someone who may have substantial taxable income in retirement may benefit from a Roth 401K. * A Roth 401K can also be a hedge against future tax rates for anyone who prefers to lock in their tax rate today. * If your 401K plan offers it, you don't have to do all Roth 401K or traditional 401K. You can split the difference. * For example, a 60-year-old new retiree with a large 401K will be taxed on every dollar withdrawn. We don't know what future tax rates will be. * Roth 401K withdrawals don't work the same way as traditional 401K withdrawals. You can structure it in a way that you can recover tax-free contributions, From a Roth 401K, you may need to rollover into a Roth IRA. * For the early retirees who don't plan to retire at a super early age or anyone with artificially low income for a few years, the Roth 401K is a strategy to consider. * If you aren't 59 1/2 yet, Roth 401K withdrawals are subject to the cream in the coffee rule where 2/3 of the withdrawal is tax and penalty-free but 1/3 is subject to ordinary income tax and a penalty. This is different than a Roth IRA where contributions may be withdrawn at any age tax and penalty-free. * When you roll over a Roth 401K to a Roth IRA, the Roth 401K contributions go in as Roth IRA contributions, and earnings become Roth IRA earnings. You could then take out the full amount of contributions tax and penalty-free before touching the earnings. * If you aren't 59 1/2 and need to access your Roth 401 contributions, it makes sense to roll them over to a Roth IRA first. * If you have employer stock in your 401K, there may be net unrealized appreciation. You do not want to roll it over from a traditional 401K to a traditional IRA without considering a tax planning strategy. This requires assistance from a tax professional. * If you want to do a backdoor Roth IRA, rolling over 401K to a traditional IRA isn't a good idea. * The fees associated with 401K plans have gotten better over the last 10-15 years. The investment choices are better with lower fees. It may not make sense to do a rollover. * As a general rule, retirement accounts have required minimum distributions (RMDs) once you turn age 72. The exception is the Roth IRA. While RMDs from a Roth 401K are not taxable, you want to keep that money growing tax-free as long as possible for you and your heirs. If you're 72, Sean would recommend you roll your Roth 401K to a Roth IRA for that reason. * Generally, you need a separation of service to do rollovers from a Roth 401K to a Roth IRA. Look for your plan's Summary Plan Description (SPD) which details withdrawals. * 401K plans are subject to the ERISA law, where creditors cannot access the funds, except for ex-spouses and the IRS. IRA creditor protection varies from state to state. Something to consider before a rollover. * Dani and the ChooseFI Foundation are using meal planning as a financial literacy tool. Always looking for ways to get children interested and thinking bout decision-making and personal finance, they have put together Meal Planning Made Easy. * The meal planning project helps kids put financial literacy concepts into a real-world contest. The goal is to make financial literacy concepts more than just habits but to have kids take ownership and have fun doing it. * In the 3rd through 5th-grade video series, Dani talks them through meal planning. They are tasked with going into a grocery store, either in-person or virtually, and planning all three meals for one day. * The meal planning project is adaptable to fit every socioeconomic setting. * The tasks grow as children develop. High school students may plan meals for an entire week, searching the pantry first, and finding recipes to help on the budgeting side of things, just like parents have to do. * Sign up for Meal Planning Made Easy at Choosefi.com/mealplan. Resources Mentioned In Today's Conversation * The FI Tax Guy * Ordinary Sherpa * Do Inner Work * Roth 401K Withdrawals * ChooseFI Foundation * ChooseFI.com/mealplan * Get started on your own journey to financial independence at ChooseFI.com/start. If You Want To Support ChooseFI: * Earn $1,000 in cashback with ChooseFI's 3-card credit card strategy.  * Share FI by sending a friend ChooseFI: Your Blueprint to Financial Independence.
59 min
STEM-Talk
STEM-Talk
Dawn Kernagis and Ken Ford
Episode 117: Julie Anderson talks about her research into aging and neurodegenerative diseases
Our guest today is Dr. Julie Andersen, who is best known for her research into aging and age-related diseases. A professor at the Buck Institute Buck Institute for Research on Aging, an independent biomedical research institute that researches ways to extend the healthy years of life, Julie and her colleagues at Buck have focused on understanding the underlying age-related processes driving neurodegenerative diseases in order to identify novel therapeutics. Because our conversation with Julie was so fascinating and long, we have divided it into two parts. In today’s part one of her interview, we talk to Julie about her youth and early career. We also talk to her about the potential of of rapamycin to protect brain cells and mitochondria in a mouse model of Parkinson’s disease as well as her thoughts about the Amyloid Cascade Hypothesis. In part two, which will go live in a few weeks, we have an in-depth conversation with Julie about her research into the neuroprotective properties of urolithin A. In terms of Julie’s background, she received her Ph.D. from UCLA and did her post-doc in the department of neurology at Harvard. In 2000 Julie joined the Buck Institute. Show notes: [00:03:33] Dawn opens the interview asking if it is true that Julie was a quiet kid who normally sat in the back of the classroom. [00:03:52] Dawn mentions that Julie was born in Montana but that she grew up in northern Idaho. Dawn asks what it was that brought Julie’s family to Idaho. [00:04:29] Dawn asks Julie what interests she had growing up. [00:05:05] Ken remarks on the fact that one of Julie’s favorite books is a biography of Clementine, Winston Churchill’s wife, and asks where Julie’s interest in Clementine came from. [00:05:46] Dawn mentions that for Julie’s undergraduate degree, she went to Washington State University, where her father was a professor. Dawn asks if Julie knew from the start that she was going to focus her undergraduate studies on plant physiology. [00:07:03] Ken asks Julie took her to UCLA for her Ph.D. [00:08:16] Dawn asks Julie what led to travel across the country to Boston for her post-doc. [00:09:26] Julie explains why she eventually returned to California after her Ph.D. [00:11:32] Dawn asks Julie to tell the story of how meeting someone she described as “a fellow nerd” at an aging conference eventually led her to taking a position at the Buck Institute. [00:14:34] Ken remarks that Julie must like working at the Buck, given she has remained there for the last 20 years. Julie describes what is it about the Buck Institute that makes it such a special place. [00:17:51] Dawn mentions that for the past 20 years, Julie and her lab at Buck have looked at a lot of different aspects of neurodegeneration, with a heavier concentration on autophagy in the past five years. Dawn goes on to mention that Julie has especially been investigating a natural bioactive known as urolithin A. Before diving into all of this work specifically, Dawn asks Julie, what drew her to the study of neurodegeneration to begin with. [00:19:55] Ken asks what prompted Julie’s current focus on autophagy. [00:24:11] Dawn explains that degradation of damaged mitochondria via lysosomal autophagy is a key cellular pathway in the maintenance of mitochondrial homeostasis.  Disruption of this pathway contributes to the progressive cell loss that is associated with Parkinson’s disease. She goes on to mention that Julie published the results of a study in 2015that found rapamycin can protect brain cells and mitochondria in a mouse model of Parkinson’s disease. Julie explains the significance of this study and talks about the importance of rapamycin in the research of therapies for Parkinson’s disease. [00:30:44] Dawn asks Julie to explain the concept, and the significance of, transcription factor EB (TFEB), which is a protein that is encoded in humans by the TFEB gene, and is a master regulator of autophagy and lysosom...
50 min
The Future of Life
The Future of Life
Future of Life Institute
Beatrice Fihn on the Total Elimination of Nuclear Weapons
Beatrice Fihn, executive director of the International Campaign to Abolish Nuclear Weapons (ICAN) and Nobel Peace Prize recipient, joins us to discuss the current risks of nuclear war, policies that can reduce the risks of nuclear conflict, and how to move towards a nuclear weapons free world. Topics discussed in this episode include: -The current nuclear weapons geopolitical situation -The risks and mechanics of accidental and intentional nuclear war -Policy proposals for reducing the risks of nuclear war -Deterrence theory -The Treaty on the Prohibition of Nuclear Weapons -Working towards the total elimination of nuclear weapons You can find the page for this podcast here: https://futureoflife.org/2021/01/21/beatrice-fihn-on-the-total-elimination-of-nuclear-weapons/ Timestamps:  0:00 Intro 4:28 Overview of the current nuclear weapons situation 6:47 The 9 nuclear weapons states, and accidental and intentional nuclear war 9:27 Accidental nuclear war and human systems 12:08 The risks of nuclear war in 2021 and nuclear stability 17:49 Toxic personalities and the human component of nuclear weapons 23:23 Policy proposals for reducing the risk of nuclear war 23:55 New START Treaty 25:42 What does it mean to maintain credible deterrence 26:45 ICAN and working on the Treaty on the Prohibition of Nuclear Weapons 28:00 Deterrence theoretic arguments for nuclear weapons 32:36 The reduction of nuclear weapons, no first use, removing ground based missile systems, removing hair-trigger alert, removing presidential authority to use nuclear weapons 39:13 Arguments for and against nuclear risk reduction policy proposals 46:02 Moving all of the United State's nuclear weapons to bombers and nuclear submarines 48:27 Working towards and the theory of the total elimination of nuclear weapons 1:11:40 The value of the Treaty on the Prohibition of Nuclear Weapons 1:14:26 Elevating activism around nuclear weapons and messaging more skillfully 1:15:40 What the public needs to understand about nuclear weapons 1:16:35 World leaders' views of the treaty 1:17:15 How to get involved This podcast is possible because of the support of listeners like you. If you found this conversation to be meaningful or valuable, consider supporting it directly by donating at futureoflife.org/donate. Contributions like yours make these conversations possible.
1 hr 18 min
The Daily Stoic
The Daily Stoic
Daily Stoic
How the Stoics Can Make You A Better Leader
The Stoics have many lessons to share about leadership. From Marcus Aurelius' reflections on his rule as the Emperor of Rome, to Epictetus' experiences as a slave, the Stoics are uniquely positioned to discuss leadership and how to approach it. On today’s podcast, Ryan discusses the Stoic principles that can improve your role as a leader, no matter what you do. This episode is brought to you by GiveWell, the best site for figuring out how and where to donate your money to have the greatest impact. GiveWell’s team of researchers works countless hours to determine which charities make the most effective dollar-for-dollar contributions to the causes they support. Since 2010, GiveWell has helped over 50,000 donors donate over 500 million dollars to the most effective charities, leading to over 75,000 lives saved and millions more improved. Visit GiveWell.org/stoic and your first donation will be matched up to 100 dollars. This episode is also brought to you by ExpressVPN, the #1 worldwide VPN. ExpressVPN has super-fast connection speeds and keeps your data safe. No more advertisers selling your info for a quick buck, no more downloads at a snail’s pace. Sign up now at ExpressVPN.com/STOIC and get an extra three months on your one-year package, absolutely free. *** If you enjoyed this week’s podcast, we’d love for you to leave a review on Apple Podcasts. It helps with our visibility, and the more people listen to the podcast, the more we can invest into it and make it even better. Sign up for the Daily Stoic email: http://DailyStoic.com/signup Follow @DailyStoic: Twitter: https://twitter.com/dailystoic Instagram: https://www.instagram.com/dailystoic/ Facebook: http://facebook.com/dailystoic YouTube: https://www.youtube.com/dailystoic
14 min
THE INTELLECTUAL DARK WEB PODCAST (HOBBES + LOCKE + ROUSSEAU + US CONSTITUTION in ONE BOOK for 29$)
THE INTELLECTUAL DARK WEB PODCAST (HOBBES + LOCKE + ROUSSEAU + US CONSTITUTION in ONE BOOK for 29$)
Intellectual Dark Web Podcast
Isaiah Berlin - The Significance of Philosophy - Isaiah Berlin & Bryan Magee Clips
Isaiah Berlin - The Significance of Philosophy - Isaiah Berlin & Bryan Magee Clips ISAIAH BERLIN TALK  THE INTELLECTUAL DARK WEB PODCAST We Search the Web for the Best Intellectual Dark Web Podcasts, Lectures and Videos that can be understood by merely listening to save YOUR time. Then we make those Intellectual Dark Web Episodes available on Spotify and downloadable. IMPORTANT! AMAZON DELETED THE LAST INEXPENSIVE BINDING. IT WAS TOO CHEAP! HERE IS ANOTHER VERSION FOR STUDENTS WITH HOBBES, LOCKE, ROUSSEAU AND THE US CONST. IN ONE BOOK: ||| MACHIAVELLI https://www.lulu.com/en/us/shop/niccolo-machiavelli-and-john-locke-and-thomas-hobbes-and-peter-kanzler/the-leviathan-1651-the-two-treatises-of-government-1689-and-the-constitution-of-pennsylvania-1776/paperback/product-69m6we.html XXX https://www.bookfinder.com/search/?author=peter%2Bkanzler&title=pennsylvania%2Bconstitution%2Bleviathan&lang=en&isbn=9781716844508&new_used=N&destination=us&currency=USD&mode=basic&st=sr&ac=qr || ROUSSEAU https://www.lulu.com/en/us/shop/jean-jacques-rousseau-and-thomas-hobbes-and-john-locke-and-peter-kanzler/the-leviathan-1651-the-two-treatises-of-government-1689-the-social-contract-1762-the-constitution-of-pennsylvania-1776/paperback/product-782nvr.html XXX https://www.bookfinder.com/search/?author=peter%2Bkanzler&title=pennsylvania%2Bconstitution%2Bleviathan&lang=en&isbn=9781716893407&new_used=N&destination=us&currency=USD&mode=basic&st=sr&ac=qr | Thank You Dearly For ANY Support! And God Bless You.
8 min
The Rich Roll Podcast
The Rich Roll Podcast
Rich Roll
Mastering The Microbiome
Our bodies are comprised of about ten trillion cells. But only half those cells are human. The remainder comprise our microbiome—a vast and complex ecosystem of bacteria, viruses, and fungi that live in or on our bodies. Only now is science beginning to understand the profound impact of these microbes on human health. We choose to believe that we are fully sentient and self-governing, wholly responsible for our health, moods and decisions. But the truth is far different. In fact, to a large extent, our emotional state, propensity for disease, the nature of our cravings, and even some of our decision making can be traced back to the nature of our gut ecology. Most of these microorganisms are symbiotic. Maintaining a healthy culture of the right microorganisms is fundamental to good health. But should the quality of your microbiome go awry, health havoc ensues. To better understand the vital role these microorganisms play in our health and lives, today’s show is a veritable microbiome masterclass courtesy of the gastroenterologists, scientific researchers, and gut experts that have graced the show over the years. After 8+ years and 500+ conversations, I’ve compiled a vast library of bankable, timeless information and advice. As a steward of this archive, I feel a responsibility to convert the best of it into a more helpful, productive, accessible, and practical resource. As an initial step toward this goal, I will be periodically offering curated wisdom focused on a specific theme or subject (as opposed to a guest). This episode is an embryonic experiment in doing just that—the first in what will be an evolving series of deep dives, commencing with this microbiome intensive courtesy of the following collection of past podcast gut health expert guests (all hyperlinked to their respective full episodes): * Robynne Chutkan, M.D. * Ara Katz and Raja Dhir * Zach Bush, M.D. * Rhonda Patrick, Ph.D. * Will Bulsiewicz, M.D. The visually inclined can watch it unfold on YouTube. And as always, the podcast streams wild and free on Apple Podcasts and Spotify. I sincerely hope you find this experiment helpful and instructive. Peace + Plants, Listen, Watch & Subscribe Apple Podcasts | YouTube | Spotify | Stitcher | Google Podcasts Thanks to this week’s sponsors: Calm: The app designed to help you ease stress and get the best sleep of your life with guided meditations, sleep stories, and more. Right now, my listeners can get a special limited-time promotion of 40% off a Calm Premium subscription at calm.com/richroll. It includes unlimited access to ALL of Calm’s amazing content. Get started today! Four Sigmatic: Nutritious and delicious mushroom brews and elixirs made with only the highest quality adaptogens and easy to take on the go. To try ‘em out visit foursigmatic.com/roll and use the discount code ROLL to get 10% off your order. Public Goods: One version of every essential in one place. Healthy, high quality, sustainable and affordable home goods, personal care products, and premium pantry staples. Everything is ethically sourced and free of harmful additives. The folks at Public Goods are generously giving listeners of the show $15 to spend on their first purchase — just go to publicgoods.com/RICHROLL or use code RICHROLL at checkout. Outerknown: Founded by pro-surfer Kelly Slater, Outerknown creates high quality, sustainably produced, and great looking men’s and women’s clothes, ethically manufactured in the world’s cleanest solar-powered factory. When you’re ready to amp up your wardrobe with awesome sustainable duds, go to outerknown.com and enter my code ROLL at checkout to get 25% off your full-price order. SHOW NOTES: Guests featured in this episode (all hyperlinked to their respective episodes) include: * Robynne Chutkan, M.D. * Ara Katz and Raja Dhir * Zach Bush, M.D. * Rhonda Patrick, Ph.D. * Will Bulsiewicz, M.D. I'm proud to announce my new book 'Voicing Change'. To learn more & pre-order now, visit, richroll.com/vc There are a few simple ways you can support the show and the content we strive to craft and share every single week Subscribe & Review: Please make sure to review, share comments and subscribe to the show on the various platforms (Apple Podcasts, YouTube & Spotify). This helps tremendously! Patronize Our Sponsors: Supporting the companies that support the show! For a complete list of all RRP sponsors and their respective vanity URLs and discount codes, click the ‘Sponsors’ tab in the ‘Shop’ menu. Spread The Word: Help grow our reach by sharing your enthusiasm for the podcast and/or your favorite episodes by posting about it on social media. Thank The Team: I do not do this alone. Send your love to Jason Camiolo for production, audio engineering and show notes; Margo Lubin and Blake Curtis for video, editing and graphics; portraits by Ali Rogers & Davy Greenberg; and theme music by Tyler Piatt. Trapper Piatt & Hari Mathis. See acast.com/privacy for privacy and opt-out information.
1 hr 24 min
COMPLEXITY
COMPLEXITY
Santa Fe Institute, Michael Garfield
Cris Moore on Algorithmic Justice & The Physics of Inference
It’s tempting to believe that people can outsource decisions to machines — that algorithms are objective, and it’s easier and fairer to dump the burden on them. But convenience conceals the complicated truth: when lives are made or broken by AI, we need transparency about the way we ask computers questions, and we need to understand what kinds of problems they’re not suited for. Sometimes we may be using the wrong models, and sometimes even great models fail when fed sparse or noisy data. Applying physics insights to the practical concerns of what an algorithm can and cannot do, scientists find points at which questions suddenly become unanswerable. Even with access to great data, not everything’s an optimization problem: there may be more than one right answer. Ultimately, it is crucial that we understand the limits of the technology we leverage to help us navigate our complex world — and the values that (often invisibly) determine how we use it. Welcome to COMPLEXITY, the official podcast of the Santa Fe Institute. I’m your host, Michael Garfield, and every other week we’ll bring you with us for far-ranging conversations with our worldwide network of rigorous researchers developing new frameworks to explain the deepest mysteries of the universe. We kick off 2021 with SFI Resident Professor Cristopher Moore, who has written over 150 papers at the boundary between physics and computer science, to talk about his work in the physics of inference and with The Algorithmic Justice Project. If you value our research and communication efforts, please consider making a donation at santafe.edu/give — and/or rating and reviewing us at Apple Podcasts. You can find numerous other ways to engage with us at santafe.edu/engage. Thank you for listening! Join our Facebook discussion group to meet like minds and talk about each episode. Podcast theme music by Mitch Mignano. Follow us on social media: Twitter • YouTube • Facebook • Instagram • LinkedIn Related Reading: Cris Moore’s Google Scholar Page The Algorithmic Justice Project “The Computer Science and Physics of Community Detection: Landscapes, Phase Transitions, and Hardness" _The Ethical Algorithm _by SFI External Professor Michael Kearns “Prevalence-induced concept change in human judgment” co-authored by SFI External Professor Thalia Wheatley “The Uncertainty Principle” with SFI Miller Scholar John Kaag SFI External Professor Andreas Wagner on play as a form of noise generation that can knock an inference algorithm off false endpoints/local optima Related Videos: Cris Moore’s ICTS Turing Talks on “Complexities, phase transitions, and inference” Fairness, Accountability, and Transparency: Lessons from predictive models in criminal justice Reckoning and Judgment The Promise of AI Easy, Hard, and Impossible Problems: The Limits of Computation. Ulam Memorial Lecture #1. Data, Algorithms, Justice, and Fairness. Ulam Memorial Lecture #2. Related Podcasts: Fighting Hate Speech with AI & Social Science (with Joshua Garland, Mirta Galesic, and Keyan Ghazi-Zahedi) Better Scientific Modeling for Ecological & Social Justice with David Krakauer (Transmission Series Ep. 7) Embracing Complexity for Systemic Interventions with David Krakauer (Transmission Series Ep. 5) Rajiv Sethi on Stereotypes, Crime, and The Pursuit of Justice
1 hr 12 min
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