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The Best Introduction To The Science Of Longevity: A Review of Outlive

Dr. Peter Attia and Bill Gifford have given us actionable ways to live healthier lives

https://www.amazon.com/Audible-Outlive-Science-Art-Longevity/dp/B0B64WL9PK/ref=sr_1_1?crid=9UCC5YRZ7B37&keywords=outlive&qid=1688859652&sprefix=outlive%2Caps%2C151&sr=8-1

Why Outlive Outperforms

Outlive is a rare book. It combines a depth of perspective into physiology with well-formed critical analysis in readable prose. The science Dr. Attia and Bill Gifford present is clear, easy to understand, and applicable to the reader’s situation almost no matter what that situation happens to be. The introductory book about longevity has long been something I thought of as a holy grail because it seems almost impossible to write such works without making errors that lead the reader astray. Dr. Attia has provided just such a book, blending beautifully presented, easy-to-grasp science with deep novel insights that most people should be able to apply in whole or in part to their lives.

In a post-covid world where body issues are so often more than skin deep, Outlive is a wealth of relevant insight designed to empower the reader to make reasonable life adjustments in the interest of personal longevity. Dr. Attia has performed the critical portions of his research with adequate care, bringing back reasonable questions and, rather than dogmatically presenting one particular way to proceed, taking the time to explain the rationale for acting. This approach empowers the reader to plot their own path forward by applying the principles in context and observing the outcome.

Outlive is a book that provides the right background for us to get a sense of what our bodies are doing as we navigate our increasingly complex modern world. Released in 2023, Outlive is a great read and it gives you actionable information about how your body works, empowering you to have more control over your health and build a better life. This review will share my deep connection to the work and all the reasons I think everyone should read it, as well as a bit of discussion about the message of the book including the pillars of longevity and my favorite high-level takeaways. Finally, we’ll close with a brief note on Dr. Attia’s approach to preventing each of what he calls the Four Horseman diseases of ageing.

An Approachable Introduction To Longevity Science

I first began to follow Peter Attia’s podcast, The Drive, in 2018 or 2019. My career had taken a sudden turn in 2017, after years of graduate study ended without a meaningful career opportunity in my field. I wrote the bulk of my first peer-reviewed book during the first part of 2017, started my first startup, and then almost immediately when Dad’s diagnosis came in I got a remarkable opportunity to pivot into biotech. I’ve been following Dr. Attia since early in that journey. In my opinion, the hardest thing about medicine today has little to do with what is known and much, much more with how widely and/or effectively that knowledge is shared. Dr. Attia is one of the best out there in terms of his ability to stick to accepted science, of which he has a more than adequate grasp, and as a bonus he also has that rare gift: the ability to make things easy to understand.

This book meant a lot to me because it does something I tried to do better than I could have. I got pulled into medicine and biophysics after receiving my M.A. in applied philosophy and ethics almost a decade ago. The summer of 2017 terrified me: my dad was diagnosed with cancer and had a kidney surgically removed. 

I knew that cancer could be hereditary, so the fear of losing a loved one and the fear that my own behavior was potentially leading me down the path to early death and disability blended together in my mind, creating a powerful reality check that forever changed the trajectory of my life. Worse, there was nothing to be done for it. I had two options if I wanted to help: cure cancer or make a lot of money to pay for the best treatments. Mortality proved itself real and I found myself pulled out of more theoretical pursuits such as the explanation of consciousness, only to be thrust headlong into a new research project about the possibility of extending the human lifespan.

There I was, a philosopher, chasing answers to a question we could label an application of conscious thought to extend the health of the body.

When I met my former employer, a man in his 60’s who recovered from end stage renal disease after studying physiology and taking corrective action that was much in-line with the conclusions one can draw from Outlive, I was skeptical. The idea that one concept could hold the key to all of human health was too much for me, but then life happened. A year passed. Funds were raised. The plan shifted, instead of a book we decided to go into the lab. Suddenly, I was hired as Director of Research in 2018, the startup’s first employee. It was official: I had studied philosophy all my adult life only to grow up to become a scientist. 

I had been a researcher before, and I knew the drill. I read thousands of scientific papers, constructed highly detailed maps of physical processes such as the way the albumin protein moves through the body, and even skipped a chance at a free South by Southwest badge to instead build a bunch of cabinets and install them in the location that was to become our lab. I was hooked with no questions asked! Soon, my entire life was oriented to the North Star: developing a longevity-oriented understanding of the human body to push past what Dr. Attia calls Medicine2.0 and into more rewarding territory. 

Prevention, diet, exercise — for our team, there was one pathway that led to chronic disease and our goal was to understand it in as much detail as possible so that our therapeutic agent could corner the market by improving the lives of everyone who bought it. We studied the interior surface of blood vessels, learned about the complexity of the blood — which it is still impossible to study in vivo, by the way! — and worked on a way to improve its ability to transport oxygen and nutrients to each of a human body’s 37 trillion cells.

During this time, I studied nutrition intensely, as well as a variety of other aspects of health and sciences. These explorations ranged from microbiology to colloidal chemistry and everything in between. My mission was to prove out — true or false — a theoretical model of the body that predicted the progression of chronic disease and could yield new, more powerful therapies based on physics. I left the startup in late 2019 when it became clear that our trajectory was unlikely to lead to success and that pivoting was not going to work, but I barely slowed down in terms of reading and I never stopped following Dr. Attia’s podcast. After all, I was convinced that this science could help me and everyone I care about live a better, healthier life.

There were issues along the way. Primarily, I lack the qualifications of a doctor of medicine (MD) degree — in fact, I’m a mere master of philosophy, not a doctor of anything! This means there are some areas where my background could be a bit stronger, but in general I find that the depth of my knowledge in relevant fields turns out to be sufficient most of the time. When I find a gap, I make haste to fill it in. In general I am well-informed about the things I need to know. Just as Dr. Attia’s expertise in engineering and math come in handy in his medical practice, my habit of reading musty old tomes prepared me to rabidly absorb a lot of new words and think advanced abstract thoughts about the way they relate to one another.

Despite the success we achieved in understanding something important and coming up with ways to test it, at my old company we weren’t able to reach the milestone we were looking for during the time we had available to us. 

Nonetheless, an inkling remained lodged in my mind: the idea that understanding a few key principles of the metabolism could lead scientists to create effective treatment and prevention methods for dealing with chronic diseases that Dr. Attia refers to as the Four Horsemen. 

Everything was visible in the blood vessels, but how to manipulate it? 

How could we improve it when we saw that it was in a bad way? 

My former employer’s answer was unable to deliver results, but Dr. Attia manages to provide a powerful plan of action as well as a few hypothetical ways treatment could be improved. By reading Outlive, you’ll be able to achieve a higher level of understanding of not only the state of medical science today but also what you are able to do about it. For me, this has felt like a relief. Since my first listen to the audiobook, I have spent sixteen weeks running progressively faster 5km jogs in the evenings here in dry Lubbock, Texas. I feel that I have better control of my body now that I understand how to manage my blood glucose level, which I learned from Dr. Attia by reading this book. The research here is strong and even better, there is useful information on every page.

What stands out most to me about Outlive, and the reason I’ve listened to the audiobook a dozen times by now, is the way it takes an idea very similar to the complicated old project from my former startup and compresses it. Rather than a universal health biomarker, it seeks to explain the science we already have to the people who need to understand it. People then are tasked with taking charge of their own health and many who choose to take this approach seriously do quite well. 

What is the approach? 

Well, it all boils down to the five pillars of longevity.

The Five Pillars Of Longevity

These five items are the key points Dr. Attia makes in Outlive. Most of the discussion of stability, for example, ties into the Fitness pillar here. Knowledge is the key animating force here, as understanding the things going on under the hood enables us to make better choices to keep from sending the system out of alignment. Let’s take a quick peek at each one, but don’t forget to read the whole book to understand completely.

1. Happiness/freedom from malaise

Emotional health is tied to hormones that regulate mood. Cortisol, a stress-related hormone, is elevated in people who experience stress. Exercise can help to modulate excess levels of cortisol, and in this simple feedback loop we can see that, like a grounding rod in a lightning storm, stress can be relieved by physical activity. 

The payoff here is perhaps best: we feel happy when things work together to enable us to achieve the main benefit of good health, improved mood. Noticing the impact that the fitness routine and diet have on how we feel is perhaps the single most powerful motivation to keep putting in the effort to make the good choices.

2. Fitness/Freedom from injury

Just as exercise is important to support mood regulation, fitness is important to support exercise. Stability and adequate muscle can help the body manage hormone levels to improve a person’s ability to tolerate stressful life circumstances or painful emotions, but only if activity is possible. 

If injury compromises our ability to exercise, we lose the metabolic benefits of that missed exercise — we burn fewer calories, our hormone balances change, and far-reaching consequences can be seen throughout the body as our condition deteriorates in response to our inactivity.

3. Knowledge/ability to consciously manage health

Dr. Attia’s book does us a great service by accurately stating the facts and providing a high-level view of what the science has been bearing out in terms of conclusions from all of this research that has been going on. By understanding the way our body works, we can exercise to prevent injury or even to restore function to our body after a period of recovery from, say, a shoulder injury. Responding effectively to pains and aches that signal to us that our body has problems is as important as optimizing routines and workouts to minimize the risk of creating new problems by pushing too hard and getting hurt.

Keep in mind that knowledge of our metabolism may also empower us to compensate for an injury by eating more protein and fewer carbohydrates, sleep more, and even find new modes of exercise to work around our injuries and minimize the damage.

4. Nutritional biochemistry as a contextual practice

Nutrition is, Dr. Attia points out semi-regularly in the text, mostly about getting the right amount of the various macronutrients you need: fats, carbohydrates, and proteins. The most important part of nutrition today is knowing what to avoid, contrary to much of our species’ history. We leave the text with an understanding of how important it is to deviate from the SAD (standard American diet) and how to structure our own custom macronutrient intake throughout the day to meet our goals. 

Once we have been disabused of any favor we had for caloric restriction by Dr. Attia’s literature review in Chapter 5, the idea to consume our carbohydrates early in the day and before exercise appears. Proteins and fats can be consumed instead of carbohydrates later in the day, when the glycemic response is elevated. These principles enable us to flatten our glucose response and presumably benefit from improved mitochondrial and metabolic health. 

I bought a finger stick kit for $20 and have been testing my glucose levels periodically, fine-tuning my diet to complement my new workout routine. Knowing what caused my glucose to spike before enables me to manage it more effectively moving forward, and I’m considering asking my doctor for a continuous glucose monitor (CGM) to get a better idea of what’s going on. 

5. Sleep as non-negotiable

I didn’t say it, but I’ll repeat it. Sleep is not negotiable. It is a required component of health in terms of metabolism, mood, stability, and the ability to exercise. Sleep has an impact on our insulin response to food and also upon our ability to perform in mental and athletic tasks, underscoring the utter centrality of getting enough sleep to our metabolic health. Dr. Attia explains the differences between various drugs, some of which simulate unconsciousness without providing the benefits of real sleep.

Medicine3.0

In a way, Dr. Attia also excels my old team and former project in terms of integration. Outlive critiques Medicine2.0 on occasion, and rightfully so, but what it does not do is invent a lot of new terminology (aside from perhaps the Centenarian Decathlon). If you took your health courses seriously in college, you should be able to understand most of the high points here.

The simplicity with which it’s brought back to the reader is a two-edged sword. On the one hand, if you do it well, you reach a larger audience and benefit more people by writing. On the other, it’s much easier to get things wrong when attempting to communicate at max simplicity. Outlive does an exceptionally good job on both fronts. So much so that it is impacting the way I am approaching projects that aren’t necessarily direct tie-ins. Even as I write this book review, I’m thinking a lot about Worldview Ethics and how moral philosophy can benefit from application of physiological science.

Put simply: Health is a pillar of the good life. Insulin resistance and the sugar metabolism more broadly are pillars of the modern scientific understanding of diseases that happen alongside ageing. In some sense, a lot of my best research work over the years has happened because I pay attention to my environment and make adaptations accordingly.

Following Dr. Attia through his journey in Outlive has brought me both a stronger sense that I have the ability to make good choices and live a healthier life as a result, as well as a sort of closure in my prior ageing research journey. The closure comes from the simplicity, the sheer obviousness of the sugar metabolism as an explanatory tool in the light of what is known about the diseases of ageing. The sense that I have more control over what happens to my body comes from Dr. Attia and Bill Gifford’s meticulous work on a problem I tend to gloss over as I focus more on the theoretical side of things, i.e., the problem of what to do about this.

Whether you’re seventy or seven years old, reading this book can change your trajectory and help you find your way forward into a better future.

Top 6 Takeaways: What Outlive Changes

These takeaways are the parts that resonated most with me. They are the things I point out when I share the book with friends and family, in hopes of inspiring better life for those I care about. The general function of the work of Dr. Attia is to distill actionable yet correct concepts from the body of scientific literature for application in daily life, and the work is a stunning success.

While there is no silver bullet to take ageing completely out of the scope of things we need to worry about as time goes on, the progress Outlive offers is entirely real. We learn nothing that is not well-backed in the scientific literature and each discussion builds toward the book’s primary goal: better, healthier ageing for anyone who can apply the principles found in the book to real life.

1. 30 minutes of Zone 2, 5x/week. Every week.

Zone 2 cardio enables the muscles to pull glucose molecules out of the circulatory system. The muscles break down the glucose and instantly put it to work powering physical activity. Exercise outperforms FDA-approved small molecule therapeutic approaches rather often in clinical trials cited by Dr. Attia in the text, highlighting the power this mode of activity has for transforming the body. Pulling excess glucose out of circulation and giving the vasculature a chance to clear out the cobwebs at the same time is a win-win, but exercise also releases endogenous drug-like chemicals that lead to a sense of happiness and well-being.

2. There is no “true” diet — eat by principle.

What are you noticing in your body? Do you run out of energy at a certain time of day? You can use a cheap insulin monitor to get a feel for what’s happening to your blood sugar and then re-formulate your diet, giving yourself the opportunity to generate measurable data to then observe as you experiment with different combinations. You can tweak your diet to include extra sugar to power some pre-marathon subcutaneous fat storage or limit excessive carbohydrate metabolism by cutting out sugary drinks.

Once you understand the principles, you may find yourself sticking mostly to morning time carbohydrate consumption and eating more fats & proteins later in the day. The goal is to develop an understanding of what’s happening in the body and provide yourself enough data to begin to make informed choices about what to eat, giving you even more control over the way you feel.

3. Insulin resistance is a major risk factor for chronic diseases of ageing.

Is it a coincidence that the lifestyle risk factors for diabetes also contribute to risk for the other Horseman diseases? The same biomarkers that help combat the severe insulin resistance we call type 2 diabetes will also have a positive impact in our efforts to prevent atherosclerosis, Alzheimer’s Disease, and cancer. In the end, it appears that there is a biomarker of ageing, just as my lab used to search for. It’s just that insulin and glucose provide more information than we realized back then. Dr. Attia’s work in Outlive is as remarkable for its accuracy in chronicling the history of sugar as it is in providing suggestions for how to manage this remarkable chemical we all have such unfettered access to today.

4. Preventing injury is more important than setting records.

If you get hurt — no matter who you are — you’re likely to come back at a lower level of fitness than what you’d achieved prior to your injury. It is more important to avoid injury during a workout than it is to set a new personal best every time we enter the gym. Taking a long-term mindset approach is crucial to maintaining a high level of personal fitness precisely because priorities such as the avoidance of injury can be clearly seen in terms of their real importance. Keeping up with your buddy or neighbor is not as important as staying fit over the long term.

Dr. Attia’s innovation here, the Centenarian Decathlon, sets the appropriate life-long scope of perspective. As a Centenarian Decathlete, the goal is the best possible health for the longest possible time.

5. Sleep is as important as nutrition or exercise — you cannot be healthy without it.

No fitness plan is complete without careful attention paid to sleep. The normal pointers are all available: make sure it’s dark, tell yourself it is okay to sleep, get enough uninterrupted sleep if possible, and last but certainly not least — take it easy on the food if your sleep is disturbed, especially if your exercise is also disturbed. Certain medications for sleep don’t yield all the benefits we need to get from our rest, so be careful when choosing sleep aids.

Sleep ties into health in a complicated way. Getting less sleep than you need can slow down your metabolism at the cellular level by making your cells less receptive to insulin. Eating sugar in a sleep deprived state can therefore induce a big spike in blood sugar levels, causing the body to store fat and providing opportunity for more serious issues to arise. It’s best to steer toward proteins and fats if missing sleep is unavoidable.

6. The best fitness plan comes from within.

We each need to take up responsibility for our own fitness. Outlive helps us start with a foundation built upon an understanding of the core principles of health.

a. Exercise should fit you. You need to find something you can enjoy, and that works well with your lifestyle.

b. Sleep hygiene is important to all aspects of health. We should give ourselves permission to sleep and sleep as best we can.

c. Food is medicine and medicine is food. Eat a diet that you enjoy that arranges macronutrient delivery to suit your needs.

Preventing The Four Horsemen Of Ageing

Preventing ASCVD (Atherosclerotic Cardiovascular Disease)

Of the four Horseman diseases, ASCVD is the easiest to prevent, according to Dr. Attia. To prevent ASCVD, our strategy is simple: do not smoke and do effectively manage your metabolic health along the glucose/insulin axis. What this means is that glucose spikes are to be avoided if possible, by using all tools at our disposal: exercise, sleep, and nutrition can all play a role here.

When Dr. Attia says that the easiest of the Horseman diseases to prevent is ASCVD, he doesn’t mean that ASCVD is simple or easy to prevent in its own right. Rather, the point is that, for individuals willing to take charge of the metabolic processes in their own bodies, ASCVD risk is easier to mitigate than cancer risk or dementia risk. In some cases this involves doctors and drugs, but for most of us simply paying careful attention to our metabolic health will pay major dividends.

By not smoking, getting plenty of exercise, maintaining muscle mass, and building a high VO2 Max, we’re building up the number and power of our mitochondria. These engine-like organelles power our metabolism throughout our body by processing sugars and fats to generate ATP. It’s fairly safe to say at this point that a healthy cellular powerhouse is required for the state of organism-wide health we’re all striving to build and maintain.

The Best Odds Of Preventing Cancer

Cancer cells exhibit a unique metabolic arrangement, which Dr. Attia’s extensive reading of the literature suggests could be related to the need of the cell to procure a massive amount of new building materials to fuel its reproduction. Whether cancer is a metabolic or genetic phenomenon, using exercise to maximize mitochondrial health mitigates the risk by minimizing mutations on the one hand and by improving metabolism on the other.

As Dr. Attia points out, the relevant pathway is fairly simple: inflammation caused by normal physiological processes such as the inflammatory cytokines given off by dying fat cells in obese bodies induce cells to become cancerous. Smoking and other sources of inflammatory processes that are known to be carcinogenic could be causal agents toward the increase of cancer risk by this mechanism. Once cells have become cancerous, PI3K is activated by insulin and IGF-1, enabling the voracious appetite for glucose demonstrated by cancer cells. In this light, a problem I used to be very interested in — the metabolic theory of cancer — seems somewhat irrelevant. The treatment is the same whether the cancer process is driven by metabolism or by mutation.

Insulin production is increased by the pancreas when high-sugar diets are eaten and sustained insulin overproduction is the body’s first response to insulin resistance, which would explain the uptick in cancer risk for obese or metabolically unhealthy individuals. The cancer cells don’t develop insulin resistance. Instead, they fuel their perverse growth by capitalizing on the insulin resistance developed by other cells. More insulin in circulation means the tumor cells have more ability to pull in glucose from the bloodstream to replicate and power themselves.

This aspect of cancer has also been used as a treatment vector in the lab: Attenuating the PI3K pathway by lowering insulin seems to slow cancer growth! Despite the lack of conclusive evidence that all cancers will succumb to metabolic attacks like lowering insulin levels systemically, Dr. Attia points out that preventing cancer by avoiding the spectrum of insulin resistance is a logical place to start when we’re young. For example, smoking is known to increase insulin resistance, just as drinking large amounts of fructose does. If I were to conjecture, I'd wonder whether perhaps when people combine the two they unwittingly multiply their risk. To me, the call seems easy: it is better to simply flatten one’s glucose curve and feel better while minimizing unnecessary risk.

Stopping Alzheimer’s Disease Before It Starts

Alzheimer’s Disease (AD) is less well-researched than ASCVD or cancer, but the parallels between this and the other Horseman diseases are nonetheless quite apparent throughout the research. The risk factors for AD are, perhaps unsurprisingly, plausibly metabolic in nature. Our prevention regime for AD needs to involve not smoking, getting adequate nutrition, and being active in a training routine that consists of exercise we enjoy that trains Zone 2 and fosters our stability.

Seeing a trend?

There is one goal for us, here, across all four of the Horseman diseases.

Alzheimer’s Disease is occasionally referred to as “type 3 diabetes” because the buildup of amyloid and tau proteins has a deleterious metabolic effect that is observed in all clinical cases researchers study, essentially choking out the affected neurons and shutting them off so that they no longer efficiently communicate with others. This is where the holes in conscious behavior originate. Not only does regular exercise reduce our body’s dependence upon insulin, including the brain, but it also has the ability to generate lactate. Lactate is a fuel that our neurons can use via the ANLS (astrocyte-neuron lactate shuttle) pathway to power metabolic function in a pinch, just like keytone bodies.

In the end, preventing Alzheimer’s Disease is very likely most achievable by managing metabolic health effectively over the course of our lifetime, just like cancer and ASCVD.

Preventing Diabetes with Zone 2 Cardio & Smart Carbohydrate Timing

Preventing Type 2 Diabetes is not just possible, it’s a direct result of the diet and exercise regime advocated for in Outlive. With diabetes, the most striking relationship between glucose metabolism and insulin resistance is visible. Eating sugar without understanding what it does to the body is in some sense the direct cause of the diabetes epidemic, which may ultimately turn out to be a driving force behind the other Horseman diseases as well.

Mitigating the spikes in insulin that result from our behavior when we eat too many carbohydrates in the wrong situation is a complex task, but awareness of the principle is often enough to encourage better sugar management in continuous glucose monitor users. Most people can get by without the need for glucose monitoring by applying the principles derived from glucose monitor studies and nutritional biochemistry.

In essence, the goal is to flatten the insulin response so that the pancreas does not need to overproduce insulin just to lower the blood sugar after a meal. This simple tactic can prevent negative biological processes such as storing fat in visceral tissue where it does not belong, dips in blood sugar causing postprandial fatigue, and even unsightly blemishes such as skin tags (which trace their origin to hyperglycemic conditions!). You won’t find a reference to skin tags in Outlive, but I made a living studying the deep connections between the various diseases of ageing for years and I fully back Dr. Attia’s read of the state of affairs he addresses in his medical practice and his writing because the root issues are so thoroughly considered.

For my part, Outlive is the book that I think everyone alive should read carefully. By maintaining the insulin/sugar metabolism, we set ourselves up to live longer, fuller, more fulfilling, and most of all, happier lives. Representing a new level of applicable science, Outlive is an exceptional book because it concisely teaches us how to get there without overwhelming us.

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