“How to be 18 years old again for only $2 million a year:
middle-aged tech centimillionaire Bryan Johnson wants to have the brain, heart, lungs, liver, kidneys, tendons, teeth, skin, hair, bladder, penis, and rectum of an 18 year old – and his team of 30 doctors have a plan to help him get it. Led by physician Oliver Zolman, their plan to reverse the ageing process includes strict guidelines for Johnson’s diet (1,977 vegan calories a day), exercise (an hour a day, high-intensity three times a week) and sleep (at the same time every night, after two hours wearing glasses that block blue light). Each month, he also endures dozens of medical procedures, some quite extreme and painful, then measures their results with additional blood tests, MRIs, ultrasounds and colonoscopies.”
The Fountain Of Youth
How did you come to be interested in the Longevity space personally and professionally?
When I was in sixth form, I got a scholarship to study at a more academic school, which kick-started my interest in science. Before that, I was mainly hooked on business, especially after reading Losing My Virginity by Richard Branson. I started reading undergraduate chemistry, biology and physics textbooks – and took a particular interest in stem cells. I was fascinated by all the biology you can do with them: iPSCs (induced pluripotent stem cells), Yamanaka factors, and built-in transdifferentiation in some animals that age differently.
Around the time that I’d got my offer from Kings College, a friend of mine was doing a talk on a summer science internship in Israel. I applied and was interviewed by Andre Geim – the Ignobel prize winner that levitated frogs using magnets. Initially I was on the waitlist, but got the place after someone else dropped out.
In Israel I met a girl called Shahar at the Weizmann Institute, who invited me to a longevity conference back home. The guy running it was called Aubrey de Grey and after messaging him, he let me barter the ticket prices down to a more student-friendly rate. I was easily the youngest person in the room, which was full of super nerdy, veteran longevity scientists. What I realised was that there weren’t really any doctors there, and I felt like there was space for a physician to pull it all together and get these therapies out to people.
Ageing just felt like the most rational thing to focus on – it affects everyone and the tech involved would solve most other ICD-11 conditions at the same time.
Is there anything that makes your approach unique?
Firstly the volume – we have access to thousands upon thousands of biological ageing tests and therapies, as well as associated clinical guidelines. It’s as comprehensive as it gets, and I feel confident that even though it’s not necessarily mainstream – we have accumulated the best evidence of efficacy and safety that’s possible. The risks are always carefully calculated.
Are there any particular results you’d like to share?
I voluntarily spent hundreds of hours betting my father that I could calculate the age of his heart using echocardiography, without the regression equation knowing his chronological age. No machine learning or AI involved – just linear and non-linear regression. So far, we have been scarily accurate and can calculate chronological heart age perfectly just from functional and structural echocardiographic markers (I combine 20+ regression equations into the model).
It shows nothing has stopped echocardiographic heart ageing yet. We anticipate needing some advanced cardiac targeted measures – a lot of CDCs (cardiosphere derived cells), gene therapies, Yamanaka factors, ECM biostimulators, in-vivo bioprinting etc. Maybe even transplants.
One of the issues with the industry is that people want to solve ageing, but it’s not even being measured properly in most cases, and it’s embarrassing to see this on behalf of many clinicians in the space. I have the Zolman Biological Age Marker Criteria – 15 biostatistical criteria that I believe a good measure of biological ageing should meet. It’s not perfect but we do the best with what we have. When it comes to the brain especially, it’s a lot more limited in terms of what we know and can achieve.
Are there any benefits that are not encompassed by a reductionist science? How do you balance quantitative and qualitative metrics?
Everything in science is reductionist to varying degrees, for example quantifying mental health and happiness states using questionnaires. The guidelines we have for each test come from the clinical literature with references, then we get people to peer review it and are trained to use it.
We have MRIs, ultrasounds, surface imaging, photogrammetry, OCT, multi-spectral imaging, 100+ medical devices (physical and virtual, e.g. VO2 max and nocturnal penile tumescence vs Addenbrooke’s cognitive assessment and CANTAB cognitive scoring); then biosamples: biofluids, gases and solids; including proteins, mRNA, metabolomics, lipids, sugars, small molecules, methylation, genetics, full stack – the list goes on.
Explain how you work with some of the root causes
We can’t biopsy every organ so we mostly work with indirect instead of direct causes – you have to use surrogate markers, or you can measure things like bio-fluid samples. MRI, ultrasound, photographs, photogrammetry, autofluorescence imaging, multispectral imaging, optical coherence tomography, fNIRS etc are all imaging modalities used, as well as 100+ different medical devices (physical and virtual). Just reverse everything safely and then you hit the root causes without even measuring them, all that matters is measuring all supposedly clinically relevant changes with age.
How do you adopt an often experimental and personalised approach to what you do, while still seeking to leverage relevant evidence from the existing literature base?
Every test and therapy has a clinical guideline based on systematic reviews. We start at the top of the pyramid of evidence and work down – Pubmed clinical queries, high ROC RCT search terms, meta analyses, Google scholar, Chinese databases etc. I go down to good mouse or monkey studies but stop there. No worm studies.
First I look for the biggest clinical outcome benefits that are supported by my ageing biomarker models. For example LV E/A decreases with age in the heart, so I look for evidence of therapies that raise E/A in relevant populations, then build clinical guidelines around that. Our whole evidence-based medicine method is open source on our website: longevity.school/methodology
How do you formulate the contents of your Wine Span supplement to be bioavailable?
It works without alcohol or water and is shown to be clinically active in isolated form in multiple RCTs
What approaches do you take to mental health and why?
I use my mental health clinical guideline in longevity level 2 – it summarises all the RCTs on interventions, there’s a lot more than in the NICE guidelines and USA equivalents. For example 10k lux light therapy, or 810nm NIR light therapy, with some studies showing SSRIs stack well on top of this. It would be good to know more about the NICE selection criteria and why they don’t include evidence such as this.
How was the business fundraising process for you?
We didn’t need one thankfully!
What unforeseen challenges and opportunities have arisen?
It’s all been going pretty smoothly.
What’s brought the most traction and momentum for you? And what hasn’t worked so well?
Pubmed and the medical journal system is a wonderful invention. However there is definitely a knowledge gap, and too many studies for governments, clinicians or people to implement – so that’s where all the benefit is.
What’s the smallest change that’s given the biggest return?
To reduce calories by 25% without side effects probably.
Have any candidates used or benefitted from the products in ways you didn’t expect?
When you run the bio-stats on it, there’s a lot of placebo-related results. A lot of the time you think something is happening, but then it stops having an effect after a while, or the results don’t add up – so it’s the expectation that’s created an effect.
We also repurposed a women’s pelvic health pad for men’s pelvic health, which has had interesting results so far… We may be seeing an increase in pelvic floor strength in men, as well as an increase in nocturnal penile tumescence total time per night averaged across 30 days plus.
This penile organ age marker drops 50% or so from age 20 to 80 (e.g. 4 hours to 2 hours per night) and can lead to ED and low sexual satisfaction scores. So it’s an important one, and this therapy is non-invasive. But we need to test it on more people and for longer; RCT (randomised controlled trials that aren’t majorly flawed on GRADE or Cochrane analysis are the gold standard).
What motivates you?
Endless Pubmed novelty, vanity, and guilt.
What does it mean to live ‘well’?
Good time all the time (Chad Smith 1993)
Do you have mentors or people you ask for advice?
Yes – confidential!
If you did not have your own company, what would you be doing?
Starting my own company or getting fired from someone else’s.
There’s no other way for me. Gary Vee is one of my inspirations.
How has what you do changed you as a person?
I don’t feel I’ve changed a huge amount throughout my life.
What does spirituality mean to you?
I don’t know!
If time and money were no object – what would be on your to-do and to-see list?
I live for what I do – so it would be to spend more time financing a huge amount of research!