Notes from Outlive: The Science and Art of Longevity by Peter Attia

Most books on health and/or fitness tend to focus on one isolated aspect. Either they refer to one very specific type of diet or to an exercise regimen. Even within the books that are credible, it’s crazy how much contradictory evidence is out there.

The problem is our bodies are varied, and what works for one person doesn’t necessarily work for another.

Then, there are a lot of books that are just plain wrong and potentially harmful for just about anyone.

Outlive: The Science and Art of Longevity by Peter Attia MD is not such a book.

I first came across Dr Attia in 2017, on the Invest Like the Best podcast. He spoke of “healthspan” – the span of your life where you’re healthy enough to do the things that matter to you. The image below summarises the role of healthspan. (I had to go looking on waybackmachine for an older version of this very site where I had written a post on the topic of that 2017 podcast Peter Attia – How to Live a Longer, Higher Quality Life.)

Longevity means maximising healthspan and lifespan

It was a no-brainer for me to read Outlive. For one, it’s not one of those books that could’ve been a blog post because it does not take one central concept and then fill out a book with it. The book is 17 chapters of high information-density, going from principles and strategy to tactics to live a longer and, more importantly, healthier life.

It talks at length about the root causes of the “four horsemen”, the major killer diseases: cardiovascular disease, cancer, neurodegenerative disease, type 2 diabetes and related metabolic dysfunction. The potential links between metabolic syndrome and everything else that goes on inside our body (and brain). The role of nutrition and exercise. He calls exercise “by far the most potent longevity drug”.

My notes from the book would make a short book by themselves, such is depth and breadth of information. Instead, I’ll try and capture the key points in this post, emphasise some chapters more than others. And I also highly recommend that you read the book.

Thinking Prevention not Cure

Medicine, the way it has been for the last few decades, is incomplete because it treats chronic problems (heart disease, diabetes) the same way as it does acute problems (broken bones, infectious diseases). So it deals with problems after they present themselves.

This makes sense in the case of treating a broken bone but is too late for chronic diseases that take decades to develop before they present themselves. Since medical education the world over has little to no focus on fitness and nutrition, it might be a while before it catches up to play a preventive role in chronic diseases. So we, as consumers of medical care, need to take a more proactive role in taking charge of our health and identify the lifestyle changes needed to maximise our odds of living healthier.

There are four major chronic diseases that account for the majority of deaths: heart disease, cancer, neurodegenerative disease, and type 2 diabetes and related metabolic syndrome. Except for heart disease, mortality rates from these haven’t declined significantly over the last several decades. The reason is that they don’t pop up when we’re in our 40s but take decades to develop. The good news is that these major chronic diseases share common features and drivers that we can mitigate, with a set of common actions and behavioural changes. This book is primarily about those changes.

When examining the evidence from observational studies and randomized control trials, its important to remember that “In Biology, we can rarely prove anything definitively the way we can in mathematics.”

“In the absence of multiple, repeated, decades-long randomized clinical trials that might answer our questions with certainty, we are forced to think in terms of probabilities and risk. In a sense it’s like charting an investment strategy: we are seeking the tactics that are likeliest, based on what we know now, to deliver a better-than-average return on our capital, while operating within our own individual tolerance for risk.”

Lessons from centenarians: Luck and a few genes

There are few comprehensive studies tracking centenarians over decades of their lives, so most “data” can be anecdotal. From one of the studies it turns out that “centenarians are no more health-conscious than the rest of us. They may actually be worse.”

The oldest of these die from pneumonia and other opportunistic infections, but the vast majority succumb to diseases of aging – the Horsemen – just like the rest of us. But the crucial distinction is they tend to develop these diseases much later in life than the rest of us – if they develop them at all.

It must be the genes? But analysis of thousands of centenarians to see which individual genes stand out as most prevalent came up empty-handed. While there are a few genes that confer advantages, for example, the APOE e2 variant protects against dementia, or cholesterol-related genes (CETP and APOC3) that are correlated with extreme longevity, no two centenarians follow the exact same genetic path to reaching extreme old age.

There is no such thing as the “perfect centenarian genome” because evolution doesn’t care if we live much longer after reproducing and hence does not specifically select for traits that enable long life, or deselect traits that do the opposite.

This is actually good news: we are not dependent on the outcome of a genetic lottery and can do things in our control.

Eat less, live longer?

Lab experiments on various species, including mice, yeast, worms, flies, fish, hamsters, and dogs, have found that restricting caloric intake lengthens lifespan.

While it’s not conclusive to say the same carries over outside of lab conditions, and especially to humans who live in a much more varied environment, “CR (Caloric Restriction) studies have helped uncover critical cellular mechanisms related to nutrients and longevity.”

Restricting the amount of nutrients available to a cell seems to trigger a group of innate pathways that enhance the cell’s stress resistance and metabolic efficiency – all of them related, in some way, to mTOR

mTOR (mechanistic target of rapamycin) is an intracellular protein complex. When food is plentiful, mTOR is activated, and the cell goes into growth mode, producing new proteins and undergoing cell division. When nutrients are scarce, mTOR is suppressed, and cells go into a more fuel-efficient and stress-resistant mode, activating a cellular recycling process called autophagy which means “self-devouring”.

The reason this seems to be good for us is apparently, in the constantly fed state, our cells keep growing and dividing. The old cells that have stopped dividing, but have not died, secrete a toxic cocktail of inflammatory cytokines, chemicals that harm surrounding cells. Going into “conserve and recycle” mode causes these old cells to be broken down, thus reducing systemic inflammation in the body.

Restricting the amount of nutrients that are available via dietary restriction or exercise triggers the production of newer, more efficient mitochondria to replace old and damaged ones. These fresh mitochondria help the cell produce more ATP, the cellular energy currency, with the fuel it does have.

The overall effect of restricting calories seems to be similar to that of the drug rapamycin, which reduces systemic inflammation by modulating the immune response of the body. This ties in with what I’ve come across in more than one source, that rapamycin could be a potential longevity drug sometime in the future.

There’s a growing body of evidence on the benefits of time-restricted feeding, something I started a few years ago and have seen measurable improvements across the board from lipid profile to energy levels.

I recommend listening to this video to get the basics about time-restricted feeding and the ways to implement it.

Metabolic Syndrome: Thin doesn’t necessarily mean healthy

Our metabolism is a function of the delicate task of maintaining the right amount of glucose in our bloodstream for cellular processes to work as intended. Delicate because 5gm of glucose spread across the entire circulatory system is optimal, while 7gm means you have diabetes. All down to that amazing organ, the liver.

When the body is not in need of the glucose available, the liver stores it as fat cells for later use. When the regular places to store fat, like subcutaneous fat, reach capacity, the glucose spills over into the blood, as excess trigycerides, into the liver leading to Non-Alcoholic Fatty Liver Disease (NAFLD), and into muscle tissue leading to insulin resistance. Fat also starts accumulating between the organs, called ‘visceral fat’ which is a source of inflammation.

The twist here is that fat—that is, subcutaneous fat, the layer of fat just beneath our skin—is actually the safest place to store excess energy.

Metabolic Syndrome is defined as having three or more of these five criteria: high blood pressure (>130/85) high triglycerides (>150 mg/dL) low HDL cholesterol (<40 mg/dL in men or <50 mg/dL in women) central adiposity (waist circumference >40 inches in men or >35 in women) elevated fasting glucose (>110 mg/dL)

Not everyone who is obese is metabolically unhealthy, and not everyone who is metabolically unhealthy is obese. So, visceral fat is much more of a concern than total body fat. Unfortunately, it takes a DEXA (dual-energy X-ray absorptiometry) scan to measure visceral fat, available only in a few places in India currently.

Preventing Heart Disease

If you’ve not been paying attention, this is the part where you start.

Three blind spots of Medicine 2.0 when it comes to dealing with atherosclerotic disease: first, an overly simplistic view of lipids that fails to understand the importance of total lipoprotein burden (apoB) and how much one needs to reduce it in order to truly reduce risk; second, a general lack of knowledge about other bad actors such as Lp(a); and third, a failure to fully grasp the lengthy time course of atherosclerotic disease, and the implications this carries if we seek true prevention.

Your “total cholesterol,” the first number that people offer up when we’re talking about heart disease, is only slightly more relevant to your cardiovascular risk than the color of your eyes.

Firstly, cholesterol is essential to life because it is used to produce some of the most important structures in the body, like cell membranes, hormones and bile acids for digesting food.

HDL / LDL (High / Low-Density Lipoprotein) refers to particles circulating in the blood and has to do with the amount of fat relative to the protein each one carries. LDLs carry more lipids, while HDLs carry more protein relative to fat and are therefore more dense. But, these particles frequently exchange cargo. The problems come from the nature of particles they are transported in.

These carriers are called apolipoprotein that provide structure, stability, and solubility to the particle. HDLs are wrapped in apolipoprotein A (apoA), while LDL is encased in apolipoprotein B (apoB). The distinction between apoA and apoB is the root cause of atherosclerosis or heart disease.

To gauge the true extent of your risk, we have to know how many of these apoB particles are circulating in your bloodstream. That number is much more relevant than the total quantity of cholesterol that these particles are carrying.

Significant lipoprotein burden or apoB, LDL oxidation or modification, and a high level of background inflammation. None of these is enough to guarantee that someone will develop heart disease, but all three are necessary to develop it

lipoprotein(a) – the little-known protein responsible for sudden cardiac arrest

Not to be confused with Apolipoprotein (apoA), Lp(a) is likely responsible for sudden, seemingly premature heart attacks. It is the most prevalent hereditary risk factor for heart disease and is still relatively unknown.

If you have a history of premature heart attacks in your family, you should definitely ask for an Lp(a) test.

Having only ever heard of HDL, LDL and Triglycerides with respect to heart health, everything in this section was brand new information to me. Turns out that getting checked for apoB and Lp(a) is convenient and not expensive. I was able to get the ones below from a neighbourhood diagnostic center, at a nominal price.

Accessible at most diagnostic test centres

Cancer: The runaway cell

Cancer cells are different from regular cells in two important ways: they don’t stop growing when they are supposed to and they have the ability to travel from one part of the body to a distant site they should not be.

In addition to being hard to detect early, cancer is a condition with mind-boggling complexity. The Cancer Genome Atlas found that “each tumour had more than one hundred different mutations, on average, and those mutations appeared to be random.”

They also have possess two hallmarks: cancer cells have an altered metabolism, consuming huge amounts of glucose, and they have the ability to evade the immune system, which normally hunts down damaged and dangerous cells.

Globally, about 12 to 13% of all cancer cases are thought to be attributable to obesity. Obesity itself is strongly associated with 13 different types of cancers. Type 2 diabetes also increases the risk of certain cancers, by as much as double in some cases

I suspect that the association between obesity, diabetes, and cancer is primarily driven by inflammation and growth factors such as insulin. Accumulation of visceral fat (and other fat outside of subcutaneous storage depots), helps promote inflammation, as dying fat cells secrete an array of inflammatory cytokines into the circulation. This chronic inflammation helps create an environment that could induce cells to become cancerous.

And so, getting our metabolic health in order is essential to our anticancer strategy.

The working hypothesis is that because cancer cells are metabolically greedy, they are more vulnerable than normal cells to a reduction in nutrients-or more likely, a reduction in insulin.

Chasing Memory: Alzheimer’s and Other Neurodegenerative Diseases

Alzheimer’s disease is perhaps the most difficult, most intractable of the Horsemen diseases. We have a much more limited understanding of how and why it begins, and how to slow or prevent it, than we do with atherosclerosis. Unlike with cancer, we currently have no way to treat it once symptoms begin.

The APOE genotype with the e4 variant is a risk-marker for future Alzheimer’s disease. But there are also centenarians with the genotype with no signs of dementia.

The plastic nature of our brains, meaning the brain’s ability to compensate for damage conceals early stages of neurodegeneration. Alzheimer’s disease in particular seems to be twice as prevalent in women than men.

Resisting cognitive decline is easier with more networks and subnetworks that come from education, experience, or by developing complex skills such as speaking a foreign language or playing a musical instrument.

Similarly, people with better movement patterns and a history of moving their bodies tend to resist the progression of Parkinson’s Disease when compared to sedentary people.

The single most powerful item in our preventive tool kit 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.

Sleep is also a very powerful tool against Alzheimer’s disease. Sleep is when our brain heals itself; while we are in deep sleep our brains are essentially “cleaning house,” sweeping away intracellular waste that can build up between our neurons. Sleep disruptions and poor sleep are potential drivers of increased risk of dementia.

The most powerful longevity drug


Even a little bit of daily activity is much better than nothing. Going from zero weekly exercise to just ninety minutes per week can reduce your risk of dying from all causes by 14 percent. It’s very hard to find a drug that can do that.

The two core components of health:

  • Respiratory fitness: How effective your lungs are at supplying oxygen to the rest of the body. Measured as VO2 Max
  • Muscle Mass: What percentage of your body is muscle. He emphasises the need to maintain muscle mass as protection against debilitating injuries that greatly take away from quality of life, especially as we age

The book goes into detail about the different kinds of training needed to support both those aspects of fitness. This is the part where reading the author’s regimen makes you feel like an immobile lump. But all the preceding background on what’s happening inside our bodies as we age should serve as the motivation to get started.

In a nutshell, languid walks in the park while catching up on phone calls might not count as exercise.

Nutrition: There is no best “diet”

You know those studies that get reported in newspapers about <insert random food / drink / ingredient> increases lifespan? They’re almost all the product of bad science. It’s simple, to know for sure that a specific diet or food is better than others, you’d need a study that identifies a test and a largely identical control group and follow them over several years while making sure one group ate that diet and the other absolutely did not. Instead, most such studies are based on small samples run over short periods of time, often with self-administered questionnaires relying on respondent memory.

Nutrition is far more nuanced than that. Wearing a CGM (Continuous Glucose Monitor) has taught me that the same food that causes a tremendous glucose spike in one person might cause barely a ripple in another.

The general principle is to avoid what is called the Standard American Diet (SAD).

The elements that constitute the SAD are almost as devastating to most people as tobacco when consumed in large quantities, as intended: added sugar, highly refined carbohydrates with low fiber content, processed oils, and other very densely caloric foods.

Sounds like a supermarket aisle in any Indian city with its rows of brightly coloured “foods”. Might as well be called SID (Sad Indian Diet).

Any diet that cuts out those ultra-processed foods will show benefits, irrespective of what the replacements are.

There are several tactics one can adopt to improve nutrition, from caloric restriction (overall reduction), dietary restriction (avoiding specific food groups) or time-restricted feeding (eating within shorter timeframes).

The key is to pick a strategy to which you can adhere but that also helps achieve your goals. This takes patience, some willpower, and a willingness to experiment.

Later sections go into the major food groups: Carbohydrates, Fat, Protein and Alcohol (as a separate category), their role in our body and what is the ideal mix.

He ends the chapter on nutrition with this:

Stop overthinking nutrition so much. Put the book down. Go outside and exercise.

There is another chapter on the importance of Sleep, which I now feel, doesn’t need as much emphasis as it once might have. And lastly on the importance of emotional health.

I will say this. I thought the book is a bit grim, about the way our bodies and minds inevitably deteriorate over time. And how everything we do in our daily lives will either speed up or slow down that process. But take a look around at any mall foodcourt, the options on offer and the long queues. That is hyperbolic discounting in action, the tendency to pick smaller, immediate rewards over larger, longer term rewards. And maybe the book strikes just the right note of urgency.

I’ll reiterate, nutrition and fitness are incredibly complex topics. The core principles stay consistent but what tactics works for one won’t necessarily work for someone else. So we need to resist dogma and have a researcher’s mindset when it comes to figuring out what’s right for us.

Read the book:

Further Reading:

Rapamycin: The unlucky history of the most powerful anti-aging drug [Big Think]