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 anti-aging interventions and highlight potential new targets for the prevention or treatment of age-associated brain disorders such as Alzheimer's disease.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 to 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 one-third of people have two copies and another third have one copy."
"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-to-be-defined stress that kicks in.
If you have two good copies of the gene, you respond well to that stress. If you have two bad copies, your brain ages quickly." The study has been published in the journal Cell Systems.
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