Level 2 · BiohackingBiohacking UpgradesMetformin, growth hormone and the case that a drug can target ageing itself.
Level 1 · BasicsLongevity BasicsWhat he actually wished for us: exercise, nutrition, sleep, social connection — and a purpose.
Live Beyond · A Great Mind on the Quest
Nir Barzilai
Physician-scientist, Albert Einstein College of Medicine · centenarian genetics & metformin “You’re looking at your grandparents. That’s where you’re going” · Singapore
Of his centenarians have something unusual in growth hormone
“By November”
His answer on timing — if you don’t ask the year
Who is Nir Barzilai
Not everything good for you young is good for you old
Nir Barzilai is a physician-scientist who built his career on a simple, awkward question: why do some people reach a hundred in good health while their contemporaries do not? His work on the genetics of exceptional longevity put centenarians at the centre of ageing research, and he has spent years arguing that ageing itself can be targeted by a drug — with metformin as the test case.
The most practically useful thing he told us is about timing. He is often quoted as saying metformin is for after fifty, and there are two reasons. The first is evidence: seven decades of research recruited people over fifty, with an average age nearer sixty-five. The second is mechanism — metformin lowers growth hormone, and in some men lowers testosterone. When you are young and still building, that is a trade you do not want.
He puts it as a rule worth carrying: “Not everything that’s good for you when you’re young is good for you when you’re old, and the other way around.” He is equally frank about the downside — three to six per cent of people get diarrhoea that does not resolve, because they lack the transporter that carries metformin into cells.
On the limits of lifespan he is careful rather than pessimistic. There is a ceiling, and the curve is starting to bend against us — but he does not believe it is permanent. And on AI he is refreshingly unimpressed by hype: he will ask ChatGPT about his own research and get a good story back, but ask it what to do next and it has nothing. “They still need me. The day they don’t need me, I’m out of here.”
He was interviewed at NUS in Singapore alongside Andrea Maier, and the two of them turn up in each other’s answers — including a small disagreement about whether the right verb is optimise or maximise. He concedes she is probably right.
We met Nir at the National University of Singapore, where he was appearing alongside Andrea Maier. Two conversations came out of that visit — a joint one with Andrea, and this one. It ranges from artificial intelligence to metformin side effects, and finishes somewhere neither of us expected: on purpose, and on Aleksander’s face during the interview.
NUS, Singapore
February 2024
Interviewed alongside Andrea Maier.
Centenarians
Decades of work
The genetics of people who reach a hundred in good health.
Metformin
The test case
An old, cheap drug proposed as a way to target ageing itself.
“Seventeen, eighteen year olds look at their grandparents and say: what happened to them? That’s where you’re going. And you get there faster than you think.”
— Nir Barzilai, Singapore
On the quest
In Singapore
NUS, Singapore, February 2024. Nir was in Singapore alongside Andrea Maier — the two of them appear in each other’s answers.
In his words
“They still need me”
“If you ask me when it will happen, I’ll tell you: by November. As long as you don’t ask me the year, I’ll be right.”
Nir Barzilai · Singapore, February 2024
Not everything that’s good for you when you’re young is good for you when you’re old.
Nir Barzilai
I’m disappointed that it takes longer. It always takes longer than I think.
Nir Barzilai
Every medicine we’ll talk about has trade-offs.
Nir Barzilai
The bigger question is always a purpose in life. Evolutionarily this is not up to us — we have to invent it.
Nir Barzilai
In his own words
Straight from the interview
From the conversation in Singapore — on artificial intelligence, on when a drug is right for you, and on what he thinks a teenager should see when they look at their grandparents.
Why after fifty
Two reasons, and both are worth knowing. The evidence base was built on people over fifty — average age nearer sixty-five. And the mechanism cuts both ways: metformin lowers growth hormone, which is what you want when the body is breaking down and precisely what you do not want while it is still building.
“It doesn’t make sense to invest in growth when you’re starting to break down.”
Singapore · from the interview
On artificial intelligence
He uses it, and he is unromantic about it. It writes a good summary of his own research; ask it what experiment to run next and it stops. His other complaint is that big data keeps rediscovering the obvious — twenty years of records on three million people to establish that obesity raises diabetes risk.
“I didn’t need AI for twenty years to know that. I’ve known it for fifty.”
Singapore · from the interview
Peter Pan
His long-range picture is the most vivid image anyone gave us. In fifty years, he thinks, a seventeen- or twenty-year-old will go to the doctor and receive a treatment that erases their ageing — repeated every few months or years. They will not grow up.
LinkedIn, X and institutional page still to be confirmed — I have not verified an affiliation for him, and per our rule I would rather leave it off than take one from a 2024 transcript.
From the conversation
Nir Barzilai, in his words
Video interview
The video interview is coming. Recorded interviews go live after the launch of the film & series Live Beyond.
From the conversation at the National University of Singapore, February 2024. Lightly edited for readability. Nir was in Singapore alongside Andrea Maier, who has her own page.
On artificial intelligence
Nir Barzilai“When I go to ChatGPT and ask about my research, they’ll give me a good story. But if I say, okay, so what do I do next? They don’t know. They still need me. The day they don’t need me, I’m out of here.”
Nir Barzilai“For AI you need to ask the right question, and not everybody asks the right question. There’s data on twenty years of electronic medical records of three million people. And they discovered that obesity is a risk for diabetes. I didn’t need AI for twenty years to know that — I’ve known it for fifty.”
On working across disciplines
Nir Barzilai“I remember the first time I used computational tools. I sat with these AI people and said, we have to discover this thing. We talked, and we both thought we knew what we were saying. We agreed each of us would write the specific aim for the grant. We exchanged them the day before — and each of us thought the other was a total idiot, because we hadn’t understood each other at all.”
His message to Aleksander’s generation
Nir Barzilai“Seventeen, eighteen year olds look at their grandparents and say: what happened to them? Where did they come from? I think young people have to know that when they look at their grandparents, that’s where they’re going. You get there, and you get there faster than you think. And we can do something about it. I already look different from my father and grandfather. But if they’re not part of this revolution, it’s not going to work.”
Nir Barzilai“In fifty years, I think a twenty-year-old or a seventeen-year-old will come to the doctor and get some treatment that will erase their ageing. And they’ll repeat it every few months or every few years. They’ll be Peter Pan. They’ll never grow up.”
On the ceiling
Nir Barzilai“I believe that’s not going to be our limit. I think the limit is more to explain to people that it’s not going to be linear now. Before we solve the physical property — we do age, no matter what we do — life is extended and extended, and now there’s a roof. That means we’re going to start bending, and it’s going to be harder and harder to get there.”
On predictions
Marek Piotrowski“Brian Kennedy said longevity scientists should talk more with futurists, because scientists tend to be cautious about how fast the limits will move.”
Nir Barzilai“I find it the opposite. I cannot tell you how many times they’ve asked me what I think will happen in the next five or ten years — and I was much faster than it happened. I’m disappointed that it takes longer. It always takes longer than I think. It’s hard to make predictions, in particular about the future.”
On metformin, and who it is not for
Nir Barzilai“The research that’s been done for seven decades always recruited people over the age of fifty — in fact the average age was sixty, sixty-five, sometimes seventy. So we have the data in older people. One of the things metformin does is lower growth hormone, which is very important for ageing. In our centenarians, sixty per cent of them have some problem with growth hormones.”
Nir Barzilai“You need growth when you’re young. You need to be strong, you need to reproduce. When you start breaking down, it doesn’t make sense to invest in growth. Metformin lowers growth hormone — that’s not good when you’re young. In some males it also decreases testosterone. Not everything that’s good for you when you’re young is good for you when you’re old, and the other way around.”
Nir Barzilai“Metformin is also not tolerated by everyone. Three to six per cent of people get diarrhoea that doesn’t go away, because they don’t have the transporter that takes metformin into the cells. Every medicine we’ll talk about has trade-offs. For people who can tolerate it, it’s going to have an effect.”
His wish for the quest
Nir Barzilai“For you guys — exercise, nutrition, sleep and social connectivity is going to take you a long way, and that’s what you’re forcing yourselves to do. Your son is interested in this conversation. He has this little smile, and he agrees with me or he doesn’t agree with me.”
Nir Barzilai“I call it maximise; optimise is Andrea’s word. She’s probably right, because maximise means you always have to do more — and maybe you shouldn’t. The bigger question is always a purpose in life. Evolutionarily this is not up to us, we have to invent it — and it’s good to invent it, because it makes our life meaningful. And you have a purpose. Look at the trip you’re taking. It’s just wonderful.”
More passages from the full interview will be published here.
Continue the quest
More minds on the quest
Nir Barzilai sits in Biohacking Upgrades (pharma) with a real claim on Longevity Basics — asked what he wished for us, he answered exercise, nutrition, sleep and connection. Read him next to Andrea Maier.
