Eating less is one of the oldest ideas in aging research. In lab animals, a big cut in calories has long been tied to longer lives and slower aging1. A study published on September 9 in the journal Cell now adds a new piece: mice fed 30% fewer calories than they would eat on their own built up fewer DNA mutations in several organs1. The effect was not the same everywhere. It was stronger in the liver than in the kidney or brain, and it was strongest in quiet stretches of DNA1.
This is the first Biohack article on this subject. The work was done in mice, not people.
What the researchers did
DNA is written in a code of chemical “letters.” Over a lifetime, every cell picks up changes in those letters, called mutations, when DNA gets damaged or when the cell makes mistakes fixing or copying it1. Most of these changes are harmless. When they hit important genes, they can lead to cancer and other diseases1.
Earlier studies had looked at how calorie cutting affects mutations in single genes. This team looked across a large part of the genome, the full set of DNA in a cell, which the researchers say had not been done before1. They used a very accurate DNA reading method to count mutations1. Coverage of the study names it as “nanorate sequencing” and says the team looked at kidney, liver and brain cells2.
Two groups of mice were compared: one allowed to eat freely and one fed 30% fewer calories1. According to Wisevoter’s summary, the mice were studied between 6 and 19 months of age, and tissues were collected at 19 months2. The sources do not say how many mice were in each group.
What they found
The lower-calorie diet reduced two kinds of mutation, to different degrees in different tissues1:
- Swaps, where one DNA letter is replaced by another (scientists call these substitutions).
- Additions and losses, where one or more letters are added or missing (insertions and deletions).
Wisevoter reported that the biggest drops showed up in a pattern called SBS5, a well-known signature of mutations that pile up with age2.
Not the same in every organ
Liver cells showed a larger drop in mutations than kidney or brain cells1. The authors said this fits with how different these cell types are, and how differently each one gets damaged and repairs its DNA1.
Biggest effect in the quiet parts of DNA
The result that surprised the team was where in the DNA the effect showed up. In liver and kidney cells, the drop was largest in the least active regions: stretches with no genes, or with genes the cell is not using1. One possible reason, the authors said, is that if eating less cuts DNA damage everywhere, the busy regions gain less because cells already repair damage there often1.
“We didn’t expect to find this asymmetry across the genome,” said co-corresponding author Jonathan Shoag, MD, an associate professor in the Department of Urology at University Hospitals Cleveland and Case Western Reserve University School of Medicine.
What it does not show yet
This is a mouse study. It does not show that the same thing happens in people, and it was not designed to. Gilad Evrony, a co-lead author at NYU Langone, said the mouse diet “is too challenging for humans”1. Wisevoter’s summary also notes that the findings do not offer diet advice for people, since the work is still at the animal stage2.
It also does not show that fewer mutations are why calorie-cut animals live longer. A Japanese-language commentary on the study, published on the platform note, made this point directly. It said that while mutations are known to build up with age, how much they drive aging in the whole body is still debated, and it cited a 2026 review that found direct evidence for mutations as a main cause of aging to be limited3. The same commentary called the authors’ explanation for the quiet-DNA effect a hypothesis, and said the exact mechanism behind the drop in mutations is not settled by this study alone3.
The commentary also warned that heavy calorie cutting in people can, depending on the situation, bring other problems such as poor nutrition, loss of muscle and effects on bone3.
Who did the work and who paid for it
The study was led by researchers at NYU Langone Health and University Hospitals Cleveland, working with the University of Texas Southwestern Medical Center and the National Institutes of Health1. The first author is Marta Grońska-Pęski, a postdoctoral fellow in Evrony’s lab1. The mouse group on the diet was set up by Victoria Acosta-Rodríguez, Joseph Takahashi and Carla Green, according to Evrony1.
Funding came from National Institutes of Health grants, 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 Institute1. Evrony holds a named professorship at NYU Grossman School of Medicine, the Jacob D. Goldfield Associate Professor of Pediatrics and Neuroscience1. The sources do not mention any company behind the work or any product tied to it.
How it fits the field
Calorie cutting has been studied for decades. Research in flies, worms and mice has shown it can extend life in the lab, but whether it does the same for people remains unclear4.
The main human evidence comes from a trial called CALERIE, described by Yale as the first controlled study of calorie cutting in healthy people4. In that trial, more than 200 people took part, and some were asked to eat 14% fewer calories for two years while the rest ate as usual4. A Yale-led analysis published in 2022 reported changes in the thymus, a gland that makes immune cells, and in the activity of genes in body fat4. That trial did not look at DNA mutations in the way the new mouse study did, and the cut in calories was much smaller than the 30% used in the mice.
So the new study links two things that were each known on their own: that eating less tends to slow aging in animals, and that mutations build up with age. As Evrony put it in NYU Langone’s release:
“While links between diet and lifespan have been established in animals, our results show that diet and mutations across the genome are also linked,”
What to watch next
The researchers are not aiming to get people to eat 30% less. Shoag said the team hopes to test more diets and look at mutations in more tissues and cell types to learn what drives the link1. First author Grońska-Pęski said understanding the mechanisms could eventually point to ways of reducing mutations “without the challenges and risks of an extreme diet”1.
Questions to follow:
- Whether other teams find the same drop in mutations, and the same pattern across organs and DNA regions.
- Whether the effect can be traced to less DNA damage, better repair, or something else.
- Whether any drug or milder diet can produce the same change without heavy calorie cutting, which the authors and coverage both name as the long-term goal12.
- Whether fewer mutations in mice can be tied to fewer cancers or longer life, which this study did not show.
For now, the finding is a measured change in DNA in lab mice on a strict diet. It is not a test of a diet in people.
