Genetic variant can speed brain aging by up to 12 years

old man
A genetic variant, which can accelerate brain aging in people over 65, could lead the way to new targets for drugs treating age-associated disorders.

It isn’t exactly breaking news that people of the same age can look older or younger than each other—but it turns out their brains do the same. Columbia University researchers have identified a genetic variant that can hasten brain aging up to 12 years in some people.

While their research does not specifically target neurodegenerative diseases, such as Alzheimer’s, the discovery could lead to a new biomarker for assessing anti-aging treatments, as well as new targets for drugs to treat age-related disorders.

The team found the variant by looking at nearly 2,000 brain samples from autopsies of older people who did not have a neurodegenerative disease, according to a statement. They examined each subject’s transcriptome—the initial products of gene expression—and compared them against the average transcriptome for people of the same age. They were looking specifically for genetic variants linked to an increased "differential" age, a measure they created that describes the difference between an individual’s chronological age and his or her biological age.


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“One variant stood out: TMEM106B," said Herve Rhinn, a study co-leader and an assistant professor of pathology and cell biology at Columbia’s Taub Institute for Alzheimer’s disease and the Aging Brain, in the statement. "It's very common. About one-third of people have two [bad] copies and another third have one copy."

People who have two faulty copies of this gene have a frontal cortex that appears 12 years older than that of a person with two normal copies, said Asa Abelioivich, a professor of pathology and neurology at the Taub Institute and a co-leader of the study. This frontal cortex is responsible for higher mental processes, including memory, thinking and emotion.

Several research groups are pursuing different strategies for examining the aging brain.

In 2015, for example, startup startup NeuroVigil teamed up with the the American Senior Housing Association to arm 20,000 seniors with wearable brain monitors that record age-related changes, as well as changes related to dietary choices and other lifestyle factors. And last year, scientists at UCLA used a miniature microscope to identify, in mice, methods by which the brain links memories over time, and to examine what happens to those connections over time.

But linking genes to aging remains a priority, and the Columbia researchers believe their latest discovery will be a valuable addition to that effort. TMEM106B begins to affect brain aging around age 65, the researchers said, and it may alter an individual’s risk for disorders such as Alzheimer’s.

While previous research has pinpointed certain genes that raise one’s risk of these disorders, Rhinn said aging plays a bigger role in determining risk. "By far, the major risk factor for neurodegenerative disease is aging. Something changes in the brain as you age that makes you more susceptible to brain disease,” he said.

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