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Can We Reverse Aging? Study Explores Genetic and Epigenetic Interplay

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New findings from researchers at the University of California San Diego School of Medicine have clarified the interplay between two major molecular contributors to aging: genetic mutations and epigenetic modifications. Published in Nature Aging, the study explores the relationship between these factors, challenging long-held assumptions and reshaping perspectives on the biology of aging.

Examining aging at the molecular level

Two main theories have dominated the discussion around aging. The somatic mutation theory attributes aging to the accumulation of permanent changes in the DNA sequence, which arise randomly over time. On the other hand, the epigenetic clock theory links aging to reversible chemical modifications to DNA that influence which genes are active or inactive. These epigenetic changes occur predictably and have been widely used as a metric for assessing the biological age of cells.


Somatic mutations

Somatic mutations are changes in the DNA sequence that occur in non-reproductive cells. These mutations are not inherited but can accumulate over a lifetime due to environmental factors, errors during cell division or exposure to mutagens.

Epigenetic modifications

These are chemical changes to DNA or histone proteins that do not alter the DNA sequence itself but affect how genes are expressed. Examples include DNA methylation and histone acetylation, which can turn genes on or off.


Despite their differences, both mechanisms contribute to molecular aging. Researchers have long speculated about a potential connection between genetic mutations and epigenetic alterations. The new study provides evidence for this link.

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Investigating genetic and epigenetic interplay

Using data from the Cancer Genome Atlas and the Pan-Cancer Analysis of Whole Genomes, researchers analyzed the genomes of 9,331 individuals. They identified correlations between genetic mutations and a specific type of epigenetic change known as DNA methylation. Intriguingly, mutations were found to trigger cascading epigenetic changes, often far from the original mutation site. This finding suggests that somatic mutations can drive extensive epigenetic alterations.  


DNA methylation

This is a specific epigenetic modification where methyl groups are added to DNA molecules. DNA methylation often represses gene expression and plays a role in regulating cellular functions, development and aging.


The research also demonstrated that genetic mutations and epigenetic modifications could be used interchangeably to predict biological age, further cementing their connection.

Implications for aging and anti-aging interventions

The study raises important questions about current approaches to combating aging. While efforts to reverse epigenetic changes are a growing focus in anti-aging research, the findings suggest that these interventions may address symptoms of aging rather than its root causes. If genetic mutations are the primary drivers of aging, reversing epigenetic changes alone may have limited effects.

"If somatic mutations are the fundamental driver of aging and epigenetic changes simply track this process, it’s going to be a lot harder to reverse aging than we previously thought."


Dr. Steven Cummings.

Further studies are needed to fully understand the relationship between genetic mutations and epigenetic modifications. However, the work represents a significant step toward unraveling the complexities of aging and offers valuable insights for the development of future therapies.


Reference: Koch Z, Li A, Evans DS, Cummings S, Ideker T. Somatic mutation as an explanation for epigenetic aging. Nat Aging. 2025. doi: 10.1038/s43587-024-00794-x


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