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New research uses the study of epigenetics, the study of gene expression, to uncover a link between aging and gene expression in Alzheimer’s disease.
Aging is the greatest risk factor for Alzheimer’s disease and is the most common cause of dementia in elderly people. Changes in specific genes may increase the risk of Alzheimer’s disease. However, very little is known about how the molecular processes of aging drive the development of Alzheimer’s disease.
Researchers from the University of Pennsylvania studied changes in epigenetics and how they affect aging and Alzheimer’s disease. In a nutshell, the term epigenetics refers to the study of the biological mechanisms that turn genes on or off. One such mechanism involves changes to histones, or proteins that interact with our DNA to drive gene expression.
In a study published in Nature Neuroscience, the researchers examined a specific histone modification called H4K16ac. Previous studies suggest that this histone modification may be involved in the aging of the brain.
Using postmortem brain tissue samples from the Center for Neurodegenerative Disease Research, investigators studied the enrichment and distribution of H4K16ac in brain tissue from “old” subjects who were cognitively normal, with an average age of 68 years, “young” subjects who were cognitively normal, with an average age of 52 years, and “Alzheimer’s disease” subjects who were aged around 68 years.
Epigenetics show that Alzheimer’s is not the amplification of aging
The study found that both aging and Alzheimer’s disease were associated with changes in H4K16ac. However, an overall increase in H4K16ac was observed with normal aging while an overall loss of H4K16ac was seen in subjects with Alzheimer’s disease. Additionally, some of the H4K16ac changes in Alzheimer’s disease subjects were the opposite of those seen in normal aging. This is contrary to the natural assumption that cognitive decline is the result of an amplification of the natural aging process. In this case there is, instead, a dysregulation of the expression of applicable genes. The represents a novel target for Alzheimer’s treatment and prevention.
The results of this study are important because they suggest that epigenetics influence the changes associated with normal aging which may protect against Alzheimer’s disease. Researchers hope that this protective aspect has the capacity to be enhanced.
Written by: Cindi A. Hoover, Ph.D.
(1) Nativio R, Donahue G, Berson A, et al. Dysregulation of the epigenetic landscape of normal aging in Alzheimer’s disease. Nat Neurosci. 2018. doi:10.1038/s41593-018-0101-9.
(2) Fyfe I. Epigenetics links ageing with Alzheimer disease. Nat Rev Neurol. 2018. doi:10.1038/nrneurol.2018.36