Nav: Home

Brain-aging gene discovered

March 15, 2017

NEW YORK, NY (March 15, 2017) -- 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 frontal cortex, the brain 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 brain disease. 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 brain aging. It's a vicious cycle."
-end-
The study is titled, "Genetic determinants of aging in human brain."

The study was supported by grants from the National Institute of Aging (AG042317), the National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation for Parkinson's Research.

Dr. Abeliovich is a co-founder of and consultant for Alector. Dr. Rhinn is a consultant for Alector. The researchers declare no other financial conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.

The Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center and NewYork-Presbyterian Hospital brings together researchers and clinicians across disciplines to uncover the causes of Alzheimer's, Parkinson's, and other age-related brain diseases, and to discover ways to treat, prevent, and ultimately cure these diseases. In collaboration with the Departments of Pathology & Cell Biology and Neurology, research in the Taub Institute integrates genetic analysis, molecular and cellular studies, and clinical investigation to better understand complex neurodegenerative disorders. Funding for the Taub Institute's Alzheimer's Disease Research Center is provided by the NIH National Institute on Aging. In 2016, the Taub Institute was designated as a Center of Excellence for Alzheimer's Disease by the New York State Department of Health. For more information, visit The Taub Institute at http://www.cumc.columbia.edu/dept/taub/.

Columbia University Medical Center

Related Aging Articles:

The first roadmap for ovarian aging
Infertility likely stems from age-related decline of the ovaries, but the molecular mechanisms that lead to this decline have been unclear.
Researchers discover new cause of cell aging
New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works.
Deep Aging Clocks: The emergence of AI-based biomarkers of aging and longevity
The advent of deep biomarkers of aging, longevity and mortality presents a range of non-obvious applications.
Intelligence can link to health and aging
For over 100 years, scientists have sought to understand what links a person's general intelligence, health and aging.
Putting the brakes on aging
Salk Institute researchers have developed a new gene therapy to help decelerate the aging process.
New insights into the aging brain
A group of scientists at the Gladstone Institutes investigated why the choroid plexus contains so much more klotho than other brain regions.
We all want 'healthy aging,' but what is it, really? New report looks for answers
Led by Paul Mulhausen, MD, MHS, FACP, AGSF, colleagues from the American Geriatrics Society (AGS) set looking critically at what 'healthy aging' really means.
New insight into aging
Researchers at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University examined the effects of aging on neuroplasticity in the primary auditory cortex, the part of the brain that processes auditory information.
Aging may be as old as life itself
Aging has had a bad rap since it has long been considered a consequence of biology's concentrated effort on enhancing survival through reproductivity.
A new link between cancer and aging
Human lung cancer cells resist dying by controlling parts of the aging process, according to findings published online May 10th in the Journal of Biological Chemistry.
More Aging News and Aging Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.