Chromatin and epigenetic dynamics in senescence phenotypes - John Sedivy
Chromatin is a complex and dynamic structure that needs to be maintained in a functional state throughout the lifetime of an organism. Studies of diverse species, including mammals, have revealed that chromatin undergoes extensive rearrangements during aging. Cellular senescence, an important component of mammalian aging, has recently been associated with decreased heterochromatinization of normally silenced regions of the genome. These changes appear to lead to the expression of retrotransposable elements (RTE), culminating in their transposition. RTEs are common in all kingdoms of life, and comprise close to 50% of mammalian genomes. They are tightly controlled, as their activity is highly destabilizing and mutagenic to the genomes in which they reside. In my presentation I will develop the hypothesis that the "loosening" of our endogenous genomic parasites, the RTEs, is an important and hitherto unexplored molecular aging process that can potentially occur in most of our tissues. We further envision that the activation and continued presence of retrotransposition contributes to age-associated tissue degeneration and pathology.