New York City – September 15, 2026 -- Mice fed 30 percent fewer calories than their normal intake showed reduced levels of DNA mutations across multiple tissues, according to a study published September 9 in Cell by researchers at NYU Langone Health and University Hospitals Cleveland.
Researchers Measure Genome-Wide Mutation Reduction for the First Time
The study is the first to quantify how caloric restriction affects mutation patterns across a large portion of the genome, rather than in single genes as prior research had done. Using advanced DNA sequencing technology, the team tracked both substitution mutations, where one DNA letter replaces another, and insertion-deletion mutations, where DNA letters are added or removed.
The research was conducted in collaboration with the University of Texas Southwestern Medical Center and the National Institutes of Health.
Liver Cells Show Greater Mutation Reduction Than Kidney or Brain Cells
Caloric restriction's impact varied by tissue type, with liver cells showing a larger drop in mutation burden than kidney or brain cells. The authors attribute this to differences in how DNA damage occurs and is repaired across distinct cell types.
Least Active Genomic Regions Benefit Most From Reduced Caloric Intake
In liver and kidney cells, the largest mutation reductions occurred in genomic regions with no active genes or genes unused by that particular cell type. Study co-author Jonathan Shoag, MD, of University Hospitals Cleveland and Case Western Reserve University School of Medicine, called the finding unexpected. One explanation offered by the authors is that actively used genomic regions already undergo frequent DNA repair, limiting additional benefit from reduced damage.
Gilad D. Evrony, MD, PhD, co-corresponding author and core member of the Center for Human Genetics and Genomics at NYU Langone, noted that calorie-restricted mice remain healthier for longer, though the diet is too extreme for human application. He said the findings open a path toward understanding how to lower mutation levels tied to cancer and other age-related diseases without requiring extreme dietary restriction.
Funding Includes NIH Grants and Multiple Private Foundations
The study received support from NIH grants T32AG052909, F32AG076287, and UH3NS132024, along with funding from the Pew Charitable Trusts, the Jacob Goldfield Foundation, the Damon Runyon Cancer Research Foundation, the Smythe Family Impact Fund, the Vail family, and the Howard Hughes Medical Institute. Additional authors included researchers from the National Institute on Aging's Translational Gerontology Branch and the University of Texas Southwestern's Department of Neuroscience.