Ever feel like you’re forgetting things more often as you get older? Little things like where you put your keys or why you walked into the cold room (not that we would know what that’s like – as far as you know!) can turn into huge mysteries. Researchers now think they’ve pin-pointed why this happens, and it has to do with H4K12 acetylation – or the lack of it.
The team noticed that 16-month-old mice didn’t learn as quickly as their younger counterparts when they were put through learning tests. As we reported in March, histone methylation seems to be involved in memory formation, but this team decided to look at whether histone acetylation was different in the hippocampuses of 16-month-old (old) mice versus 3-month-old (young) mice. Here are a few of their observations:
- Shortly after a learning test, young mice had increased acetylation on H3K9, H3K14, H4K5, H4K8, and H4K12. The old mice had a similar histone mod profile, except that H4K12 acetylation wasn’t up-regulated.
- The young mice also up- or down-regulated the expression of 2229 genes (most were linked to learning), but the expression of only 6 genes changed in old mice.
- With ChIP-seq, the researchers found that H4K12 acetylation was impaired in old mice around the transcription start site and within coding regions of genes that were up-regulated in young mice.
- And now, the way-cool part: when the scientists injected old mice with an HDAC inhibitor (SAHA or sodium butyrate), they reversed the aging effects—H4K12 acetylation went up, the expression of learning genes increased, and the old mice seemed to learn better!
Who says you can’t teach old mice new tricks? Hold on though before you go injecting yourself with SAHA, and read the details first at Science, May 2010.