July 18, 2020

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.

Host: Dax Shepard (@daxshepard)

“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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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

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

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

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

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

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?

aging, DNA, epigenome, longevity
Notes By Maryann