2023 RAADFest Summary Day 3

Corderio launched the day with an exciting whirlwind update of changes in the political landscape, naming a couple massive investments. Followed by SENS Foundation highlighting their ability to maintain focus and organize contributions to advance the field. Kenneth Scott then pointed us at some therapies to consider after you have a stable foundation of health.

Bill Andrews gave us an argument of how and why death of individuals is a core part of evolutionary biology. This talk actually marks a major shift in perspective for the field as a whole. Beginning with Aubrey decades ago, the reductionist molecular biologists maintained focus on metabolic pathways and damage accumulation that occur within an individual and ignored the evolutionary biology that set the genetic programs. Michael Rose (a noted evolutionary biologist) followed up with a talk encouraging the use of AI to understand our biological complexity and deploying it to improve our health.

Liz Parrish won the Bacon Prize. Aubrey tells us about the important work funded by the Longevity Escape Velocity Foundation (and asks for donations).

Diane Ginsberg informs us about patient results using young plasma transfer. Nathan Bryan tells us about the importance of Nitric Oxide and nasal breathing and tells us to stop using mouthwash. Nayan Patel follows that with information about glutathione, that gives NO a longer half-life in the body.

Robert Lufkin tells us about the many benefits of rapamycin, encourages us to make some lifestyle changes, avoiding glucose spikes, and highlights ITP trials combining rapamycin with metformin + acarbose. Joseph Purita ended the day suggesting we challenge our bodies with intermittent hypoxia and a hyperoxic chaser.
People really enjoyed my costume.

Actions Items:

• don’t use mouthwash
• n-acetyl-cysteine as precursor for glutathione- donate to SENS and LEV foundations

José Luis Cordeiro

• Technological convergence: NBIC
  • Atoms -> Nano
  • Genes -> Bio
  • Neurons -> Cogno
  • Bits -> Info
• work with spain + EU parliament
• Investments in the field:
  • XPrize founder raised $101M for Longevity Vision Fund
  • HEvolution spending $1B/yr
• Immortality is possible
  • already exists as cancer- continuity of germline

SENS Foundation
Book: Ending Aging
Upcoming Conference (virtual) Sep 21-22 Ending Aging Forum

• Has been funding basic research on aging for a long time
• Focus: Rejuvenation by cleanup of accumulated damage
• Focus: Extension of *max* lifespan
• Has some spinout companies (cyclarity, ichor, oisin, repair bio)

Kenneth Scott, VivaSparkle

• amazing tech advances, Yamanaka reprogramming
• 4 interventions (to make *after* achieving a stable health foundation)
  • amniotic exosomes
  • dasatinib + quercetin (for senescent cell removal) 50mg D + 1000mg Q every 6 weeks
  • follistatin gene therapy (combat sarcopenia)
  • VSELs (very small embryonic-like stem cells)
• get involved => sign petitions, invest your time and money

Bill Andrews, Sierra Sciences

• Evolution explains the How? and Why? of population genetics
• Evo
  • not a force, but a result
  • survival of the species, not of the individual
  • depends on ability of individual to reproduce
  • accumulation mutations must be sustainable
• Aging
  • distinguish: short-lived = hasn’t raised offspring, long-lived = has
  • mutations that eliminate the short-lived are not sustainable (no reproduction)
  • all other mutations can be sustained, ex: ~1000 antagonistic plieotropic mutations
• Selection
  • population more robust when genetic pool has large variety
  • need sub-sample of individuals to survive a change in selection criteria
  • older individuals not well-adapted to newer environments
• Variability: algorithmic advancements
  • Mutation – occurs for a single cell, carried by daughter cells
  • Horizontal Transfer – two cells can mix their genes
  • Ploidy – hold more than one copy
  • Sexual Reproduction – combinations of gene variants
  • Elimination of longer-lived
    • parents = A, B, C
    • offspring = parents + AB, BC, AC
    • grandkids = parents + offspring + ABC
• end result: elimination of the longer-lived

Michael Rose

• The ideological war between Evo Bio and cellular reductionists ending
• time to reframe medicine
  • S.A.D. (standard american diet) Physician = thinks aging inevitable, immortality impossible
  • ex reductionism: Heart Disease due to a handful of molecular pathyways
  • but immortality exhibited by some species (jellyfish)- human (and many others) show late-life mortality plateau
  • Biology extremely complex
    • breeding fruit fly to 2x lifespan was 100s of mutations- we need AI to understand this complexity
  • Should put AI tools in the hands of clinicians (and patients)
    • don’t wait for the medical schools (they too slow)
    • or for continuing education programs
      

Aubrey de Grey, LEV Foundation
levf.org

• Note: First time I’ve heard George Church put a specific date on LEV
• program: Robust Mouse Rejuvenation
  • Sometimes individual drugs have no effect, but the combination synergizes
  • need to fund plenty of testing for these discoveries
  • 1000 mice, expensive interventions
    • rapamycin
    • telomerase
    • young hematopoietic stem cells
    • galacto-conjugation of Navitoclax (senolytic)
  • treatment begins with 1yr of life remaining with goal of extending an additional year and max lifespan
    

Diane Ginsberg, Young Plasma + Longevity

• Aging is a result of entropy
  
• problem: we accumulate proteins in the ECM
• our vasculature system is placed around stem cells (so they can mobilize)
• aging = inability to make proteins in quality + quantity
  • the environment they sit in matters
• need to inject young factors, removing the old factors insufficient
  • we don’t know what the important factors are
  • but young plasma has them
• showed patient results from young plasma transfer

Nathan Bryan, Pneuma Nitric Oxide Innovations
Book: Functional Nitric Oxide Nutrition

• need blood supply to all organs (esp the heart and brain)
  
  • almost every chronic condition associated with reduced supply
• NO is a vasodilator, required for hemoglobin to work
  
• loss of NO preceeds atherosclerosis by a decade
  
  • telomere attrition
  • mitochondria function + biogenesis
  • mobilization of stem cells
• need NO synthase to benefit from intermittent fasting
• preserve NO creation in the endothelium delays aging pathology
• use of mouthwash destroys bacteria that signal for NO production (don’t destroy your microbiome)
  
• NO applied to skin also improves wound healing + wrinkles

Nyan Patel, Glutathione Revolution
Book: The Glutathione Revolution

• many sources of oxidative stress, can’t avoid them all
  • high levels linked to many diseases, including auto-immune disorders
• listed 10 benefits of glutathione (powerful antioxidant)
  
  • reduced production with age, but need for it stays flat- opinion: insulin is a toxic chemical
• can increase glutathione with diet + supplements
• be sure to do a test for you levels
  • measure it inside RBC not in plasma
  • levels in sample decay very quickly
• ran a trial
  • glutathione + cyclodextrin
  • only needed 3 days, got very quick results!
  • saw inflammatory markers reduce in 1 hr
• Glutathione will increase the half-life on NO in the body
  • N-acetyl-cysteine is a precursor to glutathione, but metabolic pathway works less well with age
  • arginine is never a rate limiting resource for NO synthase

Robert Lufkin
Book: Lies I Taught in Medical School

• nutrient sensing pathway conserved from yeast to humans
  • suggest lifestyle change: avoid glucose and nutrient spikes, intermittent fast
• list of aging phenotypes improved with rapamycin
  • hair: baldness + color (rapa shampoo)
  • skin: collagen production (rapa cream)
  • periodontal disease: reversed (rapa toothpaste)
  • hearing loss: regrow cochlea hair cells
  • cardiovascular: stops stents from closing (rapa coated stent)
  • cancer: less occurrence in heart transplant patients prescribed rapa for tissue rejection
  • alzheimers: improvement in mouse model, now testing in humans
• longevity?
  • ITP result: dramatically improved survival curves
  • ITP trials show synergistic effect, 2016 combo w/metformin, 2022 combo w/acarbose
    

Joseph Purita, Intermittent Hypoxia

• when intermittent triggers hormesis
  • vs chronic hypoxia quite damaging, ex: sleep apnea
  • use a hyperoxic chaser (chamber), ex: train at high elevation recover at low elevation
• induces change in transcription
  • erythropoietin -> stimulate red blood cell production
  • vascular endothelial growth factor -> make new blood vessels
  • HIF1A expression -> preserve stem cell population, prevents differentiation
• body has 3 gaseous signals: nitric oxide (HIF1A detection), carbon monoxide, hydrogen sulfide
• 2 ways
  • local: blood flow restriction (cuff bands during exercise)
  • systemic: 9%-40% range using a mask w/calibrated air
• oxygen-hemoglobin dissociation curve