Genetic variant accelerates normal brain aging in older people by up to 12 years

March 15, 2017
Credit: CC0 Public Domain

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.

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 co-leader Asa Abeliovich, PhD, professor of pathology and neurology in the Taub Institute for Alzheimer's Disease and the Aging Brain at CUMC. "The same differences in aging can be seen in the , the region responsible for higher mental processes. Our findings show that many of these differences are tied to variants of a gene called TMEM106B. People who have two 'bad' copies of this gene have a frontal cortex that, by various biological measures, appears 12 years older that those who have two normal copies."

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 co-leader Herve Rhinn, PhD, assistant professor of pathology and cell biology in the Taub Institute. "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 . That got us thinking, 'What, on a genetic level, is driving healthy brain aging?'"

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 researchers found a second variant—inside the progranulin gene—that contributes to brain aging, though less so than TMEM106B. Progranulin and TMEM106B are located on different chromosomes but are involved in the same signaling pathway. Both have also been associated with a rare neurodegenerative disease called frontotemporal dementia.

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 . It's a vicious cycle."

The study is titled, "Genetic determinants of aging in human brain."

Explore further: Study points to possible cause of, and treatment for, non-familial Parkinson's

More information: "Genetic determinants of aging in human brain" Cell Systems, DOI: 10.1016/j.cels.2017.02.009

Related Stories

Study points to possible cause of, and treatment for, non-familial Parkinson's

February 6, 2013
Columbia University Medical Center (CUMC) researchers have identified a protein trafficking defect within brain cells that may underlie common non-familial forms of Parkinson's disease. The defect is at a point of convergence ...

Study reveals new link between Alzheimer's disease and healthy aging

August 15, 2011
Alzheimer's disease and frontotemporal lobar degeneration (FTLD) are two of the most prevalent forms of neurodegenerative disorders. In a study published online today in Genome Research, researchers have analyzed changes ...

Progranulin and dementia—a blood sample does not tell the full story!

May 26, 2016
Progranulin is a central protein in both neuronal survival and neurodegenerative diseases. It is thus not surprising that altered progranulin levels represent a universal theme shared across several common neurodegenerative ...

Glia, not neurons, are most affected by brain aging

January 10, 2017
The difference between an old brain and a young brain isn't so much the number of neurons but the presence and function of supporting cells called glia. In Cell Reports on January 10, researchers who examined postmortem brain ...

Getting closer to treatment for Parkinson's

January 23, 2017
More than 10 million people worldwide have Parkinson's disease. The cause of Parkinson's disease is unknown and thus no effective treatments exist. A study from the University of Bergen (UiB) suggests that the secret of the ...

Key molecular pathways leading to Alzheimer's identified

July 24, 2013
Key molecular pathways that ultimately lead to late-onset Alzheimer's disease, the most common form of the disorder, have been identified by researchers at Columbia University Medical Center (CUMC). The study, which used ...

Recommended for you

Newly revealed autism-related genes include genes involved in cancer

September 25, 2017
The identification of genes related to autism spectrum disorder (ASD) could help to better understand the disorder and develop new treatments. While scientists have found many genetic differences in different people with ...

Scientists first to use genetic engineering technique to investigate Tourette's

September 25, 2017
Scientists at Rutgers University-New Brunswick are the first to use a genetic engineering technique to create brain cells from the blood cells of individuals in a three-generation family with Tourette syndrome to help determine ...

Study reveals an ancient Achilles heel in the human genome

September 21, 2017
In a major study published today, researchers at deCODE genetics use whole-genome data from 14,000 people from across the population of Iceland, including 1500 sets of parents and children, to provide the most detailed portrait ...

Forgotten strands of DNA initiate the development of immune cells

September 21, 2017
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space.

Genome editing reveals role of gene important for human embryo development

September 20, 2017
Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human ...

A piece of the puzzle: Eight autism-related mutations in one gene

September 19, 2017
Scientists have identified a hotspot for autism-related mutations in a single gene.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.