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Updated: Jan 2, 2026
Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality
Published on: May 5, 2022
DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging
Sophia K Lewis1, Daniel Nachun2, Martin G Martin3
1Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California; Eli and Edythe Broad Stem Cell Research Center, University of California Los Angeles, Los Angeles, California.
Human intestinal organoids retain age-related DNA methylation patterns, with small intestine organoids showing a surprising epigenetic age reduction compared to colon organoids. This validates organoids for studying intestinal aging.
Area of Science:
- Gastroenterology
- Stem Cell Biology
- Epigenetics
Background:
- Intestinal epithelia rely on adult stem cells for rapid turnover.
- Distinct physiological roles exist between the small intestine and colon.
- Age-related changes in stem cell behavior and degenerative processes are not fully understood.
Purpose of the Study:
- To investigate if stem cell-enriched organoids preserve DNA methylation-based aging profiles.
- To determine if organoids maintain hallmarks of aging in the absence of an aging niche.
- To assess regional differences in stem cell aging within the intestine.
Main Methods:
- Utilized standard human methylation arrays.
- Employed the human epigenetic clock as an aging biomarker.
- Analyzed in vitro-derived, 3D, stem cell-enriched intestinal organoids.
Main Results:
- Stem cell-enriched organoids maintained segmental methylation differences.
- Epigenetic age, measured by the epigenetic clock, was preserved in vitro.
- Small intestine organoids exhibited significant epigenetic age reduction compared to colon organoids.
Conclusions:
- Organoids serve as a valid model for studying human intestinal aging.
- The study introduces methods for modeling aging and age-onset diseases in vitro.
- Regional differences in intestinal stem cell aging are evident in organoid models.
