Calorie Restriction Reduced DNA Mutations Across the Mouse Genome
Mice fed 30% fewer calories carried fewer DNA mutations in several tissues, with the largest drop in the liver and in the quietest parts of the genome, a Cell study from NYU Langone reports.
Founding Editor & Reporter
Eating 30% fewer calories reduced DNA mutations across several tissues in mice, according to a study published in Cell on September 9, 2026.
Researchers at NYU Langone Health and University Hospitals Cleveland, working with the University of Texas Southwestern Medical Center and the National Institutes of Health, used high-accuracy sequencing to measure mutations across a large share of the genome. Earlier work had looked at single genes. This is the first look at how caloric restriction changes mutation patterns that widely, the authors said.
Background
Mutations are changes in the letters of DNA. They accumulate with age as DNA is damaged or copied incorrectly. Most do nothing. Some disrupt genes and contribute to cancer and other diseases.
Caloric restriction — a large, sustained cut in calories — extends lifespan and slows aspects of aging in animals. Whether it also slows the rate at which mutations build up across the genome had not been tested.
The restricted mice were fed 30% less than animals allowed to eat freely. To varying degrees by tissue, the diet lowered both substitution mutations, in which one DNA letter replaces another, and insertions and deletions, in which letters are added or lost.
Gilad D. Evrony, co-corresponding author and a member of NYU Langone’s Center for Human Genetics and Genomics, said the result ties diet to mutations across the genome, not only to lifespan. He also said a diet this strict is too hard for people to sustain, and that the useful next step is to understand how the mutation drop happens.
Where the Effect Was Strongest
The size of the effect depended on the tissue and the cell type. Liver cells lost more of their mutation burden than kidney or brain cells. The authors said that fits how differently DNA is damaged and repaired from one cell type to another.
In liver and kidney, the biggest reduction was in the least active parts of the genome — regions with no genes, or genes that cell is not using. One explanation the authors offer is that active regions already repair DNA damage often, so a diet that lowers damage everywhere would show up more clearly in the regions that are usually repaired less.
Jonathan Shoag, co-corresponding author and a urologist at University Hospitals Cleveland and Case Western Reserve University, said the team had not expected that split across the genome. First author Marta Grońska-Pęski, a postdoctoral fellow in Evrony’s lab, said understanding the mechanism could eventually point to ways of reducing mutations without an extreme diet.
The mouse cohort was established by Victoria Acosta-Rodríguez, Joseph Takahashi, and Carla Green. NIH grants T32AG052909, F32AG076287, and UH3NS132024 supported the work, along with the Pew Charitable Trusts, the Jacob Goldfield Foundation, the Damon Runyon Cancer Research Foundation, and the Howard Hughes Medical Institute.
The Study at a Glance
- Paper: Published in Cell, September 9, 2026
- Lead centers: NYU Langone Health and University Hospitals Cleveland
- Also involved: UT Southwestern and the National Institutes of Health
- Intervention: 30% fewer calories than free feeding
- Finding: Fewer substitution, insertion, and deletion mutations
- Strongest tissue effect: Liver, ahead of kidney and brain
- Strongest genomic effect: The least active regions of the genome, in liver and kidney
Disclaimer
This content is for informational and educational purposes only and is not medical advice. Always consult a qualified healthcare professional before making changes to your health.
