The four-axis ranking
We rank humanity’s most important problems on four quantifiable dimensions — quantity of humans affected, severity per capita, current solution quality, and addressable market size — and package each as a proposal in the spirit of Musk’s Hyperloop Alpha. This document is the proposal for longevity & aging. Every number below is sourced and tagged with confidence. Every ranking is a conjecture, open to refutation.
Quantity · humans affected
8.1B
highSeverity · WTP / wealth
25%
medCurrent solutions
2.0 / 10
lowMarket size · TAM
$4.0T
medWhat we are trying to solve
Aging underlies cardiovascular disease, cancer, neurodegeneration, and frailty. Every human alive is affected. The hallmarks-of-aging framework (López-Otín et al.) gives discrete targets: senescent cell clearance, epigenetic reprogramming, stem cell exhaustion. Partial cellular reprogramming (Altos, Retro, NewLimit) and geroprotective drugs (rapamycin, metformin class) are in early trials. Utility delta is enormous: current median healthspan ~75 years, theoretical ceiling unknown and likely much higher.
The gap between the world and the world that is physically possible
Today: Healthspan declines starting ~age 50. Aging treated as inevitable rather than as a disease. ~100M humans living with frailty-driven decline.
Current solution quality is rated 2.0 / 10 (low confidence) — meaning there is substantial unclaimed ground between what exists and what is possible. estimated — rapamycin, senolytics promising in mice; no FDA-approved life-extension intervention yet.
Who is already working on this
8 entities are currently working on this problem across public markets, private companies, and research orgs. Each is evidence the market is real; none has obviously solved it.
Recursion Pharmaceuticals
public · USAAI-driven drug discovery. Industrializes biology through automated phenotypic screening at scale.
$2.4B
Colossal Biosciences
private · USADe-extinction and genetic engineering. Biosecurity adjacency via rapid genome editing and cold-chain logistics.
$10.2B
Altos Labs
private · USACellular rejuvenation via partial reprogramming. $3B at founding with Shinya Yamanaka on scientific board.
$3.0B
Isomorphic Labs
private · UKAlphabet-spinoff applying AlphaFold-class ML to drug design. Deals with Novartis and Eli Lilly.
undisclosed
Calico Life Sciences
private · USAAlphabet company for aging biology. Research partnership with AbbVie; long-horizon mandate rare in pharma.
undisclosed
Retro Biosciences
private · USACellular reprogramming, autophagy, and plasma-exchange therapeutics. Seed-funded by Sam Altman at $180M.
undisclosed
NewLimit
private · USAPartial reprogramming for aging, started by Blake Byers, Jacob Kimmel, and Brian Armstrong.
undisclosed
Loyal
private · USAFDA-track longevity drug for dogs. First-of-its-kind lifespan-extension regulatory pathway.
undisclosed
If we solve this, here is the world we get
After · 30 years
Healthspan extended by 20+ years. Aging recognized as a treatable condition with FDA-approved interventions. 100→120-year healthy lifespan common in cohorts born after 2030.
Requests for startups · 2 concrete companies to build
Aging as an FDA-recognized indication
You cannot run a trial for a disease the regulator does not recognize. Build the company that runs the TAME-class trial and operationalizes aging biomarkers as approvable endpoints.
- why now
- Biomarker science (epigenetic and proteomic clocks) matured enough to be candidate endpoints; the regulatory path is the remaining frontier.
- shape
- A clinical-stage company designing and running the pivotal trial plus the regulatory-science work to make "aging" a legitimate, reimbursable indication.
- success
- Aging is a recognized indication with at least one approved intervention and validated endpoints.
The healthspan diagnostic
Medicine measures disease, not the slope of decline. You cannot manage what you do not measure. Build the longitudinal aging-clock and intervention-tracking company.
- why now
- Multi-omic aging clocks became reproducible enough to track individual trajectories over time.
- shape
- A consumer + clinical diagnostic that measures biological aging longitudinally and quantifies whether an intervention is bending the curve.
- success
- Individuals and trials can see, in months, whether an intervention slows aging.
full rubric + framing on the Requests for Startups page.
What the market can pay
The world is already paying $4.0T per year against this problem (global healthcare spend for ages 65+ (OECD Health Statistics); standalone longevity-tech market projected $44B → $600B by 2035; med confidence).
A successful solution does not need to capture more — it needs to redirect a meaningful slice of existing spend, plus the latent willingness-to-pay implied by the severity score above. The cost ceiling for a real solution is bounded by this number; everything cheaper is dominated, everything more expensive is a non-starter.
What could go wrong, and how we know we are not wrong
Section in progress
Failure modes, ethical considerations, and the conditions under which this whitepaper would be falsified are being authored as the weekly cadence ships. The Deutschian commitment: every claim above is a conjecture; we publish the conditions under which we would update. New whitepaper sections ship with each Monday newsletter drop. Subscribe to get the upgrade, or contribute on GitHub.
Who would back this
Capital allocators with a stated thesis or deployed portfolio in this domain. This is a starting list — Exa Websets enrichment will expand it to direct check-writers per company.
Emergent Ventures
Fast grants. High-variance, unconventional, talent-first.
Thiel Fellowship
$100k to stop out of school and build something important.
Deep Science Ventures
Outcome-first venture creation. Define the holy-grail outcome, then recruit founders.
Founders Fund
Contrarian hard tech that rebuilds the industrial base.
Lux Capital
Counter-conventional science at the edges of physics and biology.
What the thinkers say
“Neuralink targets brain and spinal-cord disease as near-term deliverables with long-term implications for human-AI symbiosis and healthspan.”
“Extending healthy human life is a core progress goal. Curing aging is as legitimate a target as curing any single disease.”
“Human lifespan extension is on the canonical list of "good quests that require massively leveled heroes."”
Where this is wrong, tell us
Every number on this page carries a source and a confidence tag. Every section open to refutation. If a citation is wrong, a number is stale, or a conjecture is unfounded — file a correction.
corrections → use the feedback widget in the nav · open issue at github.com/adamtpang/optimism.fun