Most neurons remain in a non-diving state over an animal’s lifetime. A subset of neuronal proteins persist throughout adulthood exhibiting age-dependent decline. It is unclear if extreme longevity of cells and proteins affects aging of other organs. We discovered cells and proteins with exceptional lifespans in rodent brain, liver and pancreas. Besides neurons, major cell types such as endothelial cells, hepatocytes and major pancreatic cells are mostly as old as the organism. Using nuclear pore complexes (NPCs) as a paradigm for long-term protein persistence, we describe two distinct NPC maintenance mechanisms in quiescent and post-mitotic cells: NPC removal from intact nuclei and piecemeal replacement, respectively. Strikingly, human beta cells exhibit age-dependent loss of NPC components and defects in nuclear integrity similar to old neurons. Our findings link long-lived cells and proteins to the aging process and reveal age mosaicism as a principle of adult tissue and protein homeostasis.