Mitochondria-lysosome contacts (MLCs) are emerging as a dynamic membrane interface that integrates organelle communication with cellular homeostasis. Rather than acting solely as intermediates of degradative trafficking, MLCs organize local calcium transfer, lipid exchange, Rab7-dependent contact remodeling, and mitochondrial quality control. These functions place MLCs at the intersection of mitochondrial fitness, lysosomal competence, metabolic adaptation, and stress signaling. Aging provides a particularly informative setting in which to examine this interface, because mitochondrial dysfunction and lysosomal decline co-emerge and reinforce one another during cellular aging. Current evidence suggests that aging does not simply increase or decrease MLCs, but instead remodels their dynamics, molecular composition, and functional output. Such remodeling may impair mitophagy, alter calcium and lipid coupling, amplify oxidative and inflammatory stress, and contribute to age-related disease phenotypes. In this review, we summarize the structural organization and regulatory logic of MLCs, examine their mechanistic roles in organelle homeostasis, and discuss how aging reshapes this interface in physiological and pathological contexts. We also highlight key methodological challenges and therapeutic opportunities for the field.
