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Updated: Jul 23, 2025
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Studying Age-dependent Genomic Instability using the S. cerevisiae Chronological Lifespan Model
Published on: September 29, 2011
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More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Christopher J Minteer1, Kyra Thrush1,2, John Gonzalez1
1Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Science Advances
|July 19, 2023
Summary
Aging cells share an epigenetic signature linked to cancer risk. This CellDRIFT signature increases with age and tissue replication, suggesting replication drives epigenetic changes toward a tumorigenic state.
Area of Science:
- Epigenetics
- Cancer Biology
- Aging Research
Background:
- Aging is a primary risk factor for cancer.
- The role of somatic mutations in age-related cancer is established but likely incomplete.
Purpose of the Study:
- To investigate shared epigenetic mechanisms between aging and cancer.
- To identify and characterize an epigenetic signature associated with aging and tumorigenesis.
Main Methods:
- Modeled an epigenetic signature (CellDRIFT) using DNA methylation in passaged immortalized human cells.
- Validated the signature in clinical tissues, correlating it with age, cancer status, and stem cell divisions.
Main Results:
- The CellDRIFT signature increased with age across multiple tissues.
- CellDRIFT distinguished tumor from normal tissue and was elevated in normal breast tissue of cancer patients.
- The signature was transiently reset upon cellular reprogramming and correlated with stem cell divisions and cancer risk.
Conclusions:
- Aging and cancer share a common epigenetic replication signature (CellDRIFT).
- Cellular replication may drive age-related epigenetic alterations, potentially promoting a tumorigenic state.
- CellDRIFT serves as a potential biomarker for aging-related cancer risk.
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