Aging muscle trades strength for self-protection, and reversing that regrew it in mice

A fat molecule that shapes the inner membrane of mitochondria may explain why aging muscle shifts from fast, powerful fibers toward slower ones, and putting some of it back brought wasted muscle back in mice. The work comes from the University of Copenhagen and was published in Nature Aging in 2026. All of the rescue results were in mice, and no treatment for people follows from them.

The day in tech, in one email: TLDR is the daily newsletter with links and TLDRs of the most interesting stories in startups, tech and programming.

Get TLDR →

We may earn a commission if you sign up.

Fabian Finger is first author and co-corresponding author of the paper, and Zachary Gerhart-Hines, an associate professor at the university’s NNF Center for Basic Metabolic Research, is senior author. Scientists from more than 20 institutions contributed, and the funders include the Novo Nordisk Foundation, the European Research Council and the Lundbeck Foundation.

Cardiolipin, the lipid that declines with age

The molecule is cardiolipin, which sits almost entirely in the inner membrane of mitochondria and helps hold its folded structure. According to the ScienceDaily report on the Copenhagen release, cardiolipin levels fell in muscle mitochondria from aging and diseased mice and from humans. The human evidence stops at that observation: people’s muscle samples showed the decline, and no human muscle was treated.

Mitochondria are the cell’s energy-producing compartments, and the folds of their inner membrane carry much of the machinery that does the work. When cardiolipin is scarce, that folded structure is compromised, which is the starting point for the cascade the Copenhagen team traced through reactive oxygen species and ERR gamma and into the identity of the muscle fibers themselves. The paper’s full title, “Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor gamma,” is listed under its Nature Aging DOI.

A switch that trades power for protection

When the team lowered cardiolipin in young mice, the animals developed changes resembling natural aging, including a move from fast-twitch to slow-twitch fibers. Low cardiolipin raised levels of reactive oxygen species, and those helped drive the switch, according to News-Medical’s account of the study. A protein called ERR gamma coordinates the response, and blocking it in cultured muscle cells stopped the transition. Cells in the low-cardiolipin mice also took up more glucose, which they appeared to use to build their own antioxidants.

Finger put the interpretation this way: the fiber switch is not the muscle failing, but the muscle trading power for protection. Slow, oxidative fibers cope better with the stress that low cardiolipin creates, at the cost of strength.

Fast-twitch fibers contract quickly and forcefully but tire sooner, while slow-twitch fibers generate less force and resist fatigue. Muscle that drifts toward the slow type loses peak power. The Copenhagen work frames that drift as a response with a purpose instead of a simple breakdown, and the team’s experiments suggest the oxidative stress produced by low cardiolipin is what pushes the fibers across, which is also why clearing that stress with antioxidants did not help.

Two-thirds of normal cardiolipin reversed the wasting in mice

Restoring cardiolipin to about two-thirds of its normal concentration reversed the muscle wasting and completely prevented the premature deaths seen in the affected animals, the Copenhagen release reports. Gerhart-Hines said he was most encouraged that even a partial recovery of cardiolipin was enough to bring the muscle back. The reachable reports give no lifespan figures or group sizes, so how large the survival effect was cannot be stated.

Several cautions follow from the design. The mice were engineered to lose cardiolipin, which the Fight Aging! summary notes may not fully reproduce natural aging, so repeating the work in old mice remains an open step. Giving mice antioxidants to clear the reactive oxygen species made their muscles fare worse, a sign that interfering with the protective switch can backfire, as Nautilus also reported.

The scale of the evidence is the main constraint. Mice live a few years while human muscle ages over decades, and a rescue that works after engineered cardiolipin loss may not carry over to the many other causes of muscle decline in people. The release gives no group sizes for the mouse experiments, and the human samples were used only to confirm that cardiolipin falls with age and disease. Nothing in the reports describes a person receiving a cardiolipin-raising treatment for muscle loss, and the researchers frame their next steps as questions rather than trials.

Related drugs exist for other conditions. The U.S. Food and Drug Administration granted accelerated approval to elamipretide, which helps stabilize cardiolipin, for Barth syndrome, a rare inherited disorder. Whether it does anything for ordinary age-related muscle loss is unknown, and drugs that activate ERR gamma are still in preclinical research for other uses.

The authors’ next questions, reported by Nautilus, are whether cardiolipin can be raised in aging muscle and whether ERR gamma can be targeted. Until those experiments are run, the finding is a mechanism seen in mice and a decline seen in human tissue, with a gap between them that only further trials can close.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

The day in tech, in one email: Get TLDR →

We may earn a commission if you sign up.