Age Later by Nir Barzilai
Name: Age Later
Author(s): Barzilai, Nir
Published: 2020
The Core Problem: How can we delay aging and extend our healthspan, not just our lifespan?
The Bottom Line
- What it is: Age Later explores the science of why we age and what we can learn from centenarians who “age later”.
- Why it matters: For growth-oriented professionals, a longer healthspan means more years of peak contribution, impact, and personal fulfilment.
- What you’ll get: Practical insights on lifestyle, emerging therapies, and mindset shifts to help you age slower and live healthier for longer.
Time Commitment:
Disclaimer: This content is intended for educational, commentary, and review purposes only. All opinions expressed are my own and are not affiliated with the author or publisher of the book. Any copyrighted material, including quoted excerpts, is used under the principles of fair use for criticism and analysis. For further information or to support the author, please refer to the links mentioned at the beginning of this page.
The Strategist’s Briefing
Ageing is a disease: If you think about it, for us to grow weaker as we grow older does not really make sense – it is something that we have just assumed as an immutable fact about life.
Till about our 25s or even 30s, things are on an upward trend, our bodies are generally getting faster, stronger, better at living.
And then things start going slightly downhill (we may not even notice), and then they really start going noticeably downhill when we hit our 50s. Why?
Why are our bodies programmed to have a self-destruct button? Why are we born with this time bomb inside us?
Nir Barzilai, a pioneering longevity researcher and director of the Institute for Aging Research at the Albert Einstein College of Medicine, is here to tell us why. His studies on centenarians reveal genetic and lifestyle factors that allow some people to live long, vibrant lives.
He writes: We have a hundred to thousandfold greater chance of dying from aging than of dying from other risks like obesity or high cholesterol.
Let that sink in. Aging is so powerful that a dedicated 80-year-old who does all their exercises, takes all meds and supplements, sleeps well, maintains hygiene, has good social connection and life purpose is still more likely to be dead the following year than an obese twenty-something who does nothing.
Peter Attia has written: 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.
That, is actually a pretty good answer, according to me.
Anyway, what this book is – is basically a story about the author’s experience with centenarians, people who live to 100 years of age and often beyond and are thus able to “age later”, along with his experience with various stakeholders involved in the medical, geroscience and longevity field as he set up studies, experiments and companies to find out how this ageing thing works.
Let’s see if there is something that mere mortals like me can take home.
Core Frameworks Deconstructed
Citation: All text highlighted in yellow in this section is cited from – Barzilai, Nir ; Robino, Toni. Age Later: Health Span, Life Span, and the New Science of Longevity. Kindle Edition.
Super agers
Centenarian – Someone who is a 100 years old or more.
There are some people who “age later”, You know them by the word “centenarian”. Not only do they live longer, they’re also healthy for most of those years, and when they do die it’s fairly quick (squaring the mortality curve).
It’s not that super agers don’t get the main chronic diseases (ASCVD, disbetes, cancer, neurodegenerative disease), they just get them later, way later in life, like decades later.
The reason they are able to do this is because of unique genetic makeup (there is no “one” perfect genetic configuration) that makes each individual centenarian live long.
Also, longevity runs in families.
Generally, centenarians: Have high levels of good cholesterol (HDL), as well as larger (in size) HDL and LDL particles, have unusually low levels of IGF-1, have unusually high levels of some mitochrondrial-derived peptides (MDPs)
It’s not that centenarians have perfect genomes or that they lead super healthy lives (some of them do), but rather that they are protected from the consequences of ageing by parts of their own DNA (more specifically, variations/mutations in certain genes) – Yep, by virtue of being alive all of us have won the genetic lottery, but these folks seems to have won more.
The book goes into detail about what we know of these mutations and their effects, such as loss-of-function mutation in the CETP gene (increases HDL) and the APOC3 gene (increases HDL, lowers triglycerides), deletion of exon d3GHR (lowers IGF-1 production), variation in FOXO3 (improves metabolism, cardiovascular health).
Concept 1: [Name of the Core Concept]
Principle: Centenarians often possess unique genetic variations that delay the onset of age-related diseases.
Application: While you can’t pick your genes, you can emulate certain protective lifestyle factors (e.g., cholesterol management, inflammation reduction).
Strategist’s Note: Genetics load the gun, but environment and behaviour pull the trigger. Your focus should be on the 75–80% of aging determined by lifestyle, not the 20–25% by genetics.
Ageing for the rest of us
We age because, well, there are a few reasons (there may be more):
Genomic instability: DNA in our cells develops random mutations, these mutations are less likely to get fixed the older we are, leading to impaired cellular functioning that at large enough scale starts to impact organs. Telomere damage/shortening may be one of the reasons for these mutations.
Epigenetic damage: As we age, our cells lose information (become less adept at reading DNA) because epigenetic mechanisms scramble the information on the DNA, which leads to disease a general ability to function. Factors like:
- DNA methylation (process that activates or deactivates genes).
- Histones (package DNA into units and have role in gene regulation).
- MiRNA (micro RNA) can silence other RNA thus prevent gene expression.
Mitochondrial dysfunction: As we age, our mitochondria suffer free radical damage and accumulate damage in their own DNA, which impairs their ability to produce ATP. Mitochondrial dysfunction is associated with a bunch of serious health issues.
Metabolic dysfunction: Our bodies become less efficient at converting food into energy.
Cell senescence: Cells that refuse to die naturally (a process known as apoptosis) and instead linger around releasing inflammatory cytokines, which then start impacting the rest of the body negatively.
Challenges in Proteostasis: The body becomes less efficient at clearing out misassembled proteins.
Antagonistic pleiotropy theory: Biological resources we need for reproduction when we are young may end up hurting us when we are old (like growth hormone and IGF-1).
Inflammation: If inflammation is chronic then it contributes to ageing.
Immune dysfunction: Bodies get less efficient at fighting disease.
Concept 2: Hallmarks of Ageing
Principle: Aging is driven by multiple interconnected processes: genomic instability, epigenetic changes, cellular senescence, mitochondrial dysfunction, and more.
Application: Adopt interventions that systematically target these hallmarks: regular exercise, caloric moderation, stress reduction, and mental engagement.
Strategist’s Note: Treat your body like a complex system — maintain it proactively rather than fixing it reactively. Think systems maintenance, not just symptom suppression.
Biological vs chronological clock
Chronological age is your age measured since the time you were born, simple.
Biological age, on the other hand, is supposed to be the “actual age” of your body basis what it can do and how well it works.
The point is: you want to generally have a younger biological age.
Broad consensus is still being formed on biomarker(s) of ageing that decisively reveal a person’s biological age.
DNA methylation seems to be a leading candidate for predicting biological age.
BTW even different organs inside a person can have different biological ages.
This image from Wikipedia that explains how methylation alters gene expression:
How to slow your biological clock
Exercise your body and brain: Exercising, across any book I have read till date, is universal advice.
Our bodies were built to move, so we should move them. Strength training, aerobic exercise and training for stability. Stay mentally sharp by learning new skills as you grow older.
Getting the right nutrition, not being over nourished: (this is a complex and often culturally intertwined topic, but generally) Eating in moderation, practicing some form of regular/daily (and occasionally longer) caloric restriction (esp. as we cross 30 years of age).
Getting the right macros (not too many carbs, but a good amount of fat and fibre).
Not being too lean (or course, not being fat either), hydrating well.
Supplement intelligently: Try not to experiment with too many nutraceuticals (depending on the country where you live, they may or may not be as strictly regulated as pharmaceutical drugs are), and take only that which you know you are deficient in.
If you are young then you may not deficient in anything and able to effectively absorb everything from your food, as you get older you may want to get checked for the following: vitamin B12, vitamin D and calcium.
Get tested: Important to figure out what is going on in your body, so get tested for the usual markers depending on your age (like HbA1C, CRP, HDL/LDL etc.)
Sleep well: Get your 8 hours of sleep, design the right environment and routine around your sleep.
Have purpose: If you live for something bigger than yourself then it is likely that you will live a happier and healthier life.
Be positive: Be easy-going, laugh often and optimistic. Don’t bottle up your emotions too much.
Try to have meaningful social connections. Life usually finds ways to challenge us, and having an overly paranoid, obsessive or pessimistic attitude is like adding fuel to the fire.
Discover your “Massively Transformative Purpose”
Concept 3: Lifestyle as Longevity Therapy
Principle: Physical activity, nutrition, sleep, social connections, and mindset are your primary levers for slowing biological aging.
Application:
- Move regularly (strength, cardio, stability).
- Eat moderately, emphasise healthy fats and fibre, and avoid excess carbs.
- Sleep deeply and consistently.
- Maintain a sense of purpose and positive social interactions.
Strategist’s Note: The fundamentals remain undefeated. Before exploring cutting-edge interventions, master these foundational behaviors.
Preventing a looming world crisis?
The world is living longer but it is not living healthier, and this means more older people get added to the world’s population each year.
They need to be taken care of and may not be able to contribute to society and economy like they once were, and importantly they live the last years of life in pain and disease – a fate no one wants.
This is unfortunate because older individuals generally have a wealth of experience and wisdom gained over a lifetime of making mistakes and learning what works – something that can be immensely valuable for younger generations.
The world’s health adjusted life expectancy (HALE) trails its life expectancy.
For example, in my home country of India, one can be reasonably expected to live 70-72 years, however, its HALE is between 50-59.9 years, which means that Indians are getting shortchanged a full decade of healthy living.
This is a key reason why longevity/healthspan R&D is crucial – The world is only going to live longer in the coming decades.
A pill for ageing?
When writing about the subject of health and longevity, I try not to discuss specific drugs or medicines, but I am making an exception for Metformin, which over the last decade has become a popular and promising “longevity” medicine.
Metformin: Indeed, the author thinks Metformin has great promise and talks at length about his plans to test it in his Targeting Ageing with Metformin (TAME) study. He also mentions that he takes Metformin.
Metformin is not new: it is an FDA-approved drug used successfully to treat diabetes for more than 60 years now. Apart from being effective in managing diabetes, it has also been efficacious in ASCVD and cancer.
However, the real reason metformin is so important is that if TAME is successful, it may be the first drug that will be marketed as one that targets ageing. This is nothing short of revolutionary and has significant scientific, economic and cultural consequences. And future generations of drugs that are developed as a result may be even better at “fixing” ageing.
Concept 4: Pharmacological Frontiers
Principle: Drugs like Metformin show promise in delaying aging-related decline and extending healthspan.
Application: While still experimental for aging, Metformin is safe under medical supervision and may become the first FDA-approved “anti-aging” drug.
Strategist’s Note: Stay updated but cautious. Early adoption can provide an edge, but always balance innovation with evidence and medical guidance.
In the concluding chapter of the book Barzilai talks about the more cutting-edge research and development that seek to stop and possibly reverse ageing. He talks about omics, personalised medicine, early detection, reversing cellular age, generic engineering and other pioneering explorations. He is hopeful that the drugs and other interventions that result from this research will keep most people healthy for additional decades and “… the most common side effect will be living to one hundred and beyond“.
High-Signal Quotations
Citation: All text in the following section is cited from – Barzilai, Nir ; Robino, Toni. Age Later: Health Span, Life Span, and the New Science of Longevity. Kindle Edition.
- Aging transforms us, remakes us, breaks us, destroys us. But why?
- By the mid – 1900s, human life span increased until the average reached eighty years, which is where we are now. But we start accumulating diseases after the age of sixty, and many people are being treated for three different diseases or chronic conditions by the age of seventy – five. So regarding the future of humanity and quality of life, it’s clear that finding a way to prevent or delay the onset of age – related illnesses is one of the most important mysteries we can solve.
- aging poses a dramatic increase in our risk of having every chronic disease.
- We experience old age and illness as one and the same thing, whether it’s diabetes or Alzheimer’s, Parkinson’s or cancer, but at seventy, the SuperAgers have twenty to thirty more mostly disease – free years ahead of them.
- That said, it’s important to clarify that centenarians’ bodies are not young. Many of them have some limitations like poor eyesight or hearing, some have less mobility than others, and arthritis is common. But the major diseases are delayed, and at the age of their retirement, many of them were not seeing a doctor and had no medical expenses.
- Demographers estimate that for most people , genetics are responsible for about 20 – 25 percent of aging and the environment is responsible for the rest. But the statistics are vastly different for centenarians, whose genes are about 75 – 80 percent responsible for how they age and the environment accounts for only about 20 percent.
- Evolution prioritizes reproduction, so that may be why the aging process picks up speed after reproduction.
- … rapid aging is the price paid to achieve better reproduction.
- Abdominal obesity — think older people who are thin but have big bellies — is the marker for the onset of diseases.
- … your body weight that has the biggest effect on your blood levels of cholesterol.
- “The important thing is to keep the brain going, you see”
- Morgan Levine, a pathologist at Yale; and a team of others have created what they call a “clock” that can predict the chronological age with just a few hundred methylation sites. This clock is a much better predictor than biological age , and there are companies already offering tests that use this innovation .
- I can tell you with certainty that growth hormones do not grow your life span.
- People who say that taking growth hormones makes them feel great are predominantly experiencing a placebo effect.
- Never put off your dreams.
- It really doesn’t matter what disease you have to begin with; your chances of getting any of the other diseases is the same because aging drives them all.
- Although functional decline is often caused by the burden of multiple diseases, in many other cases, the decline occurs without the presence of disease , suggesting that it’s simply a result of the aging process.
- For the first time ever, there are more people on earth who are older than sixty – five than people who are younger than five.
- Nobody wants to live to be one hundred if they are going to be sick for the last forty years.
- … when I ask older people what’s on their wish list, at the very top is getting a job … they want to be involved and contribute in whatever way they can.
- So to be clear, while there are scientists exploring immortality — and who can say whether they can achieve this goal or whether they should?
- Our maximum potential life span as a species is thought to be about 115 years, but many people die before the age of 80 after suffering from an average of three diseases. So we have 35 extra years that we can realize.
- Hands down, the most important intervention we have for aging is physical exercise, which has positive benefits for males and females at every stage of life.
- … what’s good for the heart often proves to be good for the brain, too.
- … older people’s brains become biologically wiser.
- … children who are in elementary school now will live long enough to meet their great – great – grandchildren.
- Based on the existing evidence, it appears that we’re meant to be physically active throughout our lives, but at some point between ages sixty and eighty, we start to lose energy and muscle strength as the biology of aging affects our whole bodies. Cardiovascular ability also declines with age, so strength training and cardiovascular exercises are particularly important as we get older. The key is to try a wide variety of activities and exercises that increase strength and bolster your cardiovascular system and to stick with the ones you like most.
- “If you have a reasonable life standard, if you are not in danger that you are going to lose it, and if you are not a dreamer, sit on your behind where you are. Don’t move. It’s not easy.”
- While muscle mass loss is a concern, losing strength is a more significant problem.
- We start losing muscle mass at about the same age that we see an increase in type 2 diabetes. Muscle is our most important organ for maintaining our sensitivity to insulin, because muscle stores most of the body’s sugar as glycogen.
- … paying attention to how much you eat and choosing to eat just a little less at each meal can make a big difference.
- … safe to assume that a diet that’s 65 percent carbohydrates or more is not beneficial.
- … lowest mortality rates are associated with people who probably have some extra subcutaneous fat, and this applies to men and women of all ages.
- Cold-pressed extra-virgin olive oil contains about thirty types of polyphenols that reduce inflammation and target the hallmarks of aging, particularly in the cardiovascular system and the brain. It also has lower acidity and tastes better than less healthy olive oils.
- Another way we can increase our chances for longer health spans and life spans is by taking steps to offset genetic mechanisms with lifestyle choices and — when they become available — new drugs that will be designed to specifically target those mechanisms
The Takeaways
It’s a good book, an honest book, a hopeful book.
Yes, it requires the reader to have a certain interest in the subject but it reads well, almost like a story and it seemed to me that the author was writing from the heart as he takes us through the book.
All well and good, but what do I care if some old folks have variations in their genes that allow them to live to a hundred?
There were large parts of the book where I did not get any particular insight for this note.
Only when I got to chapter 8 is where the more practical advice for starts and it does not last for very long or is very specific.
So this is not an instruction manual on how to live longer, it’s an observation log of those who actually do end up living longer.
Side note, I think its a little amusing to be alive at a time where we might be at the cusp of breakthrough, affordable, widespread and (hopefully) democratic increase in our lifespans and healthspans right at the time we are at also risk of making the world less habitable through climate change.
Your 3-Point Action Plan
- Design a longevity protocol: Integrate daily exercise, dietary moderation, high-quality sleep, and regular medical tests into your life immediately.
- Monitor your biological age: Begin tracking biomarkers to get a true read on your physiological progress rather than guessing based on years lived.
- Engage with purpose: Find and commit to a cause bigger than yourself — it fuels mental resilience and supports longer, healthier living.
The learn more about how you can cheat ageing – Read the Field Note on Lifespan by David Sinclair.
–
Aviral Prakash
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