DNA Methylation, Aging, and Cancer

Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-asso...

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Main Authors: Himani Vaidya, Jaroslav Jelinek, Jean-Pierre J. Issa
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Epigenomes
Subjects:
Online Access:https://www.mdpi.com/2075-4655/9/2/18
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author Himani Vaidya
Jaroslav Jelinek
Jean-Pierre J. Issa
author_facet Himani Vaidya
Jaroslav Jelinek
Jean-Pierre J. Issa
author_sort Himani Vaidya
collection DOAJ
description Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-associated changes in DNA methylation, characterized by both global hypomethylation and focal hypermethylation, contribute to the emergence of cancer. We discuss mechanisms of DNA methylation drift, the development of epigenetic clocks, and the role of entropy and epigenetic mosaicism, in aging and tumorigenesis. Emphasis is placed on how stochastic methylation errors accumulate in aging cells and lead to epiallelic shifts and gene silencing, predisposing tissues to malignant transformation, even despite recently increased cancer incidences at younger ages. We also highlight the translational potential of DNA methylation-based biomarkers, and therapeutic targets, in age-related diseases. By framing cancer as a disease of accelerated epigenetic aging, this review offers a unifying perspective and calls for age-aware approaches to both basic research and clinical oncology.
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spelling doaj-art-1972bd2d1ecc4514b41b5f474151236f2025-08-20T03:27:10ZengMDPI AGEpigenomes2075-46552025-06-01921810.3390/epigenomes9020018DNA Methylation, Aging, and CancerHimani Vaidya0Jaroslav Jelinek1Jean-Pierre J. Issa2Coriell Institute for Medical Research, Camden, NJ 08103, USACoriell Institute for Medical Research, Camden, NJ 08103, USACoriell Institute for Medical Research, Camden, NJ 08103, USAAging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-associated changes in DNA methylation, characterized by both global hypomethylation and focal hypermethylation, contribute to the emergence of cancer. We discuss mechanisms of DNA methylation drift, the development of epigenetic clocks, and the role of entropy and epigenetic mosaicism, in aging and tumorigenesis. Emphasis is placed on how stochastic methylation errors accumulate in aging cells and lead to epiallelic shifts and gene silencing, predisposing tissues to malignant transformation, even despite recently increased cancer incidences at younger ages. We also highlight the translational potential of DNA methylation-based biomarkers, and therapeutic targets, in age-related diseases. By framing cancer as a disease of accelerated epigenetic aging, this review offers a unifying perspective and calls for age-aware approaches to both basic research and clinical oncology.https://www.mdpi.com/2075-4655/9/2/18DNA methylationagingcancer
spellingShingle Himani Vaidya
Jaroslav Jelinek
Jean-Pierre J. Issa
DNA Methylation, Aging, and Cancer
Epigenomes
DNA methylation
aging
cancer
title DNA Methylation, Aging, and Cancer
title_full DNA Methylation, Aging, and Cancer
title_fullStr DNA Methylation, Aging, and Cancer
title_full_unstemmed DNA Methylation, Aging, and Cancer
title_short DNA Methylation, Aging, and Cancer
title_sort dna methylation aging and cancer
topic DNA methylation
aging
cancer
url https://www.mdpi.com/2075-4655/9/2/18
work_keys_str_mv AT himanivaidya dnamethylationagingandcancer
AT jaroslavjelinek dnamethylationagingandcancer
AT jeanpierrejissa dnamethylationagingandcancer