Dr. David Sinclair on Armchair Expert with Dax Shepard


Dr. David Sinclair (@davidsinclair) is a professor of genetics at Harvard, author, and expert on aging and longevity.

Lifespan: Why We Age and Why We Don’t Have To by David Sinclair

Host: Dax Shepard (@daxshepard

Key Takeaways

  • “Your DNA is not your destiny.” – David Sinclair
  • Prevention is the best way to approach medicine and makes social sense – we don’t want people to be sick
  • Theoretically, we can change our DNA such that will make it virtually impervious to any virus
  • Embryonic genes act as a reset button, allowing us to turn back the clock on genes that have not aged properly
  •  “I’m more optimistic than I’ve ever been” – David Sinclair  
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Why Does Aging Happen?

  • In a general sense, we age because of entropy: things fall apart unless we rebuild them
  • Evolution builds what’s necessary, and that’s it  
  • If there was evolutionary pressure on our species to live 300 years, we probably would have evolved to do so
  • The force of natural selection that keeps you alive declines with aging
  • There’s a tradeoff between longevity and reproduction
  • Energetically, if you’re putting your efforts into living longer you’re going to breed slower
  • We used to die in our 40s from infection, war, or starvation so our bodies are not adapted to live much beyond that
  • “It’s biologically possible to live many thousands of years. It’s not against the law of biology or even physics because we’re consuming energy and using it to rebuild.” – Dr. David Sinclair
  • Aging comes from an error in the copying process and the ability to maintain the integrity of cells over time

Stigma in Aging and Longevity Research

  • Traditional thinking is that aging is a natural process so we should wait until a disease of aging presents then apply traditional medicine
  • Longevity researchers are trying to prevent adverse effects of aging before they happen by understanding the causes of diseases of aging
  • Often, longevity research is misunderstood as a gimmick to look young forever
  • If we can make an 80-year old as resilient as a 10-year old, we can avoid diseases that arise later in life such as heart attack and Alzheimer’s  
  • Prevention is the best way to approach medicine and makes social sense – we don’t want people to be sick

DNA, The Epigenome, And Aging

  • Every cell has a different program so the DNA is in different patterns of loops and bundles
  • Without the epigenome, we’d be a giant ball of egg cells instead of becoming an organism
  • An emerging theory is that aging is more than just a DNA issue  
  • It appears we lose epigenome so DNA is not being read efficiently
  • DNA is the recipe and the epigenome decides what will be read from the recipe list – over time, the recipe becomes misread

Impactful Breakthroughs in Aging and Longevity

  • Longevity technology ranges from taking pills and all the way to human clinical trials
  • We now know that time in womb impacts life for decades to come
  • Only about 20-25% of lifespan is determined by parents’ DNA, the rest is epigenetic – this means that lifestyle has a huge impact on how we age
  • “DNA is not your destiny” – David Sinclair
  • The age of the sperm has an impact on how long you live, more than the age of the mother’s egg
  • In animal models, we can reverse the age of ovaries in mice and horses so the animal can become fertile again

Steve Horvath (UCLA): Discovered Methyl Accumulates on DNA as We Get Older

  • If we could plot where methylation was happening, we could predict the biological age of a person
  • From there, we can go back to earlier state of cell by erasing epigenome replacing with younger cells
  • Still more to learn because you can erase too far back and get hyper organ growth and cancer

Shinya Yamanaka (Japan): Discovered a Revolutionary Method to Generate Stem Cells from Existing Cells in the Body

  • There are four pivotal genes early in life that can be injected into adult cells to erase their adulthood and get them back to a stem cell you can turn into anything
  • The same genes can drive aging backward but you can’t take all four genes or you will have worse uncontrolled outcomes, like cancer
  • New research is taking three out of four genes and testing outcomes
  • Using the Yamanaka genes, we can turn back the age of an eye back by taking virus-carrying embryo genes and injecting into diseased eye

Future Research and Timelines

  • With regard to epigenome reversing, we think in the cell there’s a backup copy of youthfulness cells but we don’t know where
  • We’re looking for two types of information: what we wan to change and by how much
  • By engineering cells to block receptors, we change our DNA such that will make it impervious to any virus
  • We need a treatment where every nerve cell in the body remembers how to be a nerve cell and wakes up
  • Within 2 years, we will hopefully have results reprogramming the eye and begin expanding research on other organs  
  • Within 20 years, hoping to reprogram the body

Ethical Considerations of Increasing Lifespan

  • If we live longer, will life have the same value?
  • Knowing we could live for hundreds of years, will we think twice before engaging in risky activities we might currently do because death is inevitable?
  • Will we reinvent ourselves repeatedly if we have time?
  • Is gratitude rooted in inevitable death?
  • If you reverse aging in the brain, do you lose your memory? Do you regain lost memories?
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Notes By Maryann

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