Iterations in the rate and extent of protein synthesis, accuracy, post-translational modifications and turnover are among the main molecular characteristics of aging. A decline in the cellular capacity through proteasomal and lysosomal pathways to recognize and preferentially degrade damaged proteins leads to the accumulation of abnormal proteins during aging. The consequent increase in molecular heterogeneity and impaired functioning of proteins is the basis of several age-related pathologies, such as cataracts, sarcopenia and neurodegerative diseases. Understanding the proteomic spectrum and its functional implications during aging can facilitate developing effective means of intervention, prevention and therapy of aging and age-related diseases.