Vacuolar H(+)-ATPase Preserves Cardiolipin Homeostasis Through the Lysosomal-Mitochondrial Axis to Restrain Cardiac Aging.

Vacuolar H(+)-ATPase dysfunction causes cardiolipin depletion and mitochondrial failure, driving age-related cardiomyopathy in mice and humans.

• Why it matters: Understanding how lysosomal and mitochondrial interactions deteriorate with age is crucial for developing therapies against cardiac aging and failure.
• What they did: The study used RNA sequencing, lipidomics, microscopy, and mouse models, including knockout and nutraceutical interventions, to investigate v-ATPase's role in cardiolipin homeostasis during aging.
• The result: Restoring NAD+ levels improved lysosomal function and cardiolipin metabolism, preventing cardiac decline, and suggesting that enhancing v-ATPase activity could be a promising treatment for age-related heart disease.