Oxidative damage affects protein structure and function. Progressive accumulation of oxidized proteins is considered a putative mechanism of aging; however, empirical evidence supporting their role in aging is inconsistent. This inconsistency may reflect a failure to distinguish damage to particular cellular compartments. We found a significant reduction of protein carbonyls in the insoluble, but not in the soluble, fraction of liver tissues of long-lived compared with their short-lived counterpart. Of cellular components analyzed, only nuclear protein carbonyl level was uniformly reduced in long-lived compared with short-lived animals. This observation suggests that attenuated accumulation of protein carbonyls in the nucleus, where they can affect multiple aspects of gene expression and DNA repair, might contribute to the longevity in mammalian species. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.