Evidence map›Paper›PMID 40336042›Full record

ArticleClinical epigenetics2025

Genetic and environmental contributions to epigenetic aging across adolescence and young adulthood.

Dmitry V Kuznetsov, Yixuan Liu, Alicia M Schowe, Darina Czamara, Jana Instinske, Charlotte K L Pahnke, Markus M Nöthen, Frank M Spinath, Elisabeth B Binder, Martin Diewald and 3 more

Abstract readTwin Study
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Dmitry V KuznetsovBielefeld University, Bielefeld, Germany. dmitry.kuznetsov@uni-bielefeld.de.
Yixuan LiuBielefeld University, Bielefeld, Germany.
Alicia M SchoweDepartment Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.
Darina CzamaraDepartment Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.
Jana InstinskeUniversity of Bremen, Bremen, Germany.
Charlotte K L PahnkeInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany.
Markus M NöthenInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany.
Frank M SpinathDepartment of Psychology, Saarland University, Saarbrücken, Germany.
Elisabeth B BinderDepartment Genes and Environment, Max Planck Institute of Psychiatry, Munich, Germany.
Martin DiewaldBielefeld University, Bielefeld, Germany.
Andreas J ForstnerInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany.
Christian KandlerBielefeld University, Bielefeld, Germany.
Bastian MönkediekBielefeld University, Bielefeld, Germany.

Funding

Deutsche Forschungsgemeinschaft 220286500Deutsche Forschungsgemeinschaft 428902522Deutsche Forschungsgemeinschaft 458609264
6 · The paper itself

Abstract

backgroundEpigenetic aging estimators commonly track chronological and biological aging, quantifying its accumulation (i.e., epigenetic age acceleration) or speed (i.e., epigenetic aging pace). Their scores reflect a combination of inherent biological programming and the impact of environmental factors, which are suggested to vary at different life stages. The transition from adolescence to adulthood is an important period in this regard, marked by an increasing and, then, stabilizing epigenetic aging variance. Whether this pattern arises from environmental influences or genetic factors is still uncertain. This study delves into understanding the genetic and environmental contributions to variance in epigenetic aging across these developmental stages. Using twin modeling, we analyzed four estimators of epigenetic aging, namely Horvath Acceleration, PedBE Acceleration, GrimAge Acceleration, and DunedinPACE, based on saliva samples collected at two timepoints approximately 2.5 years apart from 976 twins of four birth cohorts (aged about 9.5, 15.5, 21.5, and 27.5 years at first and 12, 18, 24, and 30 years at second measurement occasion).

resultsHalf to two-thirds (50-68%) of the differences in epigenetic aging were due to unique environmental factors, indicating the role of life experiences and epigenetic drift, besides measurement error. The remaining variance was explained by genetic (Horvath Acceleration: 24%; GrimAge Acceleration: 32%; DunedinPACE: 47%) and shared environmental factors (Horvath Acceleration: 26%; PedBE Acceleration: 47%). The genetic and shared environmental factors represented the primary sources of stable differences in corresponding epigenetic aging estimators over 2.5 years. Age moderation analyses revealed that the variance due to individually unique environmental sources was smaller in younger than in older cohorts in epigenetic aging estimators trained on chronological age (Horvath Acceleration: 47-49%; PedBE Acceleration: 33-68%). The variance due to genetic contributions, in turn, potentially increased across age groups for epigenetic aging estimators trained in adult samples (Horvath Acceleration: 18-39%; GrimAge Acceleration: 24-43%; DunedinPACE: 42-57%).

conclusionsTransition to adulthood is a period of the increasing variance in epigenetic aging. Both environmental and genetic factors contribute to this trend. The degree of environmental and genetic contributions can be partially explained by the design of epigenetic aging estimators.

Indexed as

AgingEpigenesis, GeneticGene-Environment InteractionAdolescentAdultChildDNA MethylationFemaleHumansLongitudinal StudiesMaleSalivaYoung AdultAdolescenceAge moderationDunedinPACEEpigenetic agingGene‒environment interactionGrimAgeHorvath clockPedBE clock

Identifiers

PMID40336042
PMCPMC12060359

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Registered trials

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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.