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.

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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).

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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.

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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.

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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.

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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.

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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.

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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.

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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.