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The missing surrogate endpoint for ageing

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The structural obstacle that shapes the entire field. To show that an intervention slows human ageing you would have to follow a large cohort for decades to death or to disability — a trial nobody can fund, staff or wait for. The alternative is a surrogate: a measurable quantity that changes early, that responds to the intervention, and whose change reliably predicts the change in the real outcome. Cholesterol is the model case, and it took decades and several failed surrogates to establish. Ageing has candidates — epigenetic clocks, frailty indices, grip strength, gait speed, inflammatory markers, multi-omic composites — and none validated. This is why TAME was designed around a composite disease endpoint rather than a biomarker, why senolytic trials measure walking distance, and why a company can sell a biological-age test without making any claim a regulator would have to assess. A reader can use it as a filter: if a longevity claim does not say what endpoint was measured and over what interval, it has not made a testable claim.

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