Cellular and molecular interfaces connect functional and structural units in biological systems. They represent modules of communication between proteins, cells, tissues and organs, and at which decisions are initiated and information is passed on. Synapses or the stem-cell niche interface are examples of such interfaces. Interfaces are therefore primary regulatory hubs of multicellular organisms. Dysregulated interfaces contribute to the loss of cellular and molecular homeostasis. We hypothesize that aging-related tissue decay as well as aging-related diseases are a result of changes in both the quality and quantity of the interactions at interfaces. Such changes may be: i) protein misfolding that modulate interactions with other proteins, ii) one affected cell influencing its surrounding cells and/or iii) an aging phenotype of one tissue being conferred to another tissue.