ArticleAging cell2024
Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Biological Versus Technical Reliability of Epigenetic Clocks and Implications for Disease Prognosis and Intervention Response.Aging cell · 2026Article
- Foundations of Gerophysics.Aging · 2026Article
- Pregnancy lab test dynamics resemble rejuvenation of some organs and aging of others.Nature communications · 2026Article
- Review
- Do we actually need aging clocks?npj aging · 2025Review
- No winners or losers: clinical chemistry-based biological aging metrics perform similarly across cohorts and health outcomes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Aging by the clock and yet without a program.Nature aging · 2025Review
- First-generation versus next-generation epigenetic aging clocks: Differences in performance and utility.Biogerontology · 2025Review
- A Novel Framework for the Design of Minimized Epigenetic Clocks Using the Analysis of DNA Methylation Heterogeneity.International journal of molecular sciences · 2025Article
- The COVID-19 legacy: consequences for the human DNA methylome and therapeutic perspectives.GeroScience · 2025Review
- Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.Aging cell · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Epigenetic aging clocks have been widely used to validate rejuvenation effects during cellular reprogramming. However, these predictions are unverifiable because the true biological age of reprogrammed cells remains unknown. We present an analytical framework to consider rejuvenation predictions from the uncertainty perspective. Our analysis reveals that the DNA methylation profiles across reprogramming are poorly represented in the aging data used to train clock models, thus introducing high epistemic uncertainty in age estimations. Moreover, predictions of different published clocks are inconsistent, with some even suggesting zero or negative rejuvenation. While not questioning the possibility of age reversal, we show that the high clock uncertainty challenges the reliability of rejuvenation effects observed during in vitro reprogramming before pluripotency and throughout embryogenesis. Conversely, our method reveals a significant age increase after in vivo reprogramming. We recommend including uncertainty estimation in future aging clock models to avoid the risk of misinterpreting the results of biological age prediction.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.