Our actual age can differ from the age our brain appears to be
Julien Tromeur / Alamy
Seven genes have been linked to particularly fast ageing of the brain – but 13 drugs and supplements might reduce their effects.
The activity of many genes contributes to the difference between our actual age and the biological age of our brains, defined by how old our cells indicate we are, which creates what is known as a brain age gap.
To find genes that accelerate brain ageing and widen this gap, Zhengxing Huang at Zhejiang University in China and his colleagues trained a deep-learning model called 3D-ViT on some medical records and used others to check it gave accurate responses.
They then used it to analyse data from nearly 39,000 people who had health, genetic and lifestyle information, along with biological samples, stored in the UK Biobank. These participants were 64 years old, on average, and about half were women.
3D-ViT identified signatures in the participants’ MRI scans that could be used to estimate their biological brain age. Signs of accelerated ageing particularly appeared in brain regions known as the lentiform nucleus, which is involved in cognition, such as attention and working memory, and the posterior limb of the internal capsule, which connects various regions to the brain’s cerebral cortex – used for thought and language processing.
Huang and his colleagues also found that the participants’ scores on cognition tests dropped as their brain age gap increased.
Comparing their gene variants with the size of their estimated brain gaps flagged 64 influential genes, but Huang and his colleagues focused on seven: MAPT, TNFSF12, GZMB, SIRPB1, GNLY, NMB and C1RL, partly because these all have a particularly strong effect on brain ageing.
Clinical trials have also shown that their activity can be targeted by 13 drugs or supplements. These include cholecalciferol, a supplement for vitamin D deficiency; dasatinib, a leukaemia drug; diclofenac, a non-steroidal anti-inflammatory; doconexent, an omega-3 fatty acid; estradiol, the type of oestrogen commonly used in hormone replacement therapy; hydrocortisone, commonly used to treat eczema; and mecamylamine, a drug that lowers blood pressure.
The others were nicotine; prasterone, which relieves vaginal pain during sex during the menopause; the supplements quercetin and resveratrol; sirolimus, which is commonly used to suppress the immune system after a kidney transplant; and testosterone.
But the researchers write that 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”.
Many genes have an effect on brain ageing, but here the authors have used an approach that prioritises those with the largest effect, says Dario Valenzano at the Leibniz Institute on Aging in Jena, Germany. “The work provides concrete targets for direct follow-up experimental and clinical interventions.”
But it is hard to tell how large an effect on brain ageing these genes actually have, says Richard Siow at King’s College London. “Just because you have a certain genetic profile doesn’t mean the genes will always play a role.”
Genes can be silenced or switched on by various lifestyle and environmental factors, he says, such as smoking and high alcohol consumption. These can also predispose people to cognitive decline or brain ageing.
Because the study used data in the UK Biobank, we don’t know whether the findings translate to people around the world, says Siow. Work is needed in other populations, such as those in Africa, South America and East Asia, to find that out, he says.
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