Quantified Health, Wellness & Aging

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 [https://blog.hyperwellbeing.com/021-nichola-conlon-nr-vs-nmn-vs-nuchido] 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 [https://nuchido.com/] (Company Website) * ChromaDex [https://www.chromadex.com/] (Company Website) * Elysium Health [https://www.elysiumhealth.com/] (Company Website) * Elysium Health, Inc. Loses Appeal of Patent Challenge Decision [https://www.bloomberg.com/press-releases/2020-04-14/elysium-health-inc-loses-appeal-of-patent-challenge-decision-upholding-validity-of-chromadex-intellectual-property] (Press Release) * Orthomolecular Medicine [https://en.wikipedia.org/wiki/Orthomolecular_medicine] (Wikipedia Entry) * Abram Hoffer [https://en.wikipedia.org/wiki/Abram_Hoffer] (Wikipedia Entry) * Niacin: The Real Story: Learn about the Wonderful Healing Properties of Niacin [https://amzn.to/35q3TY2] (Amazon, Book) * Orthomolecular Medicine for Everyone [https://amzn.to/3lvfACm] (Amazon, Book) * GlycanAge [https://glycanage.com/] (Company Website)

In this twentieth episode, Polina Mamoshina introduces recently launched Deep Longevity, and its app (young.ai). Read the transcript [https://blog.hyperwellbeing.com/020-polina-mamoshina-deep-biomarkers-of-aging-and-longevity] 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 [https://deeplongevity.com/] (Company Website) * Insilico Medicine [https://insilico.com/] (Company Website) * Human Longevity, Inc. [https://www.humanlongevity.com/] (Company Website) * Regent Pacific Group [http://www.regentpac.com/] (Company Website) * Young.AI [https://young.ai/] (App from Deep Longevity) * Aging.AI [http://aging.ai/] (Biological Age Prediction) * ‘DNA Methylation Age of Human Tissues and Cell Types’ [https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-10-r115] (Paper) * ‘Assessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research’ [https://academic.oup.com/biomedgerontology/article/75/3/463/5717592] (Paper) * Steve Horvath [https://en.wikipedia.org/wiki/Steve_Horvath] (WikiPedia Entry) * ‘Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates’ [https://www.cell.com/molecular-cell/fulltext/S1097-2765(12)00893-3] (Paper) * Gregory Hannum [https://www.linkedin.com/in/gregory-hannum-87848421/] (LinkedIn) * Morgan Levine [https://www.linkedin.com/in/morgan-levine-aa957463/] (LinkedIn) * ‘An epigenetic biomarker of aging for lifespan and healthspan’ [https://www.aging-us.com/article/101414] (Paper) * Elysium Health [https://www.elysiumhealth.com/] (Company Website) * ‘DNA Methylation GrimAge Strongly Predicts Lifespan and Healthspan’ [https://pubmed.ncbi.nlm.nih.gov/30669119/] (Paper) * FOXO BioScience [https://foxobioscience.com/] (Company Website) * NHANES III [https://wwwn.cdc.gov/nchs/nhanes/Nhanes3/Default.aspx] (CDC) * AgeoTypes [https://med.stanford.edu/news/all-news/2020/01/_ageotypes_-provide-window-into-how-individuals-age--stanford-st.html] (Stanford Article) * GlycanAge [https://glycanage.com/] (Company Website) * GENOS [https://genos-glyco.com/] (Company Website) * ‘Biohorology and Biomarkers of Aging: Current State-of-the-Art, Challenges and Opportunities’ [https://www.sciencedirect.com/science/article/pii/S1568163719302582] (Paper) * ‘Deep Aging Clocks: The Emergence of AI-Based Biomarkers of Aging and Longevity’ [https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(19)30114-2] (Paper) * ‘Deep Integrated Biomarkers of Aging’ [https://link.springer.com/chapter/10.1007/978-3-030-24970-0_18] (Paper) * ‘Deep Biomarkers of Aging and Longevity: from Research to Applications’ [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914424/] (Paper)

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 [https://blog.hyperwellbeing.com/019-stephen-matlin-telomere-length-hallmarks-of-aging] 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 [https://lifelength.com/] (Company Website) * T.A. Sciences TA-65 [https://www.ta65uk.co.uk/] (UK/Europe) * T.A. Sciences TA-65 [https://amzn.to/2FIRrIR] (Amazon.com) * Hayflick, His Limit, and Cellular Ageing [https://www.nature.com/articles/35036093] (Paper) * The Hayflick Limit [https://embryo.asu.edu/pages/hayflick-limit#:~:text=The%20Hayflick%20Limit%20is%20a,programmed%20cell%20death%20or%20apoptosis.] (Embryo Project Encyclopedia) * The End-Replication Problem [https://www.nature.com/articles/39210] (Paper) * Leucocyte Telomere Length And Risk Of Cardiovascular Disease: Systematic Review And Meta-analysis [https://www.bmj.com/content/349/bmj.g4227] (Paper) * Association Between Leucocyte Telomere Length And Cardiovascular Disease In A Large General Population In The United States [https://www.nature.com/articles/s41598-019-57050-1] (Paper) * The Hallmarks of Aging [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/] (Paper) * Coefficient of Variation [https://en.wikipedia.org/wiki/Coefficient_of_variation] (Wikipedia Entry) * A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5178008/] (Paper) * The Telomerase Activator Ta-65 Elongates Short Telomeres And Increases Health Span Of Adult/old Mice Without Increasing Cancer Incidence [https://pubmed.ncbi.nlm.nih.gov/21426483/] (Paper) * Discovery Of Potent Telomerase Activators: Unfolding New Therapeutic And Anti-aging Perspectives [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755196/] (Paper) * The Nobel Prize in Physiology or Medicine 2009 [https://www.nobelprize.org/prizes/medicine/2009/illustrated-information/] (Website) * Defy Time [https://defytime.com/] (Website) * Telomere Benefits™ [https://www.davincilabs.com/telomere-benefits-153-60.html] (Product Link) * Mathematical Connection Between Short Telomere Induced Senescence Calculation And Mortality Rate Data [https://www.biorxiv.org/content/10.1101/2020.06.15.152348v1] (Paper) * Comparison Of Telomere Length Measurement Methods [https://royalsocietypublishing.org/doi/10.1098/rstb.2016.0451] (Paper) * Beyond Average: Potential For Measurement Of Short Telomeres [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409675/] (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 [https://blog.hyperwellbeing.com/18-alexis-shields-blood-testing] 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 [https://dralexisshields.com/] (Website) * Stop Flushing Terabytes of Data Down the Toilet [https://podcast.hyperwellbeing.com/episode/011-daniel-maggs-stop-flushing-terabytes-of-data-down-the-toilet/] – (EP11: Daniel Maggs, bisu) * Nordic Labs [http://nordiclabs.com/] (Website) * TG:HDL – Heart Disease Risk Calculator [https://www.thebloodcode.com/calculators/] (Online Tool) * KSM-66 Ashwagandha Extract [https://ksm66ashwagandhaa.com/] (Website) * Rhodiola Rosea [http://rhodiolarosea.org/] (Website) * Hormesis [https://en.wikipedia.org/wiki/Hormesis] (Wikipedia Entry) * Lymphocytes Definition [https://www.bbc.co.uk/bitesize/guides/ztp9q6f/revision/4] (Article) * Leukocytes Definition [https://www.britannica.com/science/white-blood-cell] (Article) * Neutrophils Definition [https://www.immunology.org/public-information/bitesized-immunology/cells/neutrophils] (Article) * BloodSmart.ai [https://bloodsmart.ai/] (Website) * C-Reactive Protein [https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/82047] (Article) * LIPOPRINT LDL Subfractions Test [https://quantimetrix.com/lipoprint/] (Website) * NMR Lipid Profile [https://drjockers.com/nmr-heart-disease-risk/] (Article) * DUTCH Test [https://dutchtest.com/] (Website) * Anion Gap [https://en.wikipedia.org/wiki/Anion_gap] (Wikipedia Entry) * HOMA-IR Calculator [https://www.thebloodcode.com/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 [https://blog.hyperwellbeing.com/017-gordan-lauc-017-gordan-lauc-measure-glycans-to-know-how-much-healthy-life-youve-already-consumed/] 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 [https://glycanage.com/] (Website) * Genos [https://genos-glyco.com/] (Website)