In January 2022, Altos Labs launched with $3 billion from Jeff Bezos and Yuri Milner to pursue cellular reprogramming. That single round was larger than the cumulative venture capital spent on senolytics in the previous decade. The bet: biological age can be wound back at the molecular level.
The evidence that it has happened in a human is zero.
The technologies called de-ageing fall into three buckets. Partial epigenetic resetting uses OSK factors to shift gene expression without erasing cell identity. Senolytics kill senescent cells that accumulate with age. Plasma dilution and related therapies remove or dilute aged blood components. All three have shown effects in mice. None has produced a peer-reviewed, replicated demonstration of rejuvenation in a person. This matters because the market for biological age tests is already large and largely unregulated. A consumer can pay a few hundred dollars for an epigenetic clock reading and then buy supplements or clinic visits on the strength of that number. The test and the therapy are sold as a pipeline. The science connecting them is not yet a pipeline.
The Three Technology Stacks and Who Is Building Them
Partial epigenetic resetting
Altos Labs is the best-funded player, focusing on Yamanaka factors (OSK) delivered transiently to avoid tumor risk. Dr. David Sinclair's lab at Harvard published a 2020 paper in Nature showing that partial resetting restored vision in mice by regenerating optic nerves. No human trial has started as of October 2023. The approach is preclinical.
Senolytics
Unity Biotechnology went public in May 2018 and saw its lead candidate UBX0101 fail a Phase 2 trial for osteoarthritis in August 2020. The company has pivoted to other indications. Other senolytic programs remain in early human studies. The mechanism is plausible: clearing senescent cells reduces inflammation in animal models. The translation to human joints failed.
Plasma dilution and related therapies
This category includes young blood transfusions, plasma exchange, and albumin dilution. The most prominent human data come from small studies of plasma exchange in older adults. No large randomized trial has reported positive findings. The approach is experimental and mostly pursued by smaller clinics outside mainstream regulatory oversight.
Regulatory Classification Determines What Is Possible
The US: ageing is not a disease
Whether an intervention is a drug, a biologic, a medical device, or an unregulated wellness product determines how it reaches patients and how much evidence is required. In the US, the FDA has not recognized ageing as a treatable indication. That means a company cannot file an Investigational New Drug application for ageing itself. It must pick a disease: osteoarthritis, frailty, macular degeneration.
Unity's UBX0101 was tested for osteoarthritis because that gave a clear endpoint and a regulatory path. The TAME trial, led by Dr. Nir Barzilai, received FDA clearance to test metformin for ageing-related outcomes but has struggled with funding because the indication is not a disease. The trial is designed to delay the onset of multiple age-related conditions, not to treat a single one, which makes it harder to monetize.
Europe and the WHO
In the EU and UK, the same logic applies. The World Health Organization included old age as a classification in the ICD-11, which took effect in January 2022, but that classification does not create a regulatory pathway. It is a coding change, not a license to market a drug.
The wellness loophole
Consumer tests face no such barrier. Epigenetic clocks are sold as wellness products, not medical devices. No FDA clearance is required. A test that claims to measure biological age can be marketed with no clinical validation of its link to any intervention.
Biological Age Clocks Are the Gateway, Not the Destination
The Horvath clock, first published by Steve Horvath in 2013, measures DNA methylation at specific CpG sites and correlates with chronological age. It is the most cited epigenetic clock and the basis for many commercial tests. The clock is a research tool that has been repackaged as a consumer product.
The problem is interpretive. A change in a clock score after an intervention does not prove rejuvenation. It proves that methylation patterns shifted. Whether that shift corresponds to a functional improvement in tissue, organ, or organism is an open question.
Several companies sell tests that report a biological age and then recommend supplements or lifestyle changes to lower it. The same companies sometimes sell those supplements.
The gap between a test result and a validated therapy is the distance from a Horvath paper to a failed Unity trial. That gap is where most of the revenue sits. Consumers pay for the test and for the product that promises to improve the score. The clinical evidence that the product actually reverses ageing is thin or absent.
Investment Flows Follow the Science, Then the Hype
The big bets
Altos Labs raised $3 billion in 2022, making it the largest single bet on reprogramming. Calico, Google's anti-ageing company, was founded in September 2013 with an initial commitment of up to $1.5 billion. These are strategic investments from billionaires who can afford a 10 to 20 year timeline.
The rest of the field
The rest of the sector operates on smaller rounds and shorter timelines. Unity's IPO in May 2018 raised about $125 million. The TAME trial has sought funding from foundations and philanthropists because no single drug company sees a clear path to revenue.
A cautionary tale
The Sirtris story is a caution: GlaxoSmithKline paid $720 million in 2008 for the resveratrol startup and shut it down in 2013 after disappointing findings. The price was set by GSK's board as a public acquisition; check GSK's 2008 annual report for the final terms.
The influencer track
Bryan Johnson's Blueprint protocol is a personal experiment, not a company, but it has drawn attention to the idea of quantified self-optimization. Johnson has published his biomarker data and his protocol online, but as of October 2023 the outcomes have not been peer-reviewed or published in a scientific journal. His influence on the sector is cultural, not scientific.
What Has Actually Worked in Humans
The track record
No intervention has produced a peer-reviewed, replicated demonstration of permanent biological age reversal in a human. The closest candidates are metformin, which has decades of safety data and observational evidence of reduced age-related disease, and the TAME trial, which aims to test it prospectively. TAME received FDA clearance but has not reported findings as of October 2023.
Landmark in mice, silence in people
Sinclair's 2020 Nature paper showed optic nerve regeneration in mice. That is a landmark in animal models. It is not a human outcome. Unity's UBX0101 failed a Phase 2 trial. Sirtris's resveratrol failed to show meaningful effects. The field has more failures than successes.
The real debate
The scientific debate is not about whether ageing can be slowed. Caloric restriction and exercise do that. The debate is about whether the biological clock can be turned back to a younger state and held there. That has not been shown in humans. The mainstream geroscience position, as reflected in FDA guidance and NIH funding priorities, is that ageing is a risk factor, not a disease, and that interventions should be tested against specific disease endpoints.
The Role of Billionaires and the Credibility Problem
Money and motive
Altos Labs' $3 billion from Bezos and Milner signals that serious money believes reprogramming will work. It also creates a credibility problem. When a sector is bankrolled by billionaires with a personal interest in extending their own lives, the incentive to overstate findings is high. The line between investment and vanity is blurred.
The self-experimenter
Bryan Johnson's Blueprint protocol is the extreme case: a personal experiment that has become a media story. Johnson's claims of reduced biological age are based on his own interpretation of his own data. The protocol has not been independently validated. It is not a clinical trial.
The long game
Calico, with its $1.5 billion from Google, has published some of the most rigorous preclinical work in the field but has not brought a candidate to market. Its timeline is long and its progress is incremental. That is probably the honest signal: real progress in ageing biology is slow, expensive, and measured in decades, not quarterly reports.
The sector will remain bifurcated. On one side, well-funded labs working on reprogramming and senolytics with no near-term product. On the other, a consumer market selling tests and supplements with little clinical evidence. The two sides are not connected by science yet. They are connected by marketing.
Key Facts
- Largest single investment: Altos Labs raised $3 billion in January 2022 from Jeff Bezos and Yuri Milner.
- First major corporate commitment: Calico, Google's anti-ageing research company, launched in September 2013 with up to $1.5 billion.
- Most cited epigenetic clock: Horvath's clock, published by Steve Horvath in 2013, measures DNA methylation to estimate biological age.
- Key animal result: Dr. David Sinclair's lab published optic nerve regeneration in mice using partial reprogramming in Nature, 2020.
- Failed clinical trial: Unity Biotechnology's senolytic UBX0101 failed a Phase 2 trial for osteoarthritis in August 2020.
- Acquisition and shutdown: Sirtris Pharmaceuticals was bought by GlaxoSmithKline for $720 million in 2008 and shut down in 2013.
- Regulatory milestone: The WHO added old age to ICD-11 in January 2022, but it does not create a drug approval pathway.
- TAME trial status: Received FDA clearance but has struggled with funding; no results reported as of October 2023.
Comparison of Major De-Ageing Approaches
| Approach | Mechanism | Leading Company | Stage | Human evidence |
|---|---|---|---|---|
| Partial epigenetic reprogramming | OSK factors reset gene expression | Altos Labs | Preclinical | None |
| Senolytics | Clear senescent cells | Unity Biotechnology | Phase 2 (failed) | None in Phase 2 |
| Plasma dilution | Remove or dilute aged blood components | Various small clinics | Experimental | No large positive trial |
| Metformin (repurposed) | AMPK activation, multiple mechanisms | TAME trial (Nir Barzilai) | Phase 3 (recruiting) | Observational only |
| Epigenetic clocks (tests) | DNA methylation measurement | Multiple consumer companies | Commercial | No validated link to therapy |
Frequently Asked Questions
Has anyone reversed their biological age in a clinically meaningful way?
No. As of October 2023, no peer-reviewed, replicated study has demonstrated permanent biological age reversal in a human. Some interventions show biomarker changes, but these have not been linked to functional rejuvenation.
Are consumer biological age tests regulated?
No. Epigenetic clocks sold directly to consumers are classified as wellness products, not medical devices. They do not require FDA clearance or clinical validation of their link to any intervention.
Can I get a de-ageing therapy from a clinic today?
Some clinics offer off-label therapies such as plasma exchange or senolytic supplements, but these are not approved by the FDA or equivalent regulators for the purpose of reversing ageing. The evidence supporting them is weak.
Does the FDA recognise ageing as a disease?
No. The FDA has not approved ageing as a treatable indication. Companies must test their interventions against specific disease endpoints such as osteoarthritis or frailty.
Why did Sirtris fail?
Resveratrol, the compound Sirtris developed, failed to show meaningful clinical effects. GlaxoSmithKline acquired the company for $720 million in 2008 and shut it down in 2013.
