Investigating the Role of Epigenetic Dysregulation in Mammalian Aging
2011 new Scholar Award in aging
Physiological aging is characterized by a complex set of cellular changes, including epigenetic alterations. Epigenetic mechanisms ensure that descendant cells inherit the identity of their predecessors, by marking the genome in a manner that persists through cell division. Importantly, epigenetic inheritance is not hard-wired into our DNA; it is subject to change. Epigenetic changes are in fact hypothesized to be one contributor to physiological aging and to age-related diseases.
We propose to exploit the reversal of X-chromosome inactivation, a paradigm of stable epigenetic inheritance, to assess the impact of epigenetic dysregulation on aging. The proposed work will determine the extent to which epigenetic dysregulation is a component of normal aging and whether it is a cause or consequence of aging. We propose to establish an experimental system where the cellular epigenetic machinery is manipulated to alter aging-associated epigenetic plasticity.