Epigenetic clocks
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Statistical predictors of chronological age built from DNA methylation levels at selected CpG sites. Steve Horvath's 2013 multi-tissue clock used 353 sites and predicted chronological age across most human tissues with a median error of a few years; Hannum's blood-based clock appeared the same year. Second-generation clocks — PhenoAge, GrimAge — were trained on mortality and clinical measures rather than on chronological age and predict health outcomes better, and DunedinPACE was trained on the longitudinal rate of change of multiple organ-system measures, so it estimates a pace rather than an age. The gap between a clock reading and chronological age is associated with mortality risk. What no clock has yet shown is that it is a valid surrogate: that changing the reading changes the outcome. Until an intervention is shown to move both the clock and the clinical endpoint in the same direction in the same trial, a clock is a correlate of ageing rather than a measure of it, and the commercial tests sold on that basis are ahead of their evidence.
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Evidence · 2
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Connections · 1
- The missing surrogate endpoint for ageinginstance_of
Assembled narrative · 1
Assembled from 20 blocks · 2 evidence · 11 related
- Story
- Statistical predictors of chronological age built from DNA methylation levels at selected CpG sites. Steve Horvath's 2013 multi-tissue clock used 353 sites and predicted chronological age across most human tissues with a median error of a few years; Hannum's blood-based clock appeared the same year. Second-generation clocks — PhenoAge, GrimAge — were trained on mortality and clinical measures rather than on chronological age and predict health outcomes better, and DunedinPACE was trained on the longitudinal rate of change of multiple organ-system measures, so it estimates a pace rather than an age. The gap between a clock reading and chronological age is associated with mortality risk. What no clock has yet shown is that it is a valid surrogate: that changing the reading changes the outcome. Until an intervention is shown to move both the clock and the clinical endpoint in the same direction in the same trial, a clock is a correlate of ageing rather than a measure of it, and the commercial tests sold on that basis are ahead of their evidence.
- Knowledge
- Epigenetic clocks
- The missing surrogate endpoint for ageing
- Connections
- CALERIE (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy)
- The missing surrogate endpoint for ageing
- The multi-tissue epigenetic clock is published
- Caloric restriction is reported to slow a pace-of-ageing measure
- Healthspan
- Senolytics
- TAME — Targeting Aging with Metformin
- Epigenetic clocks
- TAME is proposed as the first trial with an ageing endpoint
- Senolytics reach human patients for the first time
- Caloric restriction is reported to slow a pace-of-ageing measure
- Evidence
- Supports the multi-tissue epigenetic age predictor and its construction from 353 CpG sites. V55 verification basis: not retrieved; the article number is given as recalled and must be confirmed.
- Supports the reported slowing of the DunedinPACE pace-of-ageing measure under caloric restriction, without significant effects on first-generation epigenetic clocks. V55 verification basis: not retrieved; the effect size is deliberately described qualitatively because the producer could not confirm the figure.
Observed changes · 0
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