Epigenetics has become an important component of the study of aging: how genetic regulation changes in response to cellular and molecular damage. One of the mechanisms of this regulation is the acetylation of histones: researchers evaluate the way in which this changes with aging, leading to changes in gene expression, altered levels of key protein machinery in tissues, and changes in the operation of biological systems in the body. Some research groups are in search of epigenetic alterations that might be reversed through therapy to produce beneficial effects:
Aging increases the vulnerability of aging white matter to ischemic injury. Histone deacetylase (HDAC) inhibitors preserve young adult white matter structure and function during ischemia by conserving ATP and reducing excitotoxicity.
In isolated optic nerve from 12-month-old mice, deprived of oxygen and glucose, we show that pan- and Class I-specific HDAC inhibitors promote functional recovery of axons. This protection correlates with preservation of axonal mitochondria. The cellular expression of HDAC 3 in the central nervous system (CNS), and HDAC 2 in optic nerve considerably changed with age, expanding to more cytoplasmic domains from nuclear compartments, suggesting that changes in glial cell protein acetylation may confer protection to aging axons.
Our results indicate that manipulation of HDAC activities in glial cells may have a universal potential for stroke therapy across age groups.