Restoring One Muscle Fat Prevented Early Death in Adult Mice
Take one fat molecule out of a mouse’s muscles, and the animal withers: smaller muscles, a weaker grip, an early death. Let the body make that molecule again, and the damage starts to heal. In a new study in Nature Aging, the wasting began to reverse in adult mice, and the premature deaths were prevented. Cardiolipin, the fat in question, sits inside mitochondria, the power plants of the cell, and its levels fall in aging muscle, in both mice and a small group of people.
That makes it a suspect in one of aging’s most familiar frustrations, the slow loss of strength. Climbing stairs, hauling groceries and catching a stumble all lean on fast-twitch fibers, the type that tends to fade first. Aging muscle shrinks, but it also trades fast, powerful fibers for slower, endurance-type ones. Scientists have found that swap puzzling, because the slower fibers lean even harder on the power plants that wear down with age.
Researchers at the University of Copenhagen and collaborators found that stripping cardiolipin from young mice made their muscles look aged. The cause-and-effect work was done in mice and lab-grown mouse cells.
Cardiolipin Falls With Age in Mouse and Human Muscle
Muscle fibers come in two broad types: fast-twitch for bursts of power, like jumping, and slow-twitch for stamina, like a long walk. As people age, fast-twitch fibers tend to shrink while slow-twitch ones become relatively more common. Cardiolipin is a minor fat, but it helps hold the power plants inside those fibers together.
To look for a decline, researchers compared 9-week-old mice with 2-year-old mice. Older animals had less cardiolipin in both fast and slow muscle, and less activity in the gene that builds it. Muscle samples from four adults aged 22 to 35 and five aged 53 to 69, saved from an earlier exercise study, showed a similar drop.
A drop alone does not prove cause, so the team engineered mice that lose that gene only in skeletal muscle. Some lacked it from birth. In others, a drug switched the gene off in adulthood, and stopping the drug let production recover. Both male and female mice were used in the main experiments, with fewer than a dozen animals per group in most comparisons.
Removing Cardiolipin in Young Mice Mimicked Aging Muscle
Mice without muscle cardiolipin gained less weight after weaning, entirely because they built less lean mass. Their body fat and activity levels matched normal mice, so inactivity did not explain the weak muscles. Fast-twitch muscle shrank the most, its fibers growing smaller rather than dying, and the remaining fibers tilted toward slower types, mirroring what happens in older people. Inside the cells, the power plants looked disorganized and had less capacity to make energy. Adult mice whose gene was switched off lost grip strength within five weeks, measured by how hard they resisted a gentle backward tug.
A signaling protein that carries messages from the power plants to the cell’s nucleus ramped up in fast-twitch muscle. In lab-grown muscle cells, blocking it prevented the shift toward slower fibers, showing the protein was required for the change, not a bystander.
Metabolism shifted too. The mice burned more fat and cleared blood sugar faster. Their muscles steered sugar into side routes that fuel antioxidant defenses against the damaging molecules that stressed power plants release. Giving the mice an antioxidant supplement called NAC for eight weeks backfired, and muscle loss got worse. The authors caution that the picture is unsettled, since high doses of NAC can interfere with insulin signaling.
Source : https://studyfinds.com/fading-muscle-fat-may-explain-strength-slips-age/
