In this twenty-first episode, Nichola Conlon provides a scientific background, introducing sirtuins and NAD. She then explains why popular NAD+ boosters, NR and NMN, are first-gen products. Read the transcript She details how Nuchido formulated the first second-gen product by taking a novel whole systems approach. Lots of NAD, anti-aging, and nutraceutical discussion along the way. Topics we discussed in this episode Recent personal experience with COVID-19 Her molecular biology PhD focus Systems pharmacology Help from Aubrey de Gray Disillusioned with drug development Founding Nuchido What are Sirtuins? What is NAD? Importance of NAD. Why Boost NAD Levels? Inefficiency of First-Gen NAD Supplements: NR and NMN Three ingredients to boost NAD Pure NAD limitations Nicotinamide Riboside (NR) Nicotinamide Mononucleotide (NMN) 60% increase in NAD "only" Second-gen, demonstrated it can be done much better if you take a whole systems approach Importance of NAD salvage pathway PARP enzymes Inability to power sustained high-levels because of salvage pathway deterioration First-gen may not be great for epigenetics Increases expression of the enzymes in the salvage pathway that are known to decline with age Ingredients that reduce the expression of other processes that are actually wasting NAD Enzyme called CD38 Inflammatory levels - CD38 just chews up NAD Multiple things that you can do to fix the cell before you even need to put precursors in. NAD decreases with age Do we Need NAD Supplements? Sirtuins and mitochondrial biogenesis Boosting your NAD levels, improves mitochondrial function. Multiple reasons that are causing the NAD to decline, boosting as with first-gen only the amount of raw material that your cell has is quite naïve Second-gen helps fixe your body's natural ability to make and recycle its own NAD Nuchido TIME+ boosts NAD on average by 242%, four times more than the 60% widely cited for first-gen ChromaDex vs Elyisum Health Terms B3, niacin, nicotinamide, nicotinic acid, NR Abram Hoffer and orthomolecular medicine Nicotinamide is not likely to be a sirtuin inhibitor, How to measure NAD levels Nuchido TIME+ ingredients Alpha lipoic acid (ALA) and effects on AMPK Conversion of NADH to NAD+ Drift more towards having more NADH in your cell with age Pathway called NQO1, converts NADH back to NAD+ ALA is a really powerful antioxidant, activates NRF2 ALA vs ALA-R Sophora Japonica Extract Rutin, senolytic NAMP Aging is an inflicted cascade disorder Show links Nuchido (Company Website) ChromaDex (Company Website) Elysium Health (Company Website) Elysium Health, Inc. Loses Appeal of Patent Challenge Decision (Press Release) Orthomolecular Medicine (Wikipedia Entry) Abram Hoffer (Wikipedia Entry) Niacin: The Real Story: Learn about the Wonderful Healing Properties of Niacin (Amazon, Book) Orthomolecular Medicine for Everyone (Amazon, Book) GlycanAge (Company Website)

In this twentieth episode, Polina Mamoshina introduces recently launched Deep Longevity, and its app (young.ai). Read the transcript Biomarkers of aging are introduced. She explains that they have taken a superior approach by using deep learning instead of machine learning. Aging clocks in general are covered. Finally, she shares her view that transcriptomic and proteonomic clocks are the likely future. Topics we discussed in this episode Personal background: Moscow State University, Oxford University, Insilico Medicine hackathon Bringing Deep Longevity out of stealth, Young.ai companion app Deep Longevity introduction including company aims Description of Young.AI app Biomarkers of aging as the accelerant of market for aging interventions Introduction to aging clocks: Horvath, Hannum Taking a novel and superior technological approach to aging clocks, using deep neural networks, instead of shallow machine learning Limitations of shallow machine learning models Ability of neural networks to capture highly non linear dependencies and what that matters for biological age determination Investing in anticipated payoff from deep learning over the long-term, even if machine learning may be good enough in many cases now Biological age prediction with Aging.ai Two approaches to designing aging clocks Machine learned PhenoAge biological age score Introducing mortality, with the GrimAge score Longevity clinics and life insurance as market Biological age scoring as onboarding tool for life insurance markets Training datasets Common blood analytes used in PhenoAge vs Aging.ai Optimized blood analyte levels for a given individual to get younger Orthodox medicine uses blood analyte levels that are not specific to the individual and not optimized ranges; designed to detect only late-stage pathologies Cheapness of regular blood analytes Emerging market is likely to age score bodily subsystems rather than provide an overall singular biological age score Goal is to find the fastest ticking clock in your body Biological age test using a selfie Providing a library of biological age scores, from free to expensive, so users can upgrade, find out more about themselves Belief that proteomic and transcriptomic clocks will outperform epigenetic clocks in terms of being actionable with interventions Epigenetics and aging Acceleration of the aging rate may show up "late" in terms of being able to intervene, on the epigenome Youthful blood plasma exchanges and age quantification Transcriptomic, proteomic, and glycomic clocks Anticipated rise of longevity clinics Show links Deep Longevity (Company Website) Insilico Medicine (Company Website) Human Longevity, Inc. (Company Website) Regent Pacific Group (Company Website) Young.AI (App from Deep Longevity) Aging.AI (Biological Age Prediction) 'DNA Methylation Age of Human Tissues and Cell Types' (Paper) 'Assessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research' (Paper) Steve Horvath (WikiPedia Entry) 'Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates' (Paper) Gregory Hannum (LinkedIn) Morgan Levine (LinkedIn) 'An epigenetic biomarker of aging for lifespan and healthspan' (Paper) Elysium Health (Company Website) 'DNA Methylation GrimAge Strongly Predicts Lifespan and Healthspan' (Paper) FOXO BioScience (Company Website) NHANES III (CDC) AgeoTypes (Stanford Article) GlycanAge (Company Website) GENOS (Company Website)

In this nineteenth episode, Stephen Matlin introduces telomere biology. He details how testing services typically use Q-PCR which provides an average telomere length and why that doesn't really mean anything. Read the transcript Instead the percentage of critically-short, measured using Q-FISH, does. Finally he chats about supplements - telomerase inducers - for growth. Topics we discussed in this episode Introduction to telomere biology Hayflick limit, senescent cells, apoptosis Telomeres and the hallmarks of aging Quantitative PCR derived average telomere length vs shortest telomeres Coefficient of variation of lab samples Role of supplements in supporting our telomeres and overall biological function Declining nutrition in even vegetables Telomerase inducers TA-65 and TAM-818 Telomerase enzyme Henrietta Lacks cells, cancer and the Hayflick limit Telomerase supplements and cancer Telomerase inducer Telomere Benefits™ Providing biological age scores using telomere measurements Telomere length and correlation with healthspan Improving upon biomarker Prostate Specific Antigen with Prostate Telomere Associate Variance Show links LifeLength.com (Company Website) T.A. Sciences TA-65 (UK/Europe) T.A. Sciences TA-65 (Amazon.com) Hayflick, His Limit, and Cellular Ageing (Paper) The Hayflick Limit (Embryo Project Encyclopedia) The End-Replication Problem (Paper) Leucocyte Telomere Length And Risk Of Cardiovascular Disease: Systematic Review And Meta-analysis (Paper) Association Between Leucocyte Telomere Length And Cardiovascular Disease In A Large General Population In The United States (Paper) The Hallmarks of Aging (Paper) Coefficient of Variation (Wikipedia Entry) A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study (Paper) The Telomerase Activator Ta-65 Elongates Short Telomeres And Increases Health Span Of Adult/old Mice Without Increasing Cancer Incidence (Paper) Discovery Of Potent Telomerase Activators: Unfolding New Therapeutic And Anti-aging Perspectives (Paper) The Nobel Prize in Physiology or Medicine 2009 (Website) Defy Time (Website) Telomere Benefits™ (Product Link) Mathematical Connection Between Short Telomere Induced Senescence Calculation And Mortality Rate Data (Paper) Comparison Of Telomere Length Measurement Methods (Paper) Beyond Average: Potential For Measurement Of Short Telomeres (Paper)

In this eighteenth episode, Alexis Shields explains that blood biomarkers may be obtained directly and the results used to reduce chance of future disease occurrence, as well as remedy any subclinical symptoms. Read the transcript She provides a tour of some of the common biomarkers. Along the way she describes her virtual functional medicine practice. Topics we discussed in this episode Terms naturopathic, homeopathic, allopathic and functional medicine Urine biomarkers, DUTCH test Triglyceride to HDL ratio correlates with cardiovascular disease, heart disease, and diabetes Thyroid testing and Reverse T3 Thyroid and low mineral status Hashimoto's disease and hypothyroidism Hematology testing Machine learning tool for looking at blood work Iron vs ferritin Iron levels Cholesterol testing High-resolution lipid analysis LDL, nor total cholesterol has much predictive power Apolipoprotein B (ApoB) and Lipoprotein(a) Cholesterol and immunity Adrenal testing Sodium and potassium levels and adrenal dysfunction Cortisol testing Urine testing of pH is really tricky Dietary cholesterol has minimal impact on blood cholesterol levels Electrolytes and diet Body acidity and disease Insulin resistance Physiological insulin resistance Glucose and melatonin Blood tests and supplements with COVID-19 in mind Show links DrAlexisShields.com (Website) Stop Flushing Terabytes of Data Down the Toilet – (EP11: Daniel Maggs, bisu) Nordic Labs (Website) TG:HDL – Heart Disease Risk Calculator (Online Tool) KSM-66 Ashwagandha Extract (Website) Rhodiola Rosea (Website) Hormesis (Wikipedia Entry) Lymphocytes Definition (Article) Leukocytes Definition (Article) Neutrophils Definition (Article) BloodSmart.ai (Website) C-Reactive Protein (Article) LIPOPRINT LDL Subfractions Test (Website) NMR Lipid Profile (Article) DUTCH Test (Website) Anion Gap (Wikipedia Entry) HOMA-IR Calculator (Web Page)

In this seventeenth episode, Gordon Lauc introduces glycobiology. He details GlycanAge®, the world’s first direct-to-consumer glycan-based product. Read the transcript He explains that it can quantify how well interventions (e.g. supplements) work for you as an individual, and how much healthy life you’ve got left. Finally he details a potential COVID-19 glycan biomarker to accurately assess your risk. Topics we discussed in this episode [coming soon] Show links [more links coming soon] GlycanAge (Website) Genos (Website)

In this sixteenth episode, Knut Wittkowski shares his expert view that lockdowns were not necessary. That he can’t figure out a single justification for extending them. That there is no “second wave”. That there is no viable option other than herd immunity, and that by prolonging the pandemic, we are putting the vulnerable at greater risk.

In this fifteenth episode, Liz Parrish shares her quest for radical life extension and details her two completed gene therapies. Read the transcript She describes the regenerative medical tourism available today for increased lifespan and costs. She relates her company's mission to create a human that regenerates faster than they degenerate. She details her upcoming gene therapies, including upgraded IQ. Topics we discussed in this episode Making controversial medical history Quest for radically increased longevity Upregulating telomerase, hTERT Downregulates myostatin, follistatin Interest in regenerative medicine technologies Desire to help billions of people Comany goal to create a human that regenerates faster than they degenerate PGC-1α BioViva's DNA methylation kit Plan to look at multiple aging clocks Regenerative medical tourism Childhood ambition Space travel and gene therapy are intertwined Personal goals Morphological freedom Hope for the future Being of optimistic nature Gene therapy - dystopian or utopian? Gene therapy costs Societal health stratification Making humans more malleable like software What is gene therapy? Gene delivery and viral vectors Next personal gene therapy - Klotho Next personal gene therapy - PGC-1α Developing New Viral Vectors Apo-A1 Milano Adeno-Associated Virus (AVV. AAV-2) Show links BioViva (Website) Integrated Health Systems (Website) Telomeres and Longevity: A Cause or an Effect? (Paper) Effects of Myostatin Deletion in Aging Mice (Paper) Telomeres and Telomerase as Therapeutic Targets to Prevent and Treat Age-Related Diseases (Paper) Inhibition Of Myostatin With Emphasis On Follistatin As A Therapy For Muscle Disease (Paper) PGC-1α in Aging and Anti-Aging Interventions (Paper) TimeKeeper™ DNA Methylation kit (Landing Page) Longevity (Subreddit) Maximum Life Foundation (Website) George Church (Wikipedia Entry) Factor IX (Wikipedia Entry) hTERT (Wikipedia Entry) Hayflick Limit (Wikipedia Entry) Follistatin (Wikipedia Entry) The Longevity Hormone Klotho Is a New Player in the Interacion of the Growth Hormone/Insulin-Like Growth Factor 1 Axis (Paper) rs9536314/Klotho Gene (SNPedia Entry) PGC-1α in Aging and Anti-Aging Interventions (Paper) María A. Blasco (University Staff Page) The Long Saga of Apo-A1 Milano (Article) Why Most Published Research Findings Are False (Paper)

In this fourteenth episode, Dr. William Davis shares his view that healthcare is not primarily concerned with our health. Instead it is concerned with profit, even at the expense of our health. Read the transcript He explains that the best way to protect our health and our finances from healthcare is to take our health under our control. And in doing so we can achieve “magnificent health”. Topics we discussed in this episode Healthcare system primary focus on profit, not your health The more you spend on healthcare, the more the mortality rate goes up Addressing factors that allow disease to emerge in the first place Healthcare may make you sicker and fatter "Magnificent health" is achievable with little to no drugs A long-term ketogenic diet has negative effects on gut microbiome composition Vitamin D and magnesium deficiency Disrupted gut microbiome composition factors Small Intestinal Bacteria Overgrowth (SIBO) SIBO link to rheumatoid arthritis, fibromyalgia, polymyalgia rheumatica, Hashimoto’s thyroiditis, Parkinsonism, Alzheimer’s dementia Lactobacillus reuteri DSM 17938 Lactobacillus reuteri ATCC PTA 6475 Grain elimination to avoid zinc deficiency Lactobacillus casei Lactobacillus rhamnosus GG Bifidobacterium Longum Akkermansia Muciniphila Stopping or reversing coronary atherosclerosis CT heart scanning NMR lipoprotein testing What foods cause harmful LDL-Cholesterol particles Lipoprotein(a) Thyroid tests A1C test LIPOPRINT high-resolution cholesterol test Corrupt JUPITER study Magnesium water Need for iodine; kelp Vitamin K2 Show links Wheat Belly Blog (Website) Undoctored (Website) AIRE device (Website) Small Intestinal Bacteria Overgrowth (SIBO) Test (Website) "Leaky Gut Syndrome" (NHS Article) Triage Theory of Aging (YouTube Video) The Unique Probiotic Benefits of L Reuteri Yogurt (YouTube Video) The Efficacy of Lactobacillus Reuteri DSM 17938 in Infants and Children: a Review of the Current Evidence (Paper) The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia (Paper) The Lactobacillus casei Group: History and Health Related Applications (Paper) Towards a Better Understanding of Lactobacillus Rhamnosus GG - Host Interactions (Paper) Bifidobacterium Longum Subspecies Infantis: Champion Colonizer of the Infant Gut (Paper) Strategies to Promote Abundance of Akkermansia Muciniphila, an Emerging Probiotics in the Gut, Evidence From Dietary Intervention Studies (Paper) Genova GI Effects® Microbial Ecology Profile Test (Website) Coronary Artery Calcium (CAC) Score Testing Locations (Website) Coronary Artery Calcium Data And Reporting System: Strengths And Limitations (Paper) Understanding the NMR LipoProfile Test Report (PDF) Lipoprotein(a): Biology and Clinical Importance (Paper) Quantimetrix LIPOPRINT Test (Website) JUPITER: a Few Words of Caution (Paper) Magnesium Bicarbonate Water Recipe (Website) Molecular Hydrogen Tablets (Amazon.com) In Defense of Vitamin K2 MK-4: Dr. Price’s Activator X (Article)

In this thirteenth episode, Tom Stubbs, Co-Founder/CEO of Chronomics starts with introducing epigenetics. He describes the technology and expertise that he's brought together to create the only company in the world advancing the forefront of epigenetic biomarkers. Read the transcript He explains how their A.I. based health biomarker engine will be used to reduce your risk of future illness. Topics we discussed in this episode Focus of Chronomics Epigenetic sequencing Epigenetic ideal data type for preventive health Epigenetics ideal for figuring out age-related and chronic conditions Genomics and epigenetics provide complimentary data Histone methylation DNA methylation MTHFR gene CpG sites Chronomics health biomarker engine Epigenetics and aging Blood vs saliva as an epigenetic sampling type Arrays vs next-generation sequencing Why epigenetics is a fantastic data type Developing unique epigenetic signatures or biomarkers Polygenic risk scores Biological age and epigenetic clocks Using blood vs saliva for epigenetic clock input Arrays vs sequencing for epigenetic clock input Genetics vs epigenetics Leveraging epigenetics to personalize pharmaceutical agent or drug intervention risk/reward Leveraging epigenetics to personalize rejuvenation therapy or longevity compound reward decisions Ending flying blind as to whether things have a positive impact or a negative impact on your health Providing people with access to their molecular level biological data Ability to retain that immortality across the human existence Epigenetics in utero mechanisms Epigenetics across generations Epigenetic memory IPS reprogramming Dietary interventions on rate of biological aging Show links Chronomics (Website) Tommy Wood on Engineering Sustained Health Using A.I. & Standard Blood Chemistry (Podcast Guest #006) What is 30x and 0.4x Whole Genome Sequencing? (Article) Next-Generation Sequencing vs. Microarrays (Article) 100,000 Genomes Project (Wikipedia Entry) From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalized Medicine (Article) Homocysteine and MTHFR Mutations (Article) CpG site (Wikipedia Entry) Polygenic Score (Wikipedia Entry) Epigenetic Clock (Wikipedia Entry) Steve Horvath (Wikipedia Entry) Jeff Kaditz on Multiscale Digital Models of Human Biology, Turning Health into a Hard Science (Podcast Guest #012) The Epigenetic Landscape in the Course of Time: Conrad Hal Waddington's Methodological Impact on the Life Sciences (Paper) Induced Pluripotent Stem Cell (Wikipedia Entry) Beta Oxidation (Wikipedia Entry) Cell Potency (Wikipedia Entry) Steve Horvath (Wikipedia Entry) Dutch Famine of 1944–45 (Wikipedia Entry) Gamete (Wikipedia Entry) From Germline to Soma: Epigenetic Dynamics in the Mouse Preimplantation Embryo (Paper)

In this twelfth episode, Jeff Kaditz, Founder/CEO of Q Bio begins with coronavirus chat. He goes on to explain that most medical knowledge today is probably incorrect or heavily biased. That there’s almost nothing a doctor does that couldn’t have been done 200 years ago in terms of the information. He presents his vision to run ‘search engines for the body’ and turn healthcare into hard science.