Exercise, Heat, Cold & Other Stressors for Longevity

Iron and Aging

• High levels of iron can accelerate aging 
  • People with high iron levels have accelerated aging
• Iron is essential, but levels don’t need to be as high as once thought 
  • Lower levels of iron and hemoglobin seen in people who live a long time
• High iron levels can be due to genetics (hemochromatosis) or supplements 
  • Can lead to production of free radicals that damage tissues
  • Can lead to accumulation of senescent cells, which drive aging and inflammation

Free Radicals

• Three main types of free radicals: 
  • Superoxide molecule: damages proteins, leads to advanced glycation end products
  • Superoxide anion: creates most oxidative stress in the body
  • Hydrogen peroxide: can damage cells
• Iron can contribute to the production of hydroxyl radicals, which damage DNA, RNA, lipids, and proteins, driving aging and senescence

Iron Management

• Measure blood biochemistry to determine iron levels 
  • Avoid iron supplements unless necessary (e.g., women during menstruation)
  • People with hemochromatosis should be more concerned and may need to donate blood

Diet and Exercise Recommendations

• Plant-​​based diet
• Low iron levels
• Eat less often (e.g., intermittent fasting)
• Exercise to activate protective mechanisms (mTOR, AMPK, Sirtuins)

Adversity Mimetics and Survival Circuit

• Adversity mimetics: actions that create or mimic biological adversity for better lifespans and health spans
• Survival circuit: genes that control aging, activated by adversity 
  • Discovered by Cynthia Kenyan in the 1990s with her work on C. elegans
  • Found that a single gene mutation could double the lifespan of the worms
    Longevity Genes and Adversity
• Longevity genes discovered in the 1990s 
  • Cynthia Kenyon found the first longevity gene in worms (Daft two)
  • Lenny Guarente found similar genes in yeast
• Longevity genes respond to adversity 
  • Single gene alteration can have a huge impact on an organism’s lifespan
  • These genes work on a circuit that starts with adversity
  • Stress resistance is activated, making organisms more resilient
• Three main pathways that control longevity genes 
  • mTOR: senses levels of amino acids in the cell
  • AMPK: senses energy and glucose
  • Sirtuans: sense NAD, a molecule that increases with exercise and hunger

Tricking the Body into Adversity

• Modern society is built on comfort, which is detrimental to long-​​term health 
  • Our bodies have evolved to fight back against adversity
  • Comfort leads to lethargic longevity defenses
• Ways to trick the body into adversity 
  • Eating less often (intermittent fasting with adequate nutrition)
  • Exercise: getting off your butt and moving 
    • Exercise can slow down cancer, cardiovascular disease, and all-​​cause mortality
    • 10,000 steps a day goal is popular, but even 4,000 steps can have health benefits
    • Walking after a meal helps maintain glucose levels

Exercise and Aging

• Exercise is not just beneficial for fitness and vitality, but also for preventing diseases 
  • Can slow down the ticking of the biological clock (Horvath clock)
  • Any kind of exercise is good, from walking to more intense activities
  • Aim for at least 4,000 steps a day, with 10,000 steps being an even better goal
    Exercise and Longevity
• Exercise stimulates the uptake of glucose and production of new blood vessels
• Low-​​level exercise activates AMPK, which registers energy in the cell 
  • High levels of AMPK activity lead to more mitochondria and long-​​lasting benefits
• Vigorous exercise increases breathing and heart rate, causing hypoxia (low oxygen levels) 
  • Hypoxia activates HIF‑1 alpha, which controls new blood vessel growth and mitochondria
  • Free radicals are generated, stimulating mitohormesis and providing various benefits
• Exercise increases glucose sensitivity, preventing type 2 diabetes and cardiovascular disease 
  • VEGF protein is produced during exercise, promoting new blood vessel formation
  • Aging can cause defects in this signaling pathway, but restoring NAD production can help
• Exercise impacts the epigenome, regulating DNA and affecting the aging process 
  • People who exercise regularly have a younger epigenetic age according to the Horvath clock
    Exercise and Aging
• Exercise slows down overall rate of aging
• Proteomic clock: measures proteins in the blood that change predictably over time 
  • GDF 15: biomarker for aging
  • Mediterranean diet slows aging process, affects GDF 15 methylation
• Epigenetic clocks, proteomic clocks, and immuno clocks can be used to understand what slows down aging and how to reverse it
• Exercise can make people biologically younger according to proteomic and epigenetic clocks

Types of Exercise

• Best exercise is the one you enjoy and will do consistently
• World Health Organization and Mayo Clinic recommend at least 75 minutes of vigorous exercise per week 
  • Better if spread out over the week
• Resting heart rate is a good measure of fitness 
  • Lower resting heart rate indicates better fitness

Measuring and Monitoring Health

• Wearable devices and biomonitors can track various health parameters 
  • Can help predict heart attacks, flu, depression, etc.
• Inside Tracker: blood test that measures biomarkers and calculates “inner age” 
  • Helps optimize health and track progress over time
• In the future, people will be monitored more frequently and accurately, leading to better health outcomes and more personalized care
  Exercise and Longevity
• Low-​​intensity exercise: walking, standing desk, treadmill desk 
  • Aim for at least 4,000 steps daily
• High-​​intensity exercise: high-​​intensity interval training (HIIT), running on a treadmill 
  • 10–15 minutes per day, 75 minutes per week
• Muscle building: weightlifting, push-​​ups, sit-ups 
  • Maintain muscle mass for hormone balance and overall health

Hyperbaric Oxygen Treatment (HBOT)

• Hyperbaric chambers increase pressure and oxygen intake
• Known to help with wound healing and neurological disorders
• Recent studies show potential for reversing telomere shortening and slowing down aging
• More research needed, but promising results in memory improvement, telomere lengthening, and cognitive performance

Other Adversity Memetics

• Cold temperatures
• Heat exposure
  Hyperbaric Oxygen Treatment
• Easy intervention, easy to test people
• Israeli study: 30 people, 60 daily sessions of 90 minutes, 5 per week 
  • Results: Reversed aspects of aging, impacts on senescent cells
• Hyperbaric centers run by doctors in major cities, growing rapidly
• Future possibility: Mimic exercise by lying down and experiencing high levels of oxygen for a short period

Cold Therapy

• Production of brown fat 
  • Brown fat: Found in babies, adults have some on their back and shoulder blades
  • Revs up metabolism, burns white fat, secretes proteins that make the body healthy
• Cold impacts all organisms, benefits seen in worms and mice
• Uncoupling proteins in mitochondria generate heat and reduce free radical load
• Cryotherapy: Short term, acute, super intense cold exposure 
  • Stimulates mitochondria, builds brown fat
  • Best to start midlife or earlier, as old mice don’t make brown fat as well as young mice
• Alternative cold therapies: Cold showers, sleeping with fewer covers

Heat Therapy

• Taking the body out of its comfort zone
• Sauna bathing: Ancient therapy for longevity, enjoyable, good for skin
  Sauna Bathing and Health Benefits
• Sauna bathing has a long history, dating back to Roman times and continuing in Scandinavian countries
• Studies show men who partake in sauna bathing a few times a week have up to a 20% reduction in cardiovascular disease and mortality caused by heart attacks
• Sauna bathing activates heat shock proteins (HSPs) which help fold proteins correctly and stimulate beneficial pathways, such as building new blood vessels and making more mitochondria
• Turning up heat shock proteins in model organisms (e.g., worms) also leads to longer lifespans

Types of Saunas

• Traditional saunas: cedar planks and hot rocks
• Infrared saunas: infrared light penetrates the skin and may reverse aspects of aging, including improving hair growth

Benefits of Exercise, Cold, Heat, and Hyperbaric Treatments

• All these treatments activate endorphins and defense pathways at the cellular level
• A basic protocol could include exercise, cycling heat and cold treatments, and hyperbaric treatments (though access to hyperbaric chambers may be limited and expensive)