Researchers identified 64 genes that help to shape how quickly a person's brain ages, which could explain the gap often observed between the estimated biological age and the chronological age of the brain, according to a new study published in the journal Science Advances. The study also highlighted 13 drugs and supplements that can be repurposed to slow down brain aging, including those already tested or currently being tested in anti-aging clinical trials.
The research, led by Fan Yi from Zhejiang University in Hangzhou, China, is one of the largest efforts to pinpoint genetic factors influencing brain decline. Based on analyses of brain scans and biological samples from approximately 39,000 individuals in the UK Biobank, the team aimed to better understand and find new ways to slow brain aging.
Using a deep-learning model trained to estimate brain age called 3D-ViT, the scientists analyzed medical records to find genes that accelerate brain aging. By calculating the difference between each person's predicted brain age and their chronological age, known as the brain age gap (BAG), they identified 64 genes associated with brain aging. The BAG is a reliable biomarker for studying brain health, representing the difference between a person's estimated biological brain age and their actual age.
Among these genes, seven—MAPT, TNFSF12, GZMB, SIRPB1, GNLY, NMB, and C1RL—related to blood coagulation and cell death, had the strongest association with the brain age gap. The researchers found that these genes are promising targets for slowing brain aging and could represent new targets for developing drugs against brain aging.
The team also discovered 466 compounds, either approved as drugs or being tested in clinical studies, that target 29 of these genes and could help to reverse brain aging. Thirteen of these compounds were already tested or are being tested in anti-aging clinical trials. Some of the drugs identified include hydrocortisone, testosterone, diclofenac, metformin, and rapamycin, the latter of which is currently in a trial for slowing ovarian aging.
"The findings are significant because they could pave the way for new treatments to keep the brain healthier longer," said neuroscientist Agustín Ibáñez from Trinity College Dublin. However, he added, "There is still much work to be done before these discoveries can have practical application." Experimental studies will be needed to test whether the proposed drugs can slow brain aging.
The authors of the study cautioned that the effectiveness of these drugs in slowing brain aging requires further confirmation. "People should be encouraged to consider the potential risks associated with taking medications or supplements for slowing down aging as these interventions may have unintended negative consequences," the researchers wrote.
Professor Richard Siow at King's College London noted that genes can be silenced or switched on by various lifestyle and environmental factors such as smoking and high alcohol consumption, which can also predispose people to cognitive decline or brain aging. He also pointed out that it is hard to tell how large an effect on brain aging these genes actually have.
The team performed analyses on a subset of 31,520 healthy participants with genetic data available, primarily from European populations, raising questions about the applicability of the findings to more genetically diverse groups. "It is unclear whether the findings apply to more genetically diverse groups," Ibáñez said.
A larger brain age gap is linked to lower cognitive test scores and increases the risk of developing cognitive disorders and neurological diseases. Brain aging impacts overall human aging and contributes to the decline in both physical and cognitive health. Slowing the aging process is a powerful strategy to prevent many diseases and enhance longevity.
Brain regions critical for brain age estimation included the lentiform nucleus and the posterior limb of the internal capsule, which are involved in cognition, attention, and working memory, and connect various regions of the brain to the cerebral cortex. These findings indicate the importance of these brain regions in the aging process.
"Many genes have an effect on brain aging, but here the authors have used an approach that prioritizes those with the largest effect," said Dario Valenzano at the Leibniz Institute on Aging in Jena, Germany. He added, "The work provides concrete targets for direct follow-up experimental and clinical interventions."
The article was written with the assistance of a news analysis system.