How Aging Damages Memory

The results of a recent study into the origin of age-related memory impairment offer hope that this type of cognitive decline can be reversed (Science 2010, 328, 753).

Prior research suggested that gene expression employed by the brain for memory consolidation is partly controlled by acetylation of histones, the proteins around which DNA is wrapped. Other research indicated that gene expression in the brain is also affected by aging. In the new study, André Fischer, a neuroscientist at the European Neuroscience Institute, in Göttingen, Germany, and coworkers looked for evidence of a link between these two hypotheses.

Working with mice, the researchers found that aging reduces the animals’ ability to acetylate a lysine on the H4 histone, which hampers expression of genes involved in memory formation. Fischer's team also showed that injecting aging mice with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) increases acetylation of the H4 lysine and restores the learning ability of the mice.

J. David Sweatt, a neurobiologist at the University of Alabama, Birmingham, writes in a commentary about the work that "the study presents a major advance in thinking about the role of histone modifications in synaptic plasticity and memory formation." But he cautions against attributing "all of the memory disruption and pharmacological rescue effects in the aged animals to a single histone modification" (Science 2010, 328, 701).