#70–David Sinclair, PhD: How cellular reprogramming could slow our aging clock, & the latest on NAD

Academic institution where David Sinclair was a postdoc in Lenny Guarente's lab when sirtuin genes were discovered.

Medical institution where David Sinclair's lab's most advanced pro-drug molecule, designed to boost NAD+, is currently undergoing phase one human studies.

Academic institution where David Sinclair is a professor in the Department of Genetics.

Research institute where Juan Carlos Izpisua Belmonte showed that over-reprogramming cells can lead to tumor formation in mice.

Institution where collaborations on reprogramming experiments, particularly restoring eyesight, are taking place.

The Food and Drug Administration, whose head (Ned Sharpless) created a specific mouse model for tracking cellular senescence.

Academic institution where Josh Rabinowitz's lab conducted research on the metabolism of nicotinamide riboside.

Medical institution where Jim Kirkland researched the effects of senescent cells.

An antibiotic used in experimental reprogramming as an on/off switch for gene expression in AAV vectors, allowing controlled activation of rejuvenating genes.

A drug that inhibits mitochondria to stimulate their growth, with recent studies suggesting it may blunt exercise effects in metabolically healthy individuals, leading to a suggestion of pulsed dosing.

A drug discussed for its potential in extending lifespan in mice by around 30%, but its optimal pulsatile dosing in humans is still unclear, and it may interfere with muscle growth from exercise.

Former head of the FDA who created a mouse model where p16 gene activation caused cells/tissues to fluoresce, indicating stress or senescence.

Professor at Princeton whose lab conducted a tracer study on oral nicotinamide riboside in mice, showing initial conversion to NAD+ primarily in the liver.

Researcher based in Switzerland who has studied the effects of NR in old mice and in mitochondrial disease.

Professor in the Department of Genetics at Harvard Medical School and co-director for the biological mechanism of aging program, known for his work in understanding aging and its effects.

Scientist in whose lab David Sinclair was a postdoc at MIT when sirtuin genes were first discovered.

Scientist at the Salk Institute who demonstrated that pushing cellular reprogramming too far can induce tumors.

A colleague of David Sinclair known for his belief that future technology will allow replacement of any body part or system.

Researcher at the Mayo Clinic who conducted experiments showing senescent cells implanted into mice caused signs of premature aging.

Scientist from the 1950s who used the metaphor of an embryo rolling down a hill into valleys, representing cell differentiation and identity.

A mathematician from the 1940s who developed the information theory of communication, relevant to understanding how information is preserved and transmitted, and analogously, how epigenetic information is maintained in cells.

One of the inventors of the epigenetic clock, a mathematician at UCLA, whose work allows estimation of biological age and prediction of lifespan.

Zombie cells that stop dividing but don't die, accumulating with age and releasing inflammatory signals that stress surrounding cells, contributing to aging.

A theory proposed by David Sinclair suggesting that aging is caused by a loss of fidelity in the epigenetic information, rather than direct genetic mutations.

An epigenetic clock, invented by Steve Horvath, that measures biological age by analyzing DNA methylation patterns with high accuracy, capable of predicting lifespan and reflecting lifestyle choices.

A gene-editing technology mentioned in the context of engineering out undesirable genes in embryos, though not directly part of Sinclair's reprogramming research.

A family of genes discovered to control aging in yeast, maintaining gene silencing and responding to stress to repair DNA, requiring NAD+ for their activity.

A set of genes used in the reprogramming field to take an adult cell and convert it into a stem cell, effective for reversing cellular age.

A genetic disease often considered a poster child for gene therapy due to its single known gene mutation.

A plant molecule found in red wine, taken in high doses by David Sinclair, shown to activate sirtuin enzymes and extend the lifespan of mice on a Western diet.

A form of Vitamin B3, also known as niacin, that can raise NAD+ levels but is an effective inhibitor of sirtuins at high doses, making it less ideal than other precursors.

A molecule very similar to resveratrol, included in a high-dose NR supplement used in a small ALS patient study.

A precursor to NAD+, chemically similar to DNA and Vitamin B3, directly absorbed by cells and converted to NMN, then NAD+, making it a promising booster.

Nicotinamide adenine dinucleotide, a molecule vital for various biological processes and identified as a crucial fuel for sirtuin activity, with discussions around its replenishment and boosting effects.

A molecule that NR is converted into inside cells before becoming NAD+, also a direct precursor to NAD+ being studied for its effects.

A deep layer of the epigenome where chemical methyl groups are added to DNA to silence genes, marking a cell's identity and accumulating changes over time.

David Sinclair's book which details the information theory of aging, the nature of the aging clock, its manipulability, and ethical implications of delaying death.

A company with an FDA-approved drug that uses gene therapy to treat a type of retinal degeneration, with treatments costing hundreds of thousands of dollars.

The publisher of David Sinclair's book, whose lawyers required him to create original artwork for the book.

A type of virus used as a vector in gene therapy to deliver genes for reprogramming, bypassing the problems of older viral vectors that could integrate into the genome.