Protein damage, radiation sensitivity and aging.

This paper promotes a concept that protein damage determines radiation resistance and underlies aging and age-related diseases. The first bottleneck in cell recovery from radiation damage is functional (proteome) rather than informational (DNA), since prokaryotic and eukaryotic cell death correlates with incurred protein, but not DNA, damage. Proteome protection against oxidative damage determines survival after ionizing or UV irradiation, since sufficient residual proteome activity is required to turn on the DNA damage response activating DNA repair and protein renewal processes. Extreme radiation and desiccation resistance of rare bacterial and animal species is accounted for by exceptional constitutive proteome protection against oxidative damage. After excessive radiation their well-protected proteome faithfully reconstitutes a transcription-competent genome from hundreds of DNA fragments. The observation that oxidative damage targeted selectively to cellular proteins results in aging-like phenotypes suggests that aging and age-related diseases could be phenotypic consequences of proteome damage patterns progressing with age.