Tuesday, June 01, 2010

Epigenetics and cognitive aging

Even in my genteel retirement, I read Science and Nature every week. Or, at least, I browse the stories, even those I don't fully understand. One can generally sop up a sense of what's going on.

Consider the following abstract of an article called "Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice":
As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.
The key words here are histone and acetylation, so I provide Wikipedia links, but there's no need to dig into the biochemistry. What we are talking about here is gene expression, and its declining effectiveness with age. Our researchers worked with three groups of mice, ages 3, 8 and 16 months (average lifetime, 27 months). The older mice had a harder time remembering their way through the maze.

Those of you in my age cohort will relate.

This mousal memory deficit correlates with a decline of histone acetylation, as illustrated by this lovely little diagram. I like the look of that DNA wound up on those histone bobbins with the acetyl groups happily hanging on. Isn't it wonderful that something so pretty on a sub-microscopic scale may determine whether or not I remember my wife's birthday or where I put the car keys.

What works for mice may or may not work for humans, but our researchers were able to restore memory function in those not-quite-tottering 16-month-old mice with a intrahippocampal infusion of suberoylanilide hydroxamic acid (don't try this at home). You can be sure memory pills will be in the works for humans in the not too distant future. Alas, not soon enough for me.

There was something else I wanted to add. Now what was it?

(Illustration credit: C. Bickel, Science.)