ArticleNature aging2024
Quantifying the stochastic component of epigenetic aging.
Article in Nature aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cosmetogenomics unveiled: a systematic review of AI, genomics, and the future of personalized skincare.Frontiers in artificial intelligence · 2025Pooled it
- Trial
- Article
- DNA methylation variability provides a complementary epigenetic signature of aging heterogeneity: Findings from the Canadian Longitudinal Study on Aging and the Baltimore Longitudinal Study of Aging.bioRxiv : the preprint server for biology · 2026Article
- Responsiveness of epigenetic aging biomarkers to longevity interventions in humans.Nature medicine · 2026Article
- Tissue-Level Transcriptomic Entropy Reveals Organ-Specific Aging Patterns and Predicts Cancer Progression.Aging cell · 2026Article
- Natural-Product-Derived Antioxidants and DNA Methylation-Based Epigenetic Aging: A Systematic Review of Human Intervention Studies.Antioxidants (Basel, Switzerland) · 2026Review
- Embracing non-linearity in human ageing.Nature reviews. Genetics · 2026Review
- The OmniAge compendium of aging omic biomarkers links mitotic clocks to clonal hematopoiesis and causality.Nature communications · 2026Article
- Article
- Epigenetic mechanisms of gingival aging: biological basis, periodontal implications, and therapeutic perspectives.Odontology · 2026Review
- Epigenetic signatures of cardiometabolic risk in men: accelerated aging and differential methylation replicated across cohorts.Clinical epigenetics · 2026Article
- Systemic epigenetic dysregulation as a driver of ageing and a therapeutic target.Nature reviews. Molecular cell biology · 2026Review
- The Evolving Landscape of Clinical Aging Clocks: From Epigenetic to Multi-Omics Integration.Aging cell · 2026Review
- Epigenetic Aging in Brain Tissue of the Self-Fertilizing Vertebrate,Ecology and evolution · 2026Article
- Foundations of Gerophysics.Aging · 2026Article
- Proteomic aging clocks in epidemiological studies: advances, applications and prospects.Nature aging · 2026Review
- An Extracellular Matrix Aging Clock Based on Circulating Matrisome Proteins Predicts Biological Aging and Disease.Aging cell · 2026Article
- Article
- OMICmAge quantifies biological age by integrating multi-omics with electronic medical records.Nature aging · 2026Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
DNA methylation clocks can accurately estimate chronological age and, to some extent, also biological age, yet the process by which age-associated DNA methylation (DNAm) changes are acquired appears to be quasi-stochastic, raising a fundamental question: how much of an epigenetic clock's predictive accuracy could be explained by a stochastic process of DNAm change? Here, using DNAm data from sorted immune cells, we build realistic simulation models, subsequently demonstrating in over 22,770 sorted and whole-blood samples from 25 independent cohorts that approximately 66-75% of the accuracy underpinning Horvath's clock could be driven by a stochastic process. This fraction increases to 90% for the more accurate Zhang's clock, but is lower (63%) for the PhenoAge clock, suggesting that biological aging is reflected by nonstochastic processes. Confirming this, we demonstrate that Horvath's age acceleration in males and PhenoAge's age acceleration in severe coronavirus disease 2019 cases and smokers are not driven by an increased rate of stochastic change but by nonstochastic processes. These results significantly deepen our understanding and interpretation of epigenetic clocks.
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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.