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Lewis HowesREVERSE AGING: What To Eat & When To Eat For LONGEVITY | David Sinclair
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Chapter summaries
Aging as a Disease and the Longevity Genes
Lewis Howes opens by asking whether aging is a disease. Sinclair explains that aging drives other major diseases and introduces sirtuins, the longevity genes, along with the hallmarks of aging.
- •Sinclair thinks aging is a disease and death is its end product
- •Treating cancer or heart disease one at a time is like Whac-A-Mole when aging is the main cause
- •About 50 of roughly 23-24,000 genes matter for longevity, including seven sirtuins
- •Sirtuins act like traffic cops that defend against all the hallmarks of aging
- •The longevity genes talk to each other, so tweaking one tweaks the others
Inside the Lab: Reversing Aging in Cells and Mice
Sinclair describes what his lab does, from growing and de-aging human cells and mini brains to making mice. He explains that his team is driven by questions rather than technology and that the work is meant to produce radical discoveries.
- •The lab is driven by the question of why we age and what can be done about it
- •Human skin and brain cells are grown in dishes, aged forwards and reset
- •Mini brains can be grown and aged
- •Mice can be engineered from stem cells and tested on treadmills and memory tests
- •Harvard doesn't reward obvious discoveries
Simple Habits That Turn On Longevity Genes
Sinclair says 80% of health in old age is up to you, and that a few basic habits can add about 14 years. He covers not smoking, eating less often, high intensity exercise, and the idea that mild adversity activates survival genes.
- •Twin studies suggest 80% of health in old age comes from how you live
- •No smoking, skipping meals and exercise can add about 14 years on average
- •High intensity interval training and getting out of breath trigger the longevity genes
- •The body senses adversity and switches into survival mode
- •Modern comfort works against longevity
What to Eat: Plants, Polyphenols and Olive Oil
Sinclair explains how food type affects longevity, favoring plants stressed enough to hold polyphenols, monounsaturated fats and Okinawa-style eating. He also describes eating less, stopping at 60-70% full and tricks for resisting hunger.
- •Monounsaturated fats from olive oil and avocados trigger a longevity gene
- •Stressed, colorful plants carry polyphenols such as resveratrol
- •Eating a lot of meat shuts down some longevity pathways
- •Sinclair ate an Okinawa-style diet in his 20s and 30s and now skips breakfast and lunch
- •Hot tea or water and asking what he wants to look like next year help him resist hunger
Sleep, Community and Why Sinclair Pursues Aging
Sinclair adds sleep and supportive friends to the list of basics. Asked what inspired him, he points to learning about death as a child and the loss of his mother to lung cancer.
- •Good sleep and surrounding yourself with caring friends complete the five habits
- •Treating disease late is far less effective than prevention
- •His mother was diagnosed with lung cancer at about the time he was 25 and he describes her painful death
- •His father, who looked after himself, is healthy at 80
- •His grandmother told him to make the most of life and not waste a second
College Epiphany: The Last Generation to Die Young
Sinclair describes his early life, including losing weight at university and deciding at 18 to work toward extending lifespan. He expects further gains in his lifetime and points to his father as a role model.
- •He was a chubby kid who lost 15 kilos eating carrots at university
- •At 18 he told friends they might be the last generation with a normal lifespan
- •He studied genetic engineering at the University of New South Wales
- •He thinks another 5-10 years of lifespan gain is easy
- •His father takes molecules from his lab and is healthy
Resveratrol, the Debunking and the Comeback
Sinclair tells how his lab found resveratrol activates sirtuin 1 and how a 2010 challenge to the finding devastated his career. A student's work and a new study a week before the interview support the mechanism, which mimics monounsaturated fatty acids.
- •Resveratrol from red wine lit up sirtuin 1 in tests and helped mice resist a high-fat diet
- •In 2010 companies published papers saying the effect was an artifact, and his grants and lab shrank
- •Student Basil Hubbard spent three years showing the finding was real
- •A new study suggests resveratrol mimics monounsaturated fatty acids, like olive oil without the calories
- •Mentor Lenny Guarente emailed him the paper with the subject line "Wow!"
Never Resting: Lewis's All-American Story
Sinclair says that major achievements feel like an anticlimax and he moves on to the next problem. Lewis relates this to his own decathlon All-American achievement and the feeling that nothing is ever enough.
- •Sinclair finds that milestones feel like an anticlimax
- •Lewis describes his decathlon national championships and finishing eighth
- •Lewis felt angry soon after achieving the childhood goal
- •Sinclair says restlessness is why they are both where they are
Homeless in Wales and a Rejected Paper
Sinclair shares a story he hadn't told before about spending a year without a home in Cardiff during his PhD work. He then describes a recent journal rejection of ten years of research and how it shook him.
- •At 23 he moved to Wales with little money and slept on couches met through pubs
- •Lewis shares a similar night in Philadelphia
- •Being homeless taught him he had grit
- •A 10-year project with 15 labs was rejected after one of four reviewers objected
- •He plans an appeal, and the work is available as a preprint on bioRxiv
The Epigenome: Why Cells Age
Sinclair explains his theory that cells age because they lose information, with the epigenome likened to a pianist that becomes demented. He discusses DNA breaks, sun exposure and protecting your skin.
- •Cells hold genetic information and epigenetic instructions about which genes to read
- •Aging is described as the pianist becoming demented so the wrong genes come on
- •Chromosomes break a trillion times a day, and repair disturbs the epigenome
- •Avoid smoking and sunburn, and use sun protection while still going outside
Cold, Heat and Hormesis
Lewis describes his trip with Wim Hof and asks about cold and heat therapy. Sinclair explains brown fat, hormesis and the idea that controlled adversity slows aging.
- •Sirtuin 3 responds to cold and turns on brown fat
- •Brown fat is metabolically active and releases proteins that tell the body to stay young
- •Adults can turn white fat into beige or brown fat by being cold
- •Hormesis means the body needs to be pushed to avoid complacency
- •Sinclair says combining fasting, cold, heat and exercise could add at least 15 years, maybe 25
How Much to Fast
Sinclair discusses calorie restriction in mice and what fasting regimen might work for people. He says nobody knows the exact answer, describes his own routine and explains why three-day fasts trigger autophagy.
- •Mice on calorie-restricted or time-limited diets stay active with no gray hair
- •Nobody knows the right protocol, and people differ
- •Sinclair rarely eats breakfast, tries to skip lunch, and has a normal dinner
- •Athletes might skip at least one meal
- •A three-day fast triggers deep cleansing autophagy
Adversity, Mindset and Wim Hof Experience
Lewis recounts the mountain hike in the cold and how group support and positive self-talk helped. Sinclair says experiencing adversity builds calm and perspective and that pushing yourself helps mentally even more than physically.
- •Lewis hiked a mountain in near-naked conditions with a group
- •He credits togetherness and positive self-talk for getting to the summit
- •Breathing exercises and disconnection made the week peaceful
- •Sinclair says experiencing adversity lets you appreciate calm
- •After his mother died, he judges a day by whether anyone died
Measuring Age, Lifespan Predictions and Inflammation
Sinclair discusses tracking his biological age with blood tests, trends in human lifespan and the reset switch his lab found. He then covers inflammation, aspirin, resveratrol and why he thinks he rarely gets sick.
- •A blood test once estimated his age at 58 when he was 48, and after changes a later test came out at 31
- •Children born today may live to 104 on current trends, even without breakthroughs
- •His lab has reversed aging in old mice's eyes and believes it found a reset switch
- •He hopes to be healthy into his 90s and possibly beyond 100
- •He takes 81 mg of aspirin daily, and chronic inflammation is dampened by fasting and longevity genes
Three Truths, Where to Find Sinclair and Greatness
Sinclair gives his three truths: don't settle for mediocrity, do something that scares you every day, and tell your parents you appreciate them. He shares where to find him and defines greatness as making a difference in people's lives.
- •Do something worth writing about and ignore the naysayers
- •Do something that scares you every day and take risks while young
- •Tell your parents you appreciate them, which he dedicated his book to his mother for
- •His website is lifespanbook.com and his Instagram is davidsinclairphd
- •Greatness is making a difference in people's lives, not international recognition
