Helicases and aging

Studying monogenic hereditary disorders that manifest age-related phenotype s in cells, tissues, and the total organism would be helpful for clarifying the mechanisms of aging. In this context, seven human disorders that manif est age-related phenotypes have been found to be caused by aberrations of f ive proteins with seven helicase motifs conserved in most of the helicases. These disorders are xeroderma pigmentosum, Cockayne syndrome, trichothiody strophy, Bloom syndrome, Werner syndrome, X-linked alpha-thalassemia/mental retardation syndrome, and Juberg-Marsidi syndrome. A decline of probably p leiotropic and fundamental function of helicases in these disorders is, the refore, implied to underlie not only the various age-related phenotypes of the disorders but also the pleiotropic and universal nature of ordinary agi ng. Consistent with this implication, studies of these seven disorders sugg est that their various age-related phenotypes are caused by aberrations in multiple processes, especially transcription. Furthermore, a few studies im ply some association between aberration of the helicases and phenotypes in ordinary aging.