Lessons from: Outlive

Name: Outlive
Author(s): Attia, Peter ; Gifford, Bill

Synopsis

A book that I wanted Peter to write for a long time. See, I've been a listener to Peter's podcast, The Drive, for a few years now and even before that, almost since I started college back in 2008, I've been deeply fascinated, interested and invested in the field of health and longevity. Even if the vagaries of life placed me in business school - I think that there is a little doctor in me somewhere and maybe one day I will get a chance to combine my business education with my interest in longevity. Anyway, every time I used to listen to a podcast episode from Peter I used to think to myself "Wow, there is so much valuable information here, but it's all verbal and spans multiple episodes, I wish there was a book I could read". Well it might be that people like myself would have given him this feedback and the result, Outlive, could not have come at a better time. The next dozen or so books that I will read are going to be on health (#healthy). The book is a relatively long one, not too long and a little technical for the average reader - a serious book about health for people serious about their health.

Two basic premises of the book are that modern medicine:

1. Has become good at fixing "fast death" i.e., death from stuff like accidents - But when it comes to "slow death" i.e., death from heart disease, diabetes, cancer and neurodegenerative disease, it has a lesser idea on how to fix the problem.
2. Focuses on cure instead of prevention i.e. starts acting when a patient goes above a threshold of "seriousness", like a fasting glucose of 160 mg/dl - While not focusing on the root cause of the problem that may have started taking hold 10, even 20 years before.

And with these premises in place the book attempts to educate the reader on how they may view their own lifespan and healthspan on the proper timescale. It's a hopeful book that tells us that our longevity is more malleable and more in our control than we think. But the time to act is NOW.

Core ideas

1. The Four Horsemen of modern-day death are: heart disease, diabetes, cancer and neurodegenerative disease. All of us are likely to be affected by these in the modern day and age we live in (unless we try to do something about it). Centenarian live so long not because these diseases never afflict them but that they are able to forestall the advent of these diseases in their bodies 10, 20 even 30 years later than when an average person is expected to get them. They have a very short "marginal decade", i.e., the last 10 years or so of our lives where it gets progressively worse and we have difficulty performing activities of daily living, not a fate that any of us would want. This, BTW links to healthspan which is this book's primary goal - What changes can we make in our lives so that we continue functioning, living and thriving into our sunset years. The goal is to "square the longevity curve" where our health remains good (even great) for most of our lives and the period of decline is short and death, when it has to, comes quick. No burden on anyone eh?
2. Medicine 3.0: Is the stage when the practice of medicine changes from being reactive to being proactive (prevention vs cure), is focused more on healthspan than just lifespan, does not consider each individual patient homogenous (so is less dogmatic about convention and also works towards personalized/precision medicine, though the author points out that we are not really there yet) - And so is able to stop the Four Horsemen in their tracks long before patients present symptoms. It also takes a much longer view of life, like 30-40 years into the future, unlike today where Medicine 2.0 gets serious when a patient is looking at single digit "years to live" diagnoses. And finally, "In Medicine 2.0, you are a passenger on the ship, being carried along somewhat passively. Medicine 3.0 demands much more from you, the patient: You must be well informed, medically literate to a reasonable degree, clear-eyed about your goals, and cognizant of the true nature of risk.".
3. The dance of hunger and health: Generally, if you eat less, your body gets fitter. The body activates autophagy, produces newer mitochondria . There is a goldilocks zone to this, as you do not want to starve yourself to the point of harm - maybe like 80% to satiety as the Okinawans are popularized to do. Due to the consistency of results from studies, intermittent fasting (IF) and other fasting protocols have gained popularity. Limiting the amount of resources available to cells triggers pathways that make it more resilient and are linked to mTOR (short for "mechanistic target of rapamycin"). mTOR is the protein complex that tells a cell when to grow and when to conserve energy. Recently it has been discovered that the molecule rapamycin turns down mTOR and in doing so is able to signal to the body to "clean house and optimize with what you have". Rapamycin also deals with senescent cells by reducing the inflammatory cytokines that these cells release.
4. Understanding metabolic syndrome
1. Our modern society has an abundance of resources that our genes were never evolutionarily "programmed" to handle. When it comes to calories; we, in the developed world, are consuming far more than we are expending.
2. Calories enter our muscle cells and liver as glycogen for near term use. Our bodies can handle a little more calories than what are immediately needed by storing them as subcutaneous fat, but when those fat stores (that differ from person to person) fill up, the body has to find other places to store the excess fat - muscles, pancreas, liver, kidneys, heart and around organs (visceral fat) - these places are not meant to store this excess fat and lead to many problems.
3. Over time the body develops insulin resistance - this is called metabolic syndrome and is characterised by the following 5 features (meeting 3 or more means the person has metabolic syndrome):
1. High blood pressure (BP) - >130/85
2. Low HDL cholesterol - <40 mg/dL for men, <50 mg/dL for women
3. High central adiposity - Waist circumference >40 cm
4. High triglycerides - >150 mg/dL
5. Elevated fasting glucose - 110 mg/dL
4. Metabolic syndrome manifests as type 2 diabetes which can be thought of as a "gateway disease" since people with it are more susceptible to cardiovascular diseases, cancer and nondegenerative diseases. Therefore, the first step for a long and healthy life stats with getting your metabolic house in order.
5. Being metabolically unhealthy does not necessarily mean being fat - metabolic dysfunction, not obesity, drives the negative health outcomes.
6. The following tests are useful in ascertaining metabolic health:
1. Hba1C
2. Ratio of Triglycerides to HDL: Should be lower than 2:1 and closer to 1:1. Also check VLDL levels.
3. Oral glucose tolerance test (OGTT): Also, in addition to measuring glucose, start measuring insulin in your blood as well, if it is continually elevated it may be a precursor of bad things to come.
4. DEXA scans reveal the amount of visceral fat you are carrying, getting one once a year is useful. Understanding cardiovascular health.
5. Uric acid tests are potential early indicators, as higher uric acid may indicate risk.
5. Understanding cardiovascular health
1. Heart disease and stroke, collectively called atherosclerotic cardiovascular disease (ASCVD) is the #1 disease globally by the number of people it kills each year.
2. Cholesterol is not the problem (it is essential to life), the problem is the stuff that the cholesterol (a lipid) is carried in (a protein) in the bloodstream.
3. These lipid + protein structures, called lipoproteins, can have different ratios between the lipid part and the protein part - if the ratio of fat to protein is high then they are called low density lipoproteins (LDL), and if its low then they are called high density lipoproteins (HDL).
1. HDLs are often called the "good fat" but the fat has nothing to do with it - both the fat in HDLs and LDLs is the same. Instead, the nature of the particle is the issue - each lipoprotein is wrapped by a larger molecule called an apolipoprotein. HDLs are wrapped in apolipoprotein A (apoA), LDLs are wrapped in apolipoprotein B (apoB).
2. The more (number of) apoB particles one has in their bloodstream, the higher the risk. Because apoB particles have a tendency to stick to the wall of the blood vessel, then oxidize, that leads to foam cell build up, that then converts into a plaque that finally becomes calcified (and is revealed in a calcium scan). These calcified plaques obstruct blood flow through the vessel.
3. And then this happens: "Normally, however, most atherosclerotic plaques are fairly undramatic. They grow silently and invisibly, gradually occluding the blood vessel until one day the obstruction, due to the plaque itself or a plaque-induced clot, becomes a problem. For example, a sedentary person may not notice that she has a partially blocked coronary artery until she goes outside to shovel snow. The sudden demands on her circulatory system can trigger ischemia (decreased blood delivery of oxygen) or infarction (tissue death from no blood flow)—or, in layman’s terms, a heart attack or a stroke. It may seem sudden, but the danger was lurking all along."
4. You should try and get your LDL and apoB levels as low as possible:
1. Your body needs 20mg/dL of it, anything more is not needed. The author notes: "Because the total amount of cholesterol contained in all our lipoproteins—not just LDL, but also HDL and VLDL—represents only about 10 to 15 percent of our body’s total pool of cholesterol. So the concern is unwarranted, as demonstrated by scores of studies showing no ill effects from extremely low LDL concentrations."
2. Getting LDL to such a low level is a two-step process, the first step is something all of us should do. The second step, well, to each their own.
1. First step: nutritional and lifestyle interventions.
1. Quit smoking
2. Manage your blood pressure (whole another topic, I know)
3. Ketogenic diet, or if that is too hard to follow, at least reduce or limit intake of saturated fat ("half of people who consume high amounts of saturated fats … will experience a dramatic increase in apoB particles, which we obviously don’t want."). Monounsaturated fats should constitute 60% of overall fat intake.
2. Second step: Drugs, statins and others, that lower one's lipids and get them into more manageable limits (in the book, however, the author's goal is to get LDL to 20-30mg/dL, which is far more aggressive). The author lists several of them that one can use solo or in combination.
5. Following tests are useful to check cardiovascular health:
1. The usual lipid tests: But make sure you also get a apoB test done.
2. Calcium score: Predictor of future risk and also a measure of existing damage.
3. CT angiogram: A more advanced kind of CT scan that may reveal early stage cardiovascular damage that may not be revealed by a calcium test.
4. C-reactive protein (CRP)
6. The good news is that both metabolic syndrome and ASCVD are preventable and manageable through lifestyle changes and drugs (or both if necessary). Can't say the same about cancer or neurodegenerative disease though.
7. What you can do about cancer
1. The problem with cancer is that detecting it is hard, and by the time it is detected, it is too late. Therefore, try not to get it, and if you do get it, detect early and treat aggressively.
2. Cancer is not one disease, it is a complicated condition. Therefore, it has no one cure.
3. Cancer can metastasize, i.e. travel from one part of the body to another, this is bad and often when you hear "someone dying from breast or prostate cancer, or even pancreatic or colon cancer, they died because the cancer spread to other, more critical organs such as the brain, the lungs, the liver, and bones.".
4. Killing cancer cells is easy, but our current treatments also kill a lot of healthy cells along the way.
5. Cancer cells consume vastly more amounts of glucose, but instead of using that glucose to produce energy they produce building blocks for their own proliferation.
6. Cancer and metabolic syndrome are linked. Being metabolically unfit makes you more likely to get cancer.
7. "Fasting, or a fasting-like diet, increases the ability of normal cells to resist chemotherapy, while rendering cancer cells more vulnerable to the treatment.". But note that this is not a cure, just a way to stack the odds ever so slightly in your favour.
8. Cancer cells are also able to hide from the immune system. But immunotherapy, i.e. getting your own immune system to recognize cancerous cells and kill them, is gaining popularity. There are drugs today that can help make cancer visible to specific cells like T-cells or the entire immune system. However, all in all immunotherapy can only treat about a third of cancers and does not work each time (but when it works it really works), and so only 8% of cancer deaths can be prevented from it. But is it promising and let us see where the future takes us.
9. Therefore, as of today, early detection is our best bet against cancer. But here too, we are not terribly great at detecting cancer, and there is a genuine risk of false positives. To counter that we should stack different tests and see if they are all in alignment.
8. Understanding neurodegenerative diseases
1. Like cancer, here too we do not know much and can't do much if one already has advanced forms of Alzheimer's or Parkinson's, thus prevention is the best bet.
2. APOE gene testing reveals what's your apolipoprotein genotype and if you have one or (worse) two copies of the e4 allele then you are at very high risk of neurodegenerative diseases (yes, plural). BTW if you have the e2 allele then your risk if lower. Most people have the e3 allele. However, these are just direction and with the right preventive initiatives one can reduce their chances of catching any disease.
3. Alzheimer’s disease is almost twice as common in women than in men. This is partly explained by the fact that women live longer than men, but that's not the entire explanation. The opposite is true for Parkinson's and Lewy body dementia, which is twice as common in men.
4. Like the other diseases, neurodegenerative diseases often start so slow that they may be missed altogether until it is too late. Early stages are often called "mild cognitive impairment" (MCI). Impairment is diagnosed with a series of tests that check for executive function, attention, processing speed, verbal fluency and memory (recalling a list of words), logical memory (recalling a phrase in the middle of a paragraph), associative memory (linking a name to a face), spatial memory (location of items in a room), and semantic memory (how many animals you can name in a minute, for example).
5. Just like the rest of the body, the brain is a compensating machine i.e. it has the ability to compensate for weakness in one area through upregulating other areas. Just like we can "cheat" a bicep curl by swinging the abdomen forward at the start of the concentric motion, the brain too can "cheat" its way into solving a problem through a different process if the original process is compromised. This is not a bad thing actually, this means that those of us who develop a multi-faceted skillset such as playing different instruments, reading widely, having diverse social connection (that hopefully give us sense of purpose), solving variety of mental puzzles/exercises, performing various exercises (esp. those related to stability/calisthenics) will be able to tackle the inevitable decline much better. This is called cognitive reserve (for Alzheimer's) and movement reserve (for Parkinson's).
6. Robust blood flow and presence of glucose is critical to maintaining brain health, which also may indicate why someone with symptoms of vascular disease (i.e. calcification) or malfunctioning glucose metabolism in the brain are often candidates for neurodegenerative diseases.
7. Prevention of neurodegenerative diseases:
1. The single most powerful item is exercise, which has a two-pronged impact on Alzheimer’s disease risk: it helps maintain glucose homeostasis, and it improves the health of our vasculature. Esp. zone 2 endurance training and strength training.
2. Getting good sleep, and eliminating factors that cause disruptions in one's sleep cycle.
3. Ketogenic diet may offer a real functional advantage: when someone is in ketosis, their brain relies on a mix of ketones and glucose for fuel. Studies in Alzheimer’s patients find that while their brains become less able to utilize glucose, their ability to metabolize ketones does not decline.
4. Regularly brushing and flossing: One microbe in particular, called P. gingivalis that commonly causes gum disease, is responsible for large increases in levels of inflammatory markers such as IL-6.
9. While our genome is immutable (genetics), gene expression (epigenetics) can be influenced by environment and behaviour.
10. Centenarian decathlon: Imagine the target age you would like to live to (say, 85, 90, 95 or 100 years), now imagine the things you would like to do at that age such as playing sport, playing an instrument, playing with grandkids, traveling, teaching/mentoring, cooking, dancing and so on. To fully enjoy these activities and perform them well you will need a body and mind that supports. The centenarian decathlon is a concept that requires us to backcast from that time period to the present day and make a plan of what activities we need to perform today to have a body and mind that will make that vision a reality. The author invites all of us to make such a plan for ourselves and design our health and fitness regimen accordingly.
11. If you improve healthspan, you will improve lifespan - Healthspan deteriorates along 3 vectors as we age: Cognitive decline, physical decline, emotional decline. The way to prevent this under Medicine 3.0 is:
1. Exercise
1. Cardiorespiratory (a.k.a. aerobic) fitness
1. Peak aerobic fitness: Measured by VO2 max (peak amount of oxygen your body can consume per KG of body weight per minute measured in millilitres). Probably the single most important biomarker for longevity, increasing it makes you functionally younger. Improved by training at high levels of intensity (but short of HIIT), suggested that one performs a working set (running, cycling, swimming etc.) for four minutes, then rest for four minutes, perform 5-6 sets, once a week.
2. Aerobic efficiency: Measured by power output (in Watts) per KG of body weight in heart rate zone 2. Improves mitochondrial health which is critical for longevity. Zone 2 training is foundational for the rest of healthspan improving initiatives that one might undertake. At a minimum one should do 3 hours per week of zone 2 training.
2. Muscle mass and strength: Muscle mass begins to decline as early as our thirties, and worse, muscle strength deteriorates even faster. Unchecked, it leads to sarcopenia. Important to measure bone mineral density (BMD) using a DEXA scan as it is another good metric to check for weakening strength. Counter this decline by strength training:
1. Train grip strength: Dead hang for 120 seconds for men, 90 seconds for women. Bonus points if the bar can rotate freely. Training to carry heavy stuff over reasonable distances/time: Like 30%-35% your body weight (as a back pack if you wish) for 5KM. Or half your body weight in each hand (like dumbbells) for a minute. Rucking is another thing one can do as it combines many benefits into one.
2. Train concentric as well as eccentric motions: How slowly and under control can you lower a weight.
3. Pulling motions: Chin-ups, pull-ups, rows etc.
4. Train hip hinging movements: Deadlifts, squats, step ups, lunges, hip thrusts etc.
3. Stability
1. If you get injured, then you are out of the game (of longevity) for some time. The older you are, the longer you will be out. And this time "on the bench" can cost dearly. So do not get injured.
2. The way to do this is to train for stability. The author defines stability as our subconscious ability to harness, deaccelerate, or stop force. This can be tricky because, as I alluded to earlier, the body is a compensation machine and it can make you believe you are stable in an area where it is just utilizing other structures to bring about the desired result, but when these structures fail as they inevitably will with time and age is when one realizes the critical importance of training for stability.
3. Stability training based on principles of dynamic neuromuscular stabilization (DNS)
2. Nutrition
1. Think of it as "nutritional biochemistry", a system whose end goal should be:
1. Are you under or over nourished?
2. Are you under or adequately muscled?
3. Are you metabolically healthy?
2. We know very little with certainty about nutritional biochemistry because food and what it does to our bodies is enormously hard to study since it is affected by our environment, culture, apart from a person's genome and microbiome in complicated ways. Basically, people or publications telling you the "truth" about a diet of a food have to be taken with a grain of salt.
3. What we do know, however, are some fundamental truths
1. Don’t eat too many calories, don't eat too few. Get sufficient protein and essential fats. Cook your food to be on the safer side.
2. If your great grandmother would not have recognized it as food, then don't eat it. Home cooked food is generally better. Prefer to eat native, locally and organically grown whole foods.
3. Our ancestors, who evolved to be omnivores, got to sample sugar (in the form of honey or fruit) only occasionally through the year, keep it that way. On a related note, fat and not carbs were their primary fuel source, try to get there in ways that are suited to your body and lifestyle. Also, winters were a time of reduced intake and increased reliance on fat stores, while spring and summer were relatively abundant times - try to track your overall macros to this pattern if possible.
4. Yes, you should track your macros:
1. Carbs: Use a CGM, keep average glucose levels below 100 and spikes (esp. those above 160 mg/dL) to a minimum.
2. Protein: Use traditional method of knowing approximately how much protein a food contains. Target 1g of protein per pound of body weight. Plant protein is less bioavailable than animal protein and has less of essential amino acids methionine, lysine, and tryptophan, potentially leading to reduced protein synthesis. So you may need to have more of it and be more deliberate if choosing to only consume plant protein.
3. Fat: Monounsaturated fatty acids (MUFA) are the best kind of fat, so extra virgin olive oil and other MUFA rich sources should constitute most of your daily fat intake. Then, polyunsaturated fatty acids (PUFA) have a slight edge over saturated fatty acids (SFA) but both can be consumed in low-moderate amounts without harm for most people. Apart from this make sure you consume EPA and DHA supplements in capsule or oil form unless
3. Sleep
1. Chronic sleep deprivation will wreck your health no matter what you may be doing otherwise to keep it in top shape.
2. Generally, we need to sleep 7.5 to 8.5 hours each night. Babies, kids and teens need to sleep more. However, long sleep, going into the 10-11 hour range each night can also be a sign of problems (if you're and adult that is).
3. The quality of sleep is as important as the quantity. There are tests that can help you figure that out: Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Insomnia Severity Index, STOP-BANG, and there are the many wearable tech devices out there too that can help provide a reasonable (but not perfect) assessment of sleep quality.
4. How to get better sleep in general:
1. Keep the bedroom dark, cool and relatively quiet. Getting a warm bath/hot tub/sauna before bedtime is good.
2. Do not do mentally intensive/stressful work just before bedtime. Or more so, just do not do/watch/listen to things that can make you anxious or stressed like news, social media or gaming.
3. Avoid intense exercise 3 hours before bedtime. Do not eat anything (at least anything too heavy or rich) 3 hours before bedtime
4. Set times to go to bed and wake up, and stick to them. A wind-down routine where you signal to your body/mind that it is time to sleep can help like turning down the lights, getting a warm bath, turn down any noise makers, putting away the gadgets etc. Give yourself enough time to sleep, i.e. go to bed 8 or 9 hours before you need to wake up.
5. No alcohol before bed (it may help put you to sleep initially but then will wake you up in the night plus wreck your sleep quality)
6. No technology before bed if you can help it. No smartphones, tablets or laptops in the bedroom (and no TV either). Books are OK (maybe even a Kindle if you use it only for reading).
7. Have a good day: one that has productive work, exercise, times with family, friends, community, good healthy food.
8. If you can, don't use your bedroom for other things apart from sleeping. This way your body will naturally know it's time to sleep when you enter the bedroom (what James Clear calls "One space, one use").
9. Avoid naps during the day time, if you must have one then try 30-40 mins around 2PM.
10. Don't obsess too much about your sleep, your body knows how to get it you just get out of the way.
5. When sleep is genuinely hard to come by:
1. Stop fighting it, go do something relaxing till you get sleepy again.
2. Cognitive behavioural therapy for insomnia (CBT-I)
4. Emotional health
1. Basically, if you don't see a point in living then what is are all the longevity shenanigans worth anyway? Aside, poor emotional health (depression, misery, lack of purpose or meaning, lack of social connection etc.) can wreak havoc on your physical health too. Ergo, emotional health is as important as the other topics covered in this book.
2. Age has very little correlation with emotional health unlike the four horsemen.
3. Mental health and emotional health are not the same thing; the former represent disease-like state that manifest in predictable ways, while the latter has more to do with how we regulate our emotions and manage interpersonal relationships.
4. Unlike the recent societal focus on physical health, there continues to be a mix of stigma, ignorance and apathy towards caring for one's emotional health.
5. The different undesirable behaviours we exhibit as adults are adaptations to the traumas we suffered as children. Traumas can be big and small, the small ones may add up to a big trauma. They can be generally categorized under:
1. Abuse
2. Abandonment
3. Neglect
4. Enmeshment
5. (witnessing of) Tragic events
6. Children will adapt in the following ways:
1. Addiction
2. Co-dependency
3. Habituated survival strategies (like anger)
4. Attachment disorders
7. Techniques that one can use to improve their emotional health and balance
1. Think of your relationships like a delicate ecosystem that can thrive with the right behaviours and wither with the wrong ones. And using that view, care for the whole than just your ego.
2. Reframing: Looking at a given situation from someone else's POV to make sense of why things happened/are happening the way they are, including the fact that in the new frame, they (and not you) are the centre of their universe.
3. Eulogy virtues: Are you being the person at whose funeral their friends, family and acquaintances will have nothing but good things to say about?
4. Be kind to yourself: Just listen to your negative self-talk when you do something is likely to produce it; record voice memos on your phones but instead of speaking to yourself, speak how you would to a friend who just happened to mess up. Chances are that you would be much kinder and forward-looking. You can also send the recording to a therapist of a trusted contact to analyse and process later.3
5. Dialectical behaviour therapy: Modified type of CBT. Main goals are to teach people how to live in the moment, develop healthy ways to cope with stress, regulate their emotions, and improve their relationships with others.
5. Exogenous molecules - Unfortunately, these is not covered by the author in this book. But I hope he is able to write another one on them, I think they are powerful enablers to the Medicine 3.0 approach.
12. Potential longevity genes (list not exhaustive):
1. APOE: Codes for protein called APOE (apolipoprotein E) that is involved in cholesterol transport and processing, and it has three variants: e2, e3, and e4. e3 is the most common, having one or two copies of e4 seems to multiply risk Alzheimer’s, while e2, seems to protect against dementia).
2. FOXO3: FOXO3 belongs to a family of “transcription factors,” which regulate how other genes are expressed—meaning whether they are activated or “silenced.” When FOXO3 is activated, it in turn activates genes that generally keep our cells healthier. It seems to play an important role in preventing cells from becoming cancerous as well. FOXO3 can be activated or suppressed by our own behaviours. When we are slightly deprived of nutrients, or when we are exercising, FOXO3 tends to be more activated, which is what we want.

Notable quotes

• ... modern medicine does not really have a handle on when and how to treat the chronic diseases of aging that will likely kill most of us. 
• Medicine’s biggest failing is in attempting to treat all these conditions at the wrong end of the timescale — after they are entrenched — rather than before they take root. 
• One macronutrient , in particular , demands more of our attention than most people realize : not carbs , not fat , but protein becomes critically important as we age. 
• Exercise is by far the most potent longevity “ drug . ” No other intervention does nearly as much to prolong our lifespan and preserve our cognitive and physical function . But most people don’t do nearly enough — and exercising the wrong way can do as much harm as good. 
• ... need to think about and plan for the later decades of our lives — our seventies , eighties , nineties , or beyond. 
• ... this is how the centenarians achieve their extraordinarily long lifespans : they delay or prevent the onset of chronic disease , by decades compared to the average. 
• The short answer is that evolution doesn’t really care if we live that long. Natural selection has endowed us with genes that work beautifully to help us develop, reproduce, and then raise our offspring, and perhaps help raise our offspring’s offspring. Thus, most of us can coast into our fifth decade in relatively good shape. After that, however, things start to go sideways . The evolutionary reason for this is that after the age of reproduction, natural selection loses much of its force. Genes that prove unfavorable or even harmful in midlife and beyond are not weeded out because they have already been passed on. 
• Put another way, if we want to outlive our life expectancy and live better longer, we will have to work hard to earn it — through small , incremental changes. 
• While your genome is immutable, at least for the near future, gene expression can be influenced by your environment and your behaviors. 
• You’d think that hunger might be unhealthy, but the scientists have actually found that the less they feed the animals, the longer they live. 
• ... long - term severe caloric restriction is difficult if not impossible for most humans to sustain. 
• ... no evidence that extreme CR would truly maximize the longevity function in an organism as complex as we humans ... 
• A small but growing number of people, including me and a handful of my patients, already take rapamycin off - label for its potential geroprotective benefits. I can’t speak for everyone, but taking it cyclically does appear to reduce unwanted side effects, in my experience. 
• We have a far greater capacity, almost unlimited, for storing energy as fat ... 
• ... subcutaneous fat, the layer of fat just beneath our skin — is actually the safest place to store excess energy. 
• Insulin is all about fat storage, not fat utilization. 
• High uric acid is an early warning sign that we need to address a patient’s metabolic health, their diet, or both. 
• But the first thing I look for , the canary in the coal mine of metabolic disorder , is elevated insulin. 
• I would go so far as to argue that early detection is our best hope for radically reducing cancer mortality. 
• The problem is that we’re still not very good at detecting cancer in these early stages — yet. 
• We need to think in terms of stacking test modalities — incorporating ultrasound and MRI in addition to mammography , for example , when looking for breast cancer. 
• The key insight was that robust blood flow seemed to be critical to maintaining brain health. 
• Another compelling and perhaps parallel theory of Alzheimer’s disease says that it stems from abnormal glucose metabolism in the brain. 
• Just like reduced blood flow, reduced glucose metabolism essentially starves these neurons of energy, provoking a cascade of responses that include inflammation , increased oxidative stress, mitochondrial dysfunction — and ultimately neurodegeneration itself. 
• This is also one area where a ketogenic diet may offer a real functional advantage: when someone is in ketosis, their brain relies on a mix of ketones and glucose for fuel. Studies in Alzheimer’s patients find that while their brains become less able to utilize glucose, their ability to metabolize ketones does not decline. 
• I now tell patients that exercise is, full stop and hands down, the best tool we have in the neurodegeneration prevention tool kit. 
• Our genes no longer match our environment. Thus, we must be cunning in our tactics if we are to adapt and thrive in this new and hazardous world. 
• ... each of us needs to be training for the Centenarian Decathlon. 
• ... millions of years of evolution that have optimized us to be highly efficient fat - storage vehicles. 
• Alcohol serves no nutritional or health purpose but is a purely hedonic pleasure that needs to be managed. 
• ... everyone tends to be more insulin sensitive in the morning than in the evening , so it makes sense to front - load our carb consumption earlier in the day. 
• ... try to eat more than fifty grams of fiber per day. 
• ... aerobic exercise seems most efficacious at removing glucose from circulation, while high - intensity exercise and strength training tend to increase glucose transiently ... 
• ... good versus bad night of sleep makes a world of difference in terms of glucose control. 
• ... frequent, prolonged fasting may be neither necessary nor wise for most patients. The cost, in terms of lost lean mass (muscle) and reduced activity levels, simply does not justify whatever benefits it may bring. 
• But fasting can still prove useful sometimes , in some patients — generally, patients for whom no other dietary intervention has worked. 
• I once believed that diet and nutrition could cure almost all ills, but I no longer feel that strongly about it. 
• Stop overthinking nutrition so much. Put the book down. Go outside and exercise. 
• ... long sleep is also a sign of problems. 
• “If you want to find someone’s true age, listen to them. If they talk about the past and they talk about all the things that happened that they did, they’ve gotten old. If they think about their dreams, their aspirations, what they’re still looking forward to — they’re young.” 

In closing

For a first-time writer, I think Outlive is a decent attempt and goes into enough detail to get someone more than casually interest in health and longevity motivated to read till the end. I found the coverage of the "four horsemen" adequate and quite well explained for the average reader, the foundations of exercise, nutrition and sleep were also reasonably covered and should provide the interested reader a blueprint to design a system around.

However, there were places where I felt Peter could have gone deeper; the parts on emotional health seemed too focused on manifestation of childhood trauma in adults (where professional intervention may be the most appropriate recourse), and left out the more mundane practices such as gratitude, meditation and finding purpose that can be used by average anybody (whether suffering from childhood trauma or not). Of course, exogenous molecules from mainstream multivitamin tablets to niche nootropics would have been a good area to cover and I think many readers would have found this omission unnecessary.

Overall, I think it's a good book to add to one's knowledge base and is a good read for 2023 in the health and longevity space.