ArticleAging2022
Aging the brain: multi-region methylation principal component based clock in the context of Alzheimer's disease.
Article in Aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- A cell-type-resolved meta-analysis reveals glial DNA methylation changes associated with aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- Pooled it
- Epigenetic Aging and Cognitive Performance in General and Psychiatric Populations: A Systematic Review and Narrative Synthesis.Biological psychiatry global open science · 2026Review
- From aging to Alzheimer's disease: concordant brain DNA methylation changes in late life.Genome medicine · 2026Article
- 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
- Human Brain Cell-Type-Specific Aging Clocks Based on Single-Nuclei Transcriptomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Beyond the Genotype: A Multi-Omic Analysis of APOEe4's Role in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- A Machine-Learning Approach Identifies Rejuvenating Interventions in the Human Brain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of protective genetic variants in modulating epigenetic aging.GeroScience · 2025Article
- Epigenetic clocks and DNA methylation biomarkers of brain health and disease.Nature reviews. Neurology · 2025Review
- Brain DNA Methylation Age, Lifestyle Factors and Dementia in the Swedish Twin Registry.Aging cell · 2025Article
- DoliClock: a lipid-based aging clock reveals accelerated aging in neurological disorders.Aging · 2025Article
- The Impact of Early Life Adversity on Peripubertal Accelerated Epigenetic Aging and Psychopathology.Journal of the American Academy of Child and Adolescent Psychiatry · 2025Article
- Complementary value of molecular, phenotypic, and functional aging biomarkers in dementia prediction.GeroScience · 2025Article
- Age-invariant genes: multi-tissue identification and characterization of murine reference genes.Aging · 2025Article
- Inflammation and DNA methylation in Alzheimer's disease: mechanisms of epigenetic remodelling by immune cell oxidants in the ageing brain.Redox report : communications in free radical research · 2024Review
- Blood-Based Biomarkers in Alzheimer's Disease: Advancing Non-Invasive Diagnostics and Prognostics.International journal of molecular sciences · 2024Review
- Epigenetics in Alzheimer's Disease: A Critical Overview.International journal of molecular sciences · 2024Review
- Age-Invariant Genes: Multi-Tissue Identification and Characterization of Murine Reference Genes.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) risk increases exponentially with age and is associated with multiple molecular hallmarks of aging, one of which is epigenetic alterations. Epigenetic age predictors based on 5' cytosine methylation (DNAm), or epigenetic clocks, have previously suggested that epigenetic age acceleration may occur in AD brain tissue. Epigenetic clocks are promising tools for the quantification of biological aging, yet we hypothesize that investigation of brain aging in AD will be assisted by the development of brain-specific epigenetic clocks. Therefore, we generated a novel age predictor termed PCBrainAge that was trained solely in cortical samples. This predictor utilizes a combination of principal components analysis and regularized regression, which reduces technical noise and greatly improves test-retest reliability. To characterize the scope of PCBrainAge's utility, we generated DNAm data from multiple brain regions in a sample from the Religious Orders Study and Rush Memory and Aging Project. PCBrainAge captures meaningful heterogeneity of aging: Its acceleration demonstrates stronger associations with clinical AD dementia, pathologic AD, and APOE ε4 carrier status compared to extant epigenetic age predictors. It further does so across multiple cortical and subcortical regions. Overall, PCBrainAge's increased reliability and specificity makes it a particularly promising tool for investigating heterogeneity in brain aging, as well as epigenetic alterations underlying AD risk and resilience.
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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.