THE ARISING · Longevity & Healthspan
Falling Cardiolipin Levels May Explain Why Aging Muscles Lose Power
Aging muscle has a puzzle at its core: as mitochondria, the cell's energy units, work less well, muscle shifts toward fibers that rely on them more. A new study in Nature Aging suggests a single fat in the mitochondrial membrane, called cardiolipin, may explain why.
The evidence comes mainly from mice, with some work in human muscle. It is a peer-reviewed paper published in 2026 by a large team, led by Fabian Finger and Zachary Gerhart-Hines at the University of Copenhagen, according to Earth.com's coverage.
Aging brings two changes that seem to conflict. Mitochondrial function in skeletal muscle declines. Yet muscle composition shifts toward fibers rich in mitochondria. The authors report that cardiolipin links the two. Its levels fall in aging mouse and human muscle.
To test cause, the researchers lowered cardiolipin in young mice. They deleted a gene called Crls1, which makes an enzyme needed to build the fat, only in muscle and only on cue. This reproduced key hallmarks of aging, including a shift from glycolytic fibers to oxidative ones. Glycolytic fibers burn sugar quickly. Earth.com describes them as the fast, powerful fibers.
The study also describes how the shift happens. Mitochondria send a signal to the cell nucleus through a protein called estrogen-related receptor γ. That signal promotes sugar uptake that is sensitive to reactive oxygen species, which are damaging byproducts of energy production. It also reroutes sugar to support the cell's antioxidant defenses.
Some of the damage was also reversible in the mice. When the authors restored Crls1 in adult mice that had lost it, cardiolipin levels returned, muscle atrophy began to reverse and premature death was fully rescued.
Cardiolipin-depleted mice given the antioxidant N-acetylcysteine for eight weeks ended up with smaller muscles, not healthier ones. Finger told Earth.com: "The fiber switch is not the muscle failing, but the muscle trading power for protection." Earth.com says these groups were small, with three to six mice each.
That is the basis for the question many readers will ask about antioxidant pills. The study does not answer it. The mice had been engineered to lack cardiolipin, and the study did not test supplements in older people. Earth.com also notes that the human data were limited to stored muscle samples from nine men, which showed only that cardiolipin was lower with age.
The same goes for exercise. What the study does suggest is that the loss of powerful fibers may have a specific biological cause. That makes the cause a possible target for future treatments. It is not yet a guide to what anyone should do.
Earth.com reports that the authors' next step is to raise cardiolipin in naturally old mice and see whether that protects their muscles. That result will show whether this pathway matters beyond a model of early muscle aging.
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