Evidence map›Paper›PMID 41787410›Full record

ArticleBMC biology2026

Modeling age-related methylation changes in vitro with intestinal organoids.

Himani Vaidya, Gennaro Calendo, Kelsey Keith, Anthony Pompetti, Curt Balch, Jozef Madzo, Jaroslav Jelinek, Jean-Pierre J Issa

Abstract read
In one paragraph

Article in BMC biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Himani VaidyaCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Gennaro CalendoCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Kelsey KeithCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Anthony PompettiCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Curt BalchCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Jozef MadzoCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Jaroslav JelinekCoriell Institute for Medical Research, Camden, NJ, 08013, USA.
Jean-Pierre J IssaCoriell Institute for Medical Research, Camden, NJ, 08013, USA. jpissa@coriell.org.

Funding

NIH HHS P50-CA100632NIH HHS P50-CA254897NIH HHS R01-CA214005
6 · The paper itself

Abstract

backgroundIntestinal organoids, three-dimensional cultures derived from intestinal stem cells, serve as a promising model for studying aging. DNA methylation is recognized as a biological clock of aging, and we hypothesized the value of organoid DNA methylation for aging research. To test this, we compared DNA methylation patterns in organoids to those observed in primary aging intestinal epithelium.

resultsOur genome-wide analysis revealed significant DNA methylation changes during organoid establishment and culture. Specifically, 27% of CpG sites exhibited hypomethylation, while 11% gained methylation (hypermethylation). The observed hypermethylation primarily affected CpG islands (14-25% of CpG sites) and corresponded with sites susceptible to age-related methylation in vivo (p < 0.001). Early-passage (P0 and P2) organoids derived from 4- and 24-month-old mice retained aging-specific methylation patterns, with a correlation coefficient of 0.48 (p < 0.001) between in vivo and ex vivo methylation differences. Furthermore, age-related hypermethylation continued to change with passage, with linear modeling using CpG sites that strongly associated with age from a previous dataset indicating that organoids age at an approximate rate of 2 weeks per week in culture. In contrast, hypomethylation primarily (30-36% of CpG sites) occurred in non-aging-associated genomic regions, such as non-promoter, non-CpG island regions (including transposable elements), and showed no correlation with differentiation or aging in vivo.

conclusionsOur findings suggest that DNA methylation changes in organoids reflect two distinct biological processes: aging, as marked by CpG island hypermethylation, and an unexplained stochastic hypomethylation defect. Additionally, treatment with the DNA methylation inhibitor decitabine reduced the methylation age of organoids from 22 to 10 months, demonstrating the potential of organoids as a model for studying extrinsic influences on age-related DNA hypermethylation.

Indexed as

AgingDNA MethylationIntestinal MucosaIntestinesOrganoidsAnimalsCpG IslandsMiceMice, Inbred C57BLModels, BiologicalAgingDNA methylationEpigeneticsIntestinal Epithelial cellsOrganoids

Identifiers

PMID41787410
PMCPMC13077934

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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.