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Author Spotlight: Generation and Manipulation of Rat Intestinal Organoids
Published on: June 23, 2023
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Modeling age-related methylation changes in vitro with intestinal organoids
Himani Vaidya1, Gennaro Calendo1, Kelsey Keith1,2
1Coriell Institute for Medical Research, Camden, NJ, 08013, USA.
BMC Biology
|March 5, 2026
Summary
Intestinal organoids show DNA methylation changes reflecting aging, with hypermethylation correlating to in vivo aging. These organoids can model aging and the impact of interventions on DNA methylation.
Area of Science:
- Aging research
- Epigenetics
- Stem cell biology
Background:
- Intestinal organoids are advanced 3D cultures from intestinal stem cells, offering a promising model for aging studies.
- DNA methylation serves as a key biomarker for biological aging.
- This study investigated the utility of organoid DNA methylation for aging research by comparing it to primary intestinal epithelium.
Purpose of the Study:
- To compare DNA methylation patterns in intestinal organoids with those in primary aging intestinal epithelium.
- To determine if organoid DNA methylation can accurately reflect aging processes.
- To explore the potential of organoids in studying factors influencing age-related DNA methylation.
Main Methods:
- Genome-wide DNA methylation analysis of intestinal organoids and primary intestinal epithelium.
- Comparison of methylation patterns between in vivo and ex vivo models.
- Linear modeling to assess the rate of aging in organoids.
- Treatment of organoids with decitabine, a DNA methylation inhibitor.
Main Results:
- Significant DNA methylation changes were observed during organoid culture, with 27% of CpG sites showing hypomethylation and 11% showing hypermethylation.
- Hypermethylation in organoids primarily affected CpG islands and correlated with age-related methylation changes observed in vivo.
- Early-passage organoids from aged mice retained aging-specific methylation patterns, and organoids exhibited an aging rate of approximately 2 weeks per week in culture.
- Hypomethylation occurred in non-aging-associated regions and did not correlate with in vivo aging or differentiation.
Conclusions:
- DNA methylation changes in organoids represent both aging (CpG island hypermethylation) and a separate stochastic hypomethylation process.
- Organoids demonstrate potential as a model for studying extrinsic influences on age-related DNA hypermethylation.
- Decitabine treatment reduced the methylation age of organoids, highlighting their utility for intervention studies.
