Molecular chaperones dampen the effect of damaging mutations that would otherwise be removed from the population by natural selection. Here, I propose that the development of modern medical practice depressed this process, leading to a rise of phenotypically silent mutations in the genome. The background of misfolded proteins increases during ageing and, by competition, prevents the chaperone-mediated buffering of silent mutations. Phenotypically exposed mutations contribute to a more-abundant manifestation of multigene-diseases. This 'chaperone overload' hypothesis emphasizes the need for efficient ways to enhance chaperone capacity in ageing subjects, and will hopefully lead to the identification and 'repair' of silent mutations.
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