Many proteins and nucleic acids can self-assemble into condensates with diverse material properties. Yet the breadth and implications of this behavior remain elusive across the lifespan. Aberrations in assembly properties can drive the spread of disease pathology within and, in extreme cases, between individuals. Yet how self-assembly differs in youth, age, and disease remains poorly understood, especially in vertebrates. Using ligand-controllable degrons, we created a versatile reporter system to quantify self-assembly and its transmissibility on a proteome-wide scale. Remarkably, both properties were widespread across all domains of life. In the human proteome, self-assembly was strongly enriched among proteins pivotal for early development, stress responses, and intercellular communication. Disease-associated mutations, particularly those linked to neurodegenerative disorders and cancer, frequently altered condensation and templating behaviors, suggesting a direct link to pathogenesis. Using both machine learning and biochemical reconstitution, we leveraged this large dataset to identify new molecular determinants of protein self-assembly into liquids, gels, and solids, as well as their capacity for prion-like templating over long biological timescales. Finally, employing the African turquoise killifish – a model vertebrate with a compressed lifespan – we extended our proteomic analysis to reveal parallels in aging tissues. With advancing age, the prion-like assembly of specific proteins increased substantially. In the same aged tissues, the molecular chaperones that act on these proteins also aggregated concomitantly, highlighting a negative feedback loop that may further impair proteostasis and intensify aggregation. Indeed, a segmental progeria model exhibited increased aggregation only in tissues with signatures of accelerated aging. Collectively, these lines of evidence establish that protein self-assembly and self-templating are far more common in vertebrate proteomes than previously appreciated and suggest that their advantages in youth may be inseparable from costs in aging and disease.