Columbia University Medical Center (CUMC) researchers have discovered a common genetic variant that greatly impacts normal brain aging, starting at around age 65, and may modify the risk for neurodegenerative diseases. The findings could point toward a novel biomarker for the evaluation of
The study was published online today in the journal Cell Systems.
«If you look at a group of seniors, some will look older than their peers and some will look younger," said the study’s
Studies have identified individual genes that increase one’s risk for various neurodegenerative disorders, such as apolipoprotein E (APOE) for Alzheimer’s disease. «But those genes explain only a small part of these diseases," said study
In the current study, Drs. Abeliovich and Rhinn analyzed genetic data from autopsied human brain samples taken from 1,904 people without neurodegenerative disease. First, the researchers looked at the subjects’ transcriptomes (the initial products of gene expression), compiling an average picture of the brain biology of people at a given age. Next, each person’s transcriptome was compared with the average transcriptome of people at the same age, looking specifically at about 100 genes whose expression was found to increase or decrease with aging. From this comparison, the researchers derived a measure that they call differential aging, the difference between an individual’s apparent (biological) age and his or her true (chronological) age. «This told us whether an individual’s frontal cortex looked older or younger than expected," said Dr. Abeliovich.
The researchers then searched the genome of each individual, looking for genetic variants that were associated with an increase in differential age.
«One variant stood out: TMEM106B," said Dr. Rhinn. «It’s very common. About
«TMEM106B begins to exert its effect once people reach age 65," said Dr. Abeliovich. «Until then, everybody’s in the same boat, and then there’s some yet-
The researchers found a second
The study did not address what role the two genetic variants might have in neurodegenerative disease. «We were studying healthy individuals, so it is not about disease, per se," said Dr. Abeliovich. «But of course, it’s in healthy tissue that you start to get disease. It appears that if you have these genetic variants, brain aging accelerates and that increases vulnerability to brain disease. And vice versa: if you have brain disease, the disease accelerates brain aging. It’s a vicious cycle.»
The study is titled «Genetic determinants of aging in human brain.»
The study was supported by grants from the National Institute on Aging (AG042317), the National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation for Parkinson’s Research.
Dr. Abeliovich is a
Source: http://newsroom.cumc.columbia.edu/blog/2017/03/15/brain-aging-gene-discovered/