Action plan

• APOE genotype testing: having 1 or 2 copies of e4 variant indicates higher risk for Alzheimer
• Colonoscopy: do every 2-3 years from age 40(!)
• DEXA scan: do annually; focus on visceral fat (more important than total body fat) & bone mineral density (BMD) in hip and spine
• Oral glucose tolerance test: postprandial insulin spike: eary warning sign of metabolic disorder
• Apolipoprotein B (apoB): test regularly, should be as low as possible
• LDL-C: (proxy of apoB) target: below 10-20 mg/dL
• Zone 2: 3 hours/week or four 45 min sessions
• Watts/kg: track progression in Zone 2 exercise (divide average wattage output of Zone 2 session by weight); should be 2 Watts/kg & increasing;
• VO2 max: target elite group using Table 2 in Madsanger et al (2018)
• VO2 max session: 1-2 times/week; 4 mins max pace + 4 mins easy ride; 4-6 cycles per session; e.g. rowing machine
• Farmer’s carry: walking while carrying a heavy object with your hand; goal: carry 1/4 to 1/3 of your body weight (focus on concentric/lifting up as well as eccentric/putting down); bonus: hold up kettlebell vertically; standard for males: carry 1/2 of body weight in each hand (-> full body weight in total) for 1 minute; begin with much less weight
• Rucking: hiking/fast walking with a loaded backpack (focus on concentric/going up as well as eccentric/going down)
• Pulling: pull-ups, rows
• Hip hinging movement: deadlift, squat, step-up, hip-thrusters, single-leg variants; bend at the hips - DO NOT BEND YOUR SPINE!: heavy deadlift, squat -> approach with care because of risk of injury to the spine; typically being with single-leg step-ups, split-stance Romainan deadlift with no/light weights;

• Dead-hanging: from pull-up bar for at least 2 mins for men / 1.5 mins for women

• Rapamycin: use weekly in moderate doses (off-label)
• Triglycerides: should be <150 mg/dL
• Blood pressure: should be <130/85
• HDL cholesterol: should be >40 mg in men or >50 mg in women
• Waist circumference: should be <40 inches in men or <35 in women
• Fasting glucose: should be <110 mg/dL
• Dry sauna: 4/week, 20 mins/session at 179 Fahrenheit / 82 Celsius
• Hormone replacement therapy: for women during transition from perimenopause to menopause

Part I

1. The Long Game: From Fast Death to Slow Death: Four Horsemen: heart disease, cancer, neurodegenerative disease, type 2 diabetes/metabolic disfunction; longevity = how long you live (chronological lifespan) + how well you live (healthspan)
2. Medicine 3.0: Rethinking Medicine for the Age of Chronic Disease: Medicine 2.0 (M2): based on scientific method, focus on treatment, focus on lifespan, you are a passenger on the ship; Medicine 3.0 (M3): personalized, focus on prevention, focus on healthspan, you are the captain of the ship
3. Objective, Strategy, Tactics: A Road Map for Reading This Book: objective -> strategy -> tactics; 5 domains: exercise, nutrition, sleep, emotional health, drugs; limitation of randomized controlled trials: take too long; instead: evidence-informed, risk-adjusted precision medicine

Part II

1. Centenarians: The Older You Get, the Healthier You Have Been: Jeanne Calment: died at 122, oldest person ever to have lived; “While some individuals have claimed extremely lengthy lifespans, of 140 years or more, Calment remains the only person ever to be verified as having lived past 120, leading some researchers to speculate that that may represent the upper limit of human lifespan, programmed into our genes.”; women live longer but tend to be in poorer health; potential longevity gene: APOE, CETP, APOC3 but no magic bullet; Medicine 2.0
2. Eat Less, Live Longer: The Science of Hunger and Health: radically reducing food intake lengthen life in lab mice but not recommended as a general tactic (not sustainable); rapamycin: might extend lifespan, if given in weekly moderate doses (daily doses might have unwanted side effects eg. risk of immunosuppression); no clinical trial for humans but Dog Aging Project: ongoing, ETA: 2026; both calorie restriction and rapamycin enhances recycling in the body; metformin: potential longevity benefits but no clinical trial;
3. The Crisis of Abundance: Can Our Ancient Genes Cope with Our Modern Diet?: nonalcoholic steatohepatitis (NASH) & nonalcoholic fatty liver disease (NAFJD, precursor of NASH): tip of iceberg of global epidemic of metabolic disorders ranging from insulin resistance to type 2 diabetes; first sign is rising levels of alanine aminotransferase (ALT), acceptable range adjusted to current population -> “normal” is not the same as “healthy”; metabolic health and obesity are different (one doesn’t indicate the other); “metabolic syndrome”: meets 3 or more of these criteria: 1) high blood pressure (>130/85) 2) high triglycerides (>150 mg/dL) 3) low HDL cholesterol (<40 mg in men or <50 mg in women) 4) central adiposity (waist circumference >40 inches in men or >35 in women) 5) elevated fasting glucose (>110 mg/dL); in US: 120 million have 3+, 90% have 1+, 10 million are normal weight but metabolically unhealthy; DEXA scan: visceral fat is more important than total body fat; earliest signs of metabolic syndrome: elevated uric acit, elevated homocysteine, chronic inflammation, mildly elevated ALT liver enzymes, Lipoproteins (especially triglycerides), ratio of triglicerydes to HDL cholesterol (it should be 2:1 or better yet, <1:1), levels of VLDL; canary in the coal mine: elevated insulin (postprandial insulin spike after oral glucose tolerance test is biggest early warning sign)
4. The Ticker: Confronting-and Preventing-Heart Disease, the Deadliest Killer on the Planet: cholesterol: belongs to lipid family (fats), cannot be dissolved in plasma but must be carried around by tiny particles called lipoproteins that are partly lipid (inside) and part protein (outside), protein allows them to travel in our plasma; high- and low-density lipoproteins (HDL/LDL): has to do with amount of fat relative to protein (LDL carry more lipids, HDL carry more protein in relation to fat); their traditional labels (HDL is “good” and LDL is “bad”) is misleading because it’s not the cholesterol per se that causes the problems but the nature of the particle in which it’s transported; HDL particles wrapped in apolipoprotein A (apoA), LDL in apoB; distinction is crucial: every single lipoprotein that contributes to atherosclerosis (not just LDL but several others) carries this apoB signature -> test for apoB regularly!; Lp(a) (pronounced “el-pee-little-A”): formed when LDL particle used with rarer type of protein called apolipoprotein(a) or apo(a) (not the same as apolipoprotein A which marks HDL particles); apo(a) wraps loosely around the LDL particle with ring-shaped segments (called “kringles” after the Danish pastry) which make Lp(a) very dangerous: as LDL particle passes through blood-stream, they scoop up bits of oxidized lipid molecules & carry them along; this is not necessarily bad (Lp(a) acts like a cleansing agent or a sweeping truck) but because Lp(a) is a member of the apoB particle family, it has the potential to penetrate the endothelium & get lodged in an artery wall; most important numbers on blood test: apoB and Lp(a) -> most important predictors of atherosclerotic cardiovascular disease (ASCVD); apoB tells concentration of LDL particles (which is more predictive than the cholesterol found within LDL particles, LDL-C) & also captures concentration of VLDL particles which as members of apoB family can also contribute to atherosclerosis; you want apoB as low as possible; HDL-C is not important (low HDL-C is associated with higher risk but it does not appear to be causal); LDL-C target: 10-20 mg/dL; cannot be accomplished with diet alone; statins: most prescribed drugs for lipid management, side effects: muscle-pain, usually start with rosuvastatin (Crestor), aim to bring apoB down to 20-30 mg/dL (similar to a child); other drugs (if statins don’t work): bempedoic acid (Nexletol) - no side effects but more expensive, ezetimibe (Zetia) - pairs well with statins, PCSK9 inhibitors - combine with statins, fibrates - aim to reduce triglycerides which also carried by VLDLs, ethyl eicosapentaenoic acid (Vascepa) - FDA approved to reduce LDL in patients with elevated triglycerides;
5. The Runaway Cell: New Ways to Address the Killer That Is Cancer: combining PI3K inhibitor with ketogenic diet attacks cancer on multiple fronts; immunotherapy: chimeric receptor T cells (CAR-T); “checkpoint inhibitors”; adoptive cell therapy (ACT); most important tool: early, aggressive screening; trade-off between sensitivity (ability to detect existing conditions = true positive rate) and specificity (ability to detect non-existing conditions = true negative rate); colorectal cancer (CRC); recommendation: get colonoscopy by age of forty (or sooner if higher risk); better to screen early than risk doing too late; of all Horsemen, cancer is hardest to prevent; advocate of early screening
6. Chasing Memory: Understanding Alzheimer’s Disease and Other Neurodegenerative Diseases: important first step: complicated battery of tests (cognition, memory, executive function, attention, processing speed, verbal fluency, logical/associative/spatial/semantic memory, sense of smell); “cognitive reserve”: brain’s ability to continue functioning even after some of its neural networks begin to fail (similar to “movement reserve” for Parkinson’s disease); complex tasks requiring more nimble thinking and processing are more productive at building & maintaining cognitive reserve (<-> doing crossword puzzles will only make you good at doing crossword puzzles); similarly, complex movements (e.g. dancing) more effective in building movement reserve; connection between Alzheimer’s disease and metabolic dysfunction; apolipoprotein E (APOE): e4 genotype makes every risk factor of Alzheimer’s disease worse; first step of prevention: addressing metabolic issues; single most powerful item: exercise (endurance as well as strength training), sleep is important too; surprising risk factor: hearing loss; surprising intervention: oral health (brushing AND flossing); recent addition: dry sauna (4/week, 20 mins/session at 179 F / 82 C)

Part III

1. Thinking Tactically: Building a Framework of Principles That Work for You: tactics of M3: exercise, nutrition, sleep, emotional health, drugs; car accidents: high proportion happen at intersections, usually another car hitting yours from the left on the driver side -> at busy intersections look left, then righ then left again;
2. Exercise: The Most Powerful Longevity Drug: VO2 max: single most powerful marker for longevity; can be increased by training; muscle helps us survive old age; more muscle mass delays death because it preserves healthspan; falls are by far the leading cause of accidental deaths above age 65; emphasis on weight training; Centenarian decathlon: ten most important physical tasks you will want to be able to do for the rest of your life (e.g. pick up child from floor, carry grocery bag, have sex, open jar)
3. Training 101: How to Prepare for the Centenarian Decathlon: three dimension: cardio, strength and stability; avoiding injury is equally important -> stability; Zone 2: maximum level of effort that we can maining without accumulating lactate (lactate level should be constant during Zone 2 exercise, ideally between 1.7 and 2.0 millimoles); Zone 2 heart rate ~ 70-85% of maximum heart rate; rate of perceived exertion (RPE) aka “talk test”: at the top of Zone 2 you should be able to talk but not particularly interested in holding a conversation (you’re able to talk in full sentences but just barely); very easy even for sedentary people: brisk walk, walking uphill, riding stationary bike; suggestion: 3 hours/week zone 2 or four 45-minute sessions; track progression in zone 2 by measuring your output in watts (many stationary bikes can do that): take average wattage output for a zone 2 session, divide it by your weight; expectation of fit person: 2 watts/kg, what is important is not the number but the improvement over time; you can listen to podcasts/audiobooks; 1 or 2 VO2 max workouts per week: go for 4 mins at maximum pace on rowing machine or road bike, then ride for 4 minutes easy; repeat 4-6 times and coold down; bone mineral density (BMD): measure every year (via DEXA scan) esp. in hips and lumbar spine; bone density decreases with age (similar to muscle mass); for women decline happens more quickly around menopause (-> HRT is recommended); strategies: strengh training, esp with heavy weights; strength training ~ retirement saving (goal: get enough muscle “reserve”); measure of strength: how much heavy stuff you can carry (e.g. with your hands); rucking: hiking/fast walking with loaded backpack; exercises: 1) grip strength 2) focus on both concentric (lift weight up) as well as eccentric (pull weight down) 3) pulling motion (pull-up, row) 4) hip hinging movement (deadlift/squat/step-up, hip-thrusters, single-leg variants); classic farmer’s carry: walking while carrying a heavy object with your hand; goal: carry 1/4 to 1/3 of your body weight (focus on concentric/lifting up as well as eccentric/putting down); bonus: hold up kettlebell vertically; standard for males: carry 1/2 of body weight in each hand (-> full body weight in total) for 1 minute; begin with much less weight; dead-hanging: from pull-up bar for at least 2 mins for men / 1.5 mins for women; eccentric strength: focusing on the “down” phase of lifts (pull-ups/pull-downs/deadlifts/rows/rucking downhill); pulling: rowing machine (good for VO2max training); hip-hinging: bend at the hips - DO NOT BEND YOUR SPINE!: heavy deadlift, squat -> approach with care because of risk of injury to the spine; typically being with single-leg step-ups, split-stance Romainan deadlift with no/light weights; check out videos at https://peterattiamd.com/outlive/videos/
4. The Gospel of Stability: Relearning How to Move to Prevent Injury: no 1 commandment of fitness: do thyself no harm; stability is essential; it lets us create force safely; dynamic neuromuscular stabilization (DNS): most natural movements (like babies): www.rehabps.com; Postural Restoration Institute (PRI): www.posturalrestoration.com; most basic level of stability: breath (breathing style gives insight to broader stability strategy); feet: point of contact between body and world; videos: www.peterattiamd.com/outlive/videos; spine: structure we want to protect most; slowed down cat/cow sequence; controlled articular rotations; grip: important; film yourself while working out; “Barry Get-Up”: getting up of the ground using only one (or no) arms;
5. Nutrition 3.0: You Say Potato, I Say “Nutritional Biochemistry”: Dunnig-Kruger curve: relationship between competence (Peak of “Mount Stupid” → Valley of Despair → Slope of Enlightenment → Plateau of Sustainability); avoid word “diet”, use “nutritional biochemistry” instead; high correlation between poor metabolic health & being overnourished / undermuscled; basic rules: 1) don’t eat too many calories or too few 2) consume sufficient protein & essential fats 3) obtain vitamins & minerals you need 4) avoid pathogens (eg. E. coli), and toxins (eg. mercury, lead); source of knowledge of nutrition: 1) epidemiology (problem: cannot distinguish between correlation & causation ↔ epidemiology of smoking); 2) experiments (problem: humans are terrible sorry subjects for nutrition); Brad Hill criteria for causality: (1) strength of the association (i.e., effect size), (2) consistency (i.e., reproducibility), (3) specificity (i.e., is it an observation of disease in a very specific population at a specific site, with no other likely explanation?), (4) temporality (i.e., does the cause precede the effect?), (5) dose response (i.e., does the effect get stronger with a higher dose?), (6) plausibility (i.e., does it make sense?), (7) coherence (i.e., does it agree with data from controlled experiments in animals?), (8) experiment (ie. is there experimental evidence to back up the findings?), and (9) analogy (i.e., the effect of similar factors may be considered); problem: focusing too much on small questions while ignoring bigger ones; general health is massive confounder (aka healthy user bias); myth of “moderate” drinking: there is no dose of alcohol that is “healthy”; efficacy tests (show how intervention works in perfect conditions) vs effectiveness tests (show effect in real-world conditions); PREDIMED study: clear advantage of Mediterranean diet (nuts, olive oil); problem: performance bias: subjects in treatment arms might have changed their behavior due to having more interaction with investigators; main issues with experiments: 1) compliance 2) impact of individual metabolism & other risk factors in diet;
6. Putting Nutritional Biochemistry into Practice: How to Find the Right Eating Pattern forYou: stay away from SAD (Standard American Diet) / junk food as much as you can; diets: 1) caloric restriction (best approach but you have to do it perfectly) 2) dietary restriction (common strategy but you can still overeat) 3) time restriction (intermittent fasting, latest tend but can change body decomposiz for the worse); continuous glucose monitoring (CGM): helps us understand individual carbohydrate tolerance, suggested to do it for 1-2 months to understand what foods spike your glucose; limitation of CGM: it’s only one variable; protein: typical suggested intake: 1.6 g/kg/day (for active people 2.2 g/kg/day = 1 g/lb/day); in general: the more protein we consume, the better; fats: three types: 1) saturated fatty acids (SFA) 2) boost mono-unsaturated fatty acids (MUFA) 3) polyunsaturated fatty acids (PUFA), try to boost MUFA to ~50% (→ more olive oil & avocados), reduce SFA to ~15% (→ less butter, lard, sunflower oils etc), adjust total PUFA to fill the gap (→ salmon, anchovies); fasting: 16/8 model (→ intermittent fasting) was studied in mice, no similar benefit found in humans, guaranteed to miss your protein target; fasting might be helpful for some, but not for most people; diet is important but won’t cure all ills;
7. The Awakening: How to Learn to Love Sleep, the Best Medicine for Your Brain: “if sleep is so unimportant, why hasn’t evolution gotten rid of it?”; we need to sleep ~7.5-8.5 hours a night; ~8 hour sleep cycle might be hard-wired in us; even one night of bad sleep impacts physical & cognitive performance negatively; good sleep ~ performance-enhancing drug; sleep deprived people tend to underestimate its effects of them because they adapt to it; long-term effects: “old-man blood”: elevated insulin, high triglycerides, low testosterone & older-looking, flabbier skin; poor sleep wreaks havoc on metabolism (increased insulin) probably due to stress; long sleep is also a problem (might indicate other underlying problems); poor sleep can increase hunger the next day & more likely to have extra late-night meal; strong association between poor sleep and cardiovascular disease & heart attack; good sleep might mitigate generic risk of heart disease; sleep is important for brain health especially at older age; both REM and deep sleep is important; better sleep lowers risk of Alzheimer’s; sleeping ability declines with age; deep sleep is especially important in 40s and 60s; no magic bullet for sleep (trazodone & ashwagandha might help though); first step: renounce our “addiction” to sleep deprivation; assess sleep habits (eg. HRV, questionnaires); there are different “chronotypes” (morning/evening person); rule out / address sleep apnea first; darkness is important for good sleep (use eye shade eg. Alaska Bear); swap blue-intensive LED bulbs for warmer ones; do not bring laptop/phone into bed with you; ideal temperature: 65F (use cooling mattress); cut back/give up alcohol; coffee is not a solution for poor sleep; Zone 2 exercise helps but not within 2-3 hours before going to bed; prepare mentally; avoid late night snacking; give yourself enough time to sleep: go to bed at least 8 (preferably 9) hours before you need to wake up; fix wake-up time, don’t deviate from it even on weekends; don’t obsess over you sleep (especially if you have problems); if you can’t sleep: stop fighting it, go to another room, do something relaxing/enjoyable (but never give insomnia a purpose eg. by doing work)
8. Work in Progress: The High Price of Ignoring Emotional Health: emotional & physical health closely intertwined; suicide: top 10 causes of death across all age groups; addictive opioids: mental health crisis in disguise; “why would you want to live longer if you’re so unhappy?”; author received help from Bridge (place in Kentucky): rule: no minimizing (would it be okay if someone did it to your child?), rule: not supposed to hens Kleenex when they’re crying; Trauma Tree: undesirable behaviors (addiction, codependency, propensity to anger, attachment disorders) stem from childhood trauma; trauma types: 1) abuse (physical/sexually/emotional/spiritual) 2) neglect 3) abandonment 4) enmeshment (blurring of boundaries between adults and children) 5) witness of tragic events; “big-T” trauma vs “little-t” trauma (latter more challenging to address); litmus test between trauma and adversity: would I want my child to experience it?; childhood trauma: not the event itself but the (maladaptive, dysfunctional) way the child adapts to it; mental health ≠ emotional health; I Don’t Want to Talk About It by Terrence Real: 90% of male rage is helplessness masquerading as frustration; children don’t respond to parent’s anger in a logical way; The Road to Character by David Brooks: “resume virtues” vs “eulogy virtues”; Psychological Counseling Services (PCS): Phoenix, Arizona; write out list of 47 affirmations; dialectical behavioral therapy (DBT): developed by Marsha Linehan in 1990s, backed up by evidence: emotional regulation, distress tolerance, interpersonal effectiveness, self-management; aim to create gap between stimulus and response; listening to & addressing self-talk: what would you say if your best friend had performed exactly as you?; opposite action: forcing yourself to do opposite of what I’m inclined to; exercise is also important (rucking); most important tactic: weekly therapy session; lesson from author’s story: “if I can change, you can change”; author noticed finding more joy in being than in doing; “For the first time in my life, I felt that I could be a good father. I could be a good husband. I could be a good person. After all, this is the whole point of living. And the whole point of outliving.”