Study claims that a popular diet may accelerate aging

A strict form of the keto diet has been linked to faster cellular aging in males, while females on the same plan did not show the same damage. 

The difference appears to come down to sex hormones and how they shape the way cells handle stress.

In this new work, male animals on a very high fat, very low carbohydrate diet built up damaged, nondividing cells in the heart and kidneys over just a few weeks, while females were largely spared the same burden. 

The experiments were run by a team at UT Health San Antonio, raising sharp questions about whether similar patterns could emerge in men who stay on keto diets for long stretches of time.

Keto diet and aging

The work was led by David Gius, MD, PhD, a professor of radiation oncology at UT Health San Antonio. His research focuses on how metabolism, hormones, and stress inside cells shape aging and disease across different tissues.

In simple terms, the ketogenic diet, a very low carbohydrate, high fat way of eating, is designed to push the body away from sugar and toward fat as its main energy source. 

“The keto diet is a very low-carbohydrate, high fat way of eating that shifts the body’s primary energy source from carbohydrates to fat,” explained Michelle Routhenstein, MS, RD, CDCES, CDN.

When carb intake stays low enough, the liver produces ketones, small fuel molecules made from fat that can power the brain and other organs when glucose is scarce. 

Carefully planned ketogenic programs are a long standing therapy for drug resistant epilepsy, and a pediatric hospital keto clinic has reported large seizure reductions in many children without major growth problems.

Studying aging and keto diets

In one mouse study, male animals fed a keto diet for several weeks showed a spike in markers of cellular aging called senescence, a state where stressed cells stop dividing but stay alive and inflamed. 

These senescent cells piled up in the heart and kidney, along with higher levels of inflammatory molecules in the blood.

Female mice on the same diet did not show the same surge in senescent cells or inflammatory signals over that time window. 

Their heart and kidney tissue stayed closer to normal, even though their blood ketone levels confirmed they were in ketosis just like the males.

The male mice also showed strong signs of oxidative stress, an overload of reactive oxygen containing molecules that chip away at fats, proteins, and DNA. 

Damage markers such as oxidized lipids and modified proteins climbed in male organs on keto, while female tissues again remained largely unchanged under the same feeding plan.

Older female mice with naturally lower estrogen levels began to look more like the males when they were placed on a ketogenic diet. 

They developed more senescent cells and oxidative damage, linking the protection seen in younger females to hormone status rather than sex alone.

Hormones, oxidative stress, and aging cells

To test that idea directly, the team treated some male mice with estrogen, a major female sex hormone that also influences metabolism and blood vessels. 

Those males no longer showed the keto driven rise in senescent cells or oxidative damage, suggesting that estrogen was actively buffering their tissues against stress.

This protective role fits with broader research showing that estrogen can tune up the cell’s own defense systems. 

In humans, estrogen replacement therapy has been shown to switch on antioxidant and longevity related genes and to lower several measures of oxidative stress, supporting the idea that hormone status changes how tissues weather metabolic strain.

The group also tried a different route, giving male mice classic antioxidants, compounds that neutralize reactive oxygen molecules before they harm cell structures. 

Agents such as N-acetylcysteine, alpha lipoic acid, vitamin C, and a drug that mimics the antioxidant enzyme MnSOD, all cut back the buildup of senescent cells and oxidative damage in keto fed males.

Those antioxidant treatments also brought inflammatory blood markers down toward normal in the male mice. 

Together, the hormone and antioxidant experiments suggest that the diet itself creates extra oxidative pressure, but hormones and chemical defenses can either blunt or amplify the impact on aging cells.

Keto in real people, risks and uses

Animal work like this does not translate directly to humans, which the researchers themselves stressed. 

“Although we can gain insight into metabolic processes through studies defining effects of a keto diet in mice, we do not yet extrapolate those findings in humans,” said Jason Ng, MD, BA, who teaches endocrinology and metabolism in the Department of Medicine at the University of Pittsburgh.

Still, human data already show that keto style patterns are not neutral for the heart and blood vessels. 

In a randomized feeding trial, healthy young women following a ketogenic low carbohydrate high fat diet developed very high LDL cholesterol levels compared with when they ate a more conventional non keto diet.

A broad cardiology review concludes that low carbohydrate patterns can bring quick drops in weight, blood pressure, and blood sugar, yet they do not outperform other eating styles for long term cardiovascular outcomes. 

That review also flags safety questions, including nutrient gaps, kidney strain, and possible effects on arterial plaques.

Separate work in male mice found that long periods of keto feeding led to fat buildup in the liver and worse glucose control, changes that eased after switching back to standard chow in one experiment. 

These mixed findings underline that keto is a strong metabolic tool, not a harmless shortcut, and responses can vary across bodies and over time.

Aging lessons from keto diets

The new mouse work suggests that deep carb restriction might speed the accumulation of senescent cells in some tissues, at least in male animals with typical hormone levels. 

That kind of cellular aging is linked in other research to stiffer hearts, weaker kidneys, and chronic low grade inflammation as organisms grow older.

At the same time, ketogenic therapy remains a vital option for some people with severe epilepsy when other drugs fail. 

“In some cases, particularly for specific medical conditions like epilepsy, a medically supervised keto or modified low carb approach can be beneficial,” said Routhenstein, who emphasized the need for professional guidance when such a restrictive diet is used.

For people drawn to keto mainly for weight loss or short term glucose control, the picture is more unsettled. 

The new findings add sex and hormone status to a growing list of factors that likely shape who does well, who runs into trouble, and how long such a diet should reasonably continue.

Across all of this research, one message stands out clearly: very low carbohydrate, very high fat diets act as powerful metabolic stress tests. 

Anyone considering them as a lifestyle choice, rather than a time limited medical therapy, needs careful medical supervision, regular lab checks, and an honest look at whether less extreme changes could meet their goals.

The study is published in Cell Reports.

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