Cardiolipin Loss Linked to Age-Related Muscle Decline in Mice

Aging muscles shift toward slow-twitch fibers and lose cardiolipin, a mitochondrial fat needed for energy production and membrane structure. In mice and cultured muscle cells, reducing cardiolipin reproduced this fiber shift, and glucose was redirected toward making antioxidants instead of being burned for fuel. Restoring part of the depleted mitochondrial fat partially reversed muscle wasting in mice, pointing to a possible treatment strategy for age-related muscle weakness.

Cardiolipin is a lipid concentrated in the mitochondrial inner membrane, where it helps preserve the folds required for energy production and metabolic signaling. In aging and muscle disease, its abundance drops, and mitochondria become misshapen and inefficient. Human muscle biopsies show the same age-related decline.

In young mice, experimentally lowering cardiolipin triggered a fast-to-slow fiber transition resembling old muscle. These fibers consumed more blood glucose, but used it to build antioxidants rather than fuel. Reactive oxygen species helped initiate this remodeling via ERRγ; antioxidant treatment interfered with the adaptation. Partial cardiolipin restoration reduced wasting and prevented premature death.