This is a fascinating study at several different levels, and a very important contribution to our understanding of aging-related memory loss.

It builds significantly on a recent series of studies investigating both DNA methylation and histone acetylation in aging-related cognitive decline.

It also is an important contribution in the general area of understanding the role of neuro-epigenetic mechanisms in memory formation.

There are several key findings in the paper. First, the identification of Dnmt3a2 as an activity-regulated immediate early gene in the CNS. Second, identifying the critical role of Dnmt3a2 in memory in both young animals and in aging-related cognitive decline. Finally, this is a big step forward in beginning to understand the quite mysterious mechanisms that are involved in memory-associated DNA methylation.

View all comments by David Sweatt

This is very interesting. I am wondering how to relate those findings to the roles of folate in brain function and cognitive aging in humans.

Folate provides one carbon group to methylate DNA and other substrates. In population-based studies, low folate has been associated with poor cognitive performance, and trial results suggest that supplementation of folate and other B vitamins could slow down cognitive decline and brain atrophy. Optimizing folate status could be a potential preventive measure for dementia.

References:
Feng L, Ng TP, Chuah L, Niti M, Kua EH. Homocysteine, folate, and vitamin B-12 and cognitive performance in older Chinese adults: findings from the Singapore Longitudinal Ageing Study. Am J Clin Nutr. 2006 Dec;84(6):1506-12. Abstract

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007 Jan 20;369(9557):208-16. Abstract

Smith AD, Smith SM, de Jager CA, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley KM, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244. Abstract

Feng L. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline. Am J Clin Nutr. 2012 May;95(5):1289-90; author reply 1290. Abstract

View all comments by Lei Feng