# Put a biological-age marker in a trial that also measures something a person would notice

Source: https://onco.cc/ideas/idea-rejuv-biological-age-as-a-randomised-endpoint/  
OnCo record `idea-rejuv-biological-age-as-a-randomised-endpoint` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Epigenetic clocks and senescence markers run fast after cancer treatment, and nobody has shown that moving one matters. The way to find out is to make the clock a secondary endpoint in a trial whose primary endpoint is physical function.

## Summary

The measurement side of biological ageing in survivors is in reasonable shape. The intervention side is empty, and the market filling it is not. The design problem is that a trial with a clock as its primary endpoint proves nothing a person would notice, while a trial with a clinical endpoint is expensive, so neither gets run and the question stays open.

The resolution is to stop choosing. Any adequately powered randomised trial of an intervention in survivors should bank samples and prespecify a biological-age secondary analysis: does the marker move, and does movement in the marker track movement in the function endpoint within the same people? Answer that a few times and the field learns whether these markers are worth using as endpoints at all, which is the question that currently blocks every geroprotective trial in oncology.

PROFFi is the first trial with this shape in cancer survivors: fisetin with and without tailored exercise, four arms, with change in six-minute walk distance as the primary endpoint. The cheapest version of this idea is a funder requirement rather than a new trial, attached to the survivorship trials already being paid for.

## Fields

- Kind: Idea
- Last checked: 2026-10-02
- Tags: rejuvenation; survivorship; open-problem; biological-ageing
- Hypothesis: If markers of biological ageing are worth treating, change in them will correlate with change in physical function within randomised participants; if it does not, the markers are descriptive and should not be used as endpoints.
- Rationale: No clock is validated as a clinical test, none is used to make a treatment decision, and no trial has shown that moving a clock changes what happens to a person. The same holds for p16INK4a and for telomere length. Meanwhile senolytics, metformin, rapamycin and NAD+ precursors are all sold or discussed for this purpose with no randomised evidence in survivors, and the trial designed to test metformin as a geroprotector has not started after a decade.
- Proposed test: Prespecify biological-age secondary endpoints, with banked samples, in every publicly funded randomised trial of exercise, rehabilitation or a candidate geroprotective agent in cancer survivors, and pool them. Read out whether within-person change in marker tracks within-person change in the function primary.
- Maturity: early-clinical
- Actor: research

## Sources

- Qin et al., Epigenetic age acceleration and chronic health conditions among adult survivors of childhood cancer (JNCI 2021;113:597-605): https://doi.org/10.1093/jnci/djaa147
- Ness et al., Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: a report from the St Jude Lifetime cohort study (JCO 2013;31:4496-4503): https://doi.org/10.1200/JCO.2013.52.2268
- ClinicalTrials.gov NCT06113016: https://clinicaltrials.gov/study/NCT06113016

## Connected records

- technologies: [Epigenetic age after cancer treatment](https://onco.cc/technologies/rejuv-age-epigenetic-clocks/), [Senescent cells and p16 after chemotherapy](https://onco.cc/technologies/rejuv-age-senescent-cells-after-treatment/), [Senolytics after cancer treatment](https://onco.cc/technologies/rejuv-frontier-senolytics/), [What actually works after treatment](https://onco.cc/technologies/rejuv-frontier-what-works/)
- trials: [PROFFi: fisetin and exercise to prevent frailty in breast cancer survivors](https://onco.cc/trials/rejuv-trial-proffi/)
- roadmaps: [Recovery and rejuvenation roadmap: cure is not enough → survivorship gets a name → the cohorts that measured the cost → exercise proven as treatment → biological ageing measured and sold → repair, if anyone funds it](https://onco.cc/roadmaps/rejuvenation-roadmap/)
- fronts: [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Nobody has tested whether reversing measured biological ageing changes anything](https://onco.cc/bottlenecks/rejuv-agenda-biological-age-as-an-untested-target/)

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