Common genetic changes linked to faster brain ageing

15 March 2017

Cell Systems: Differential Aging Analysis in Human Cerebral Cortex Identifies Variants in TMEM106B and GRN that Regulate Aging Phenotypes

US researchers have discovered that a small change in the DNA code of two genes is associated with a faster than normal rate of brain ageing. The findings help to inform research into the mechanisms behind healthy ageing. The study is published on 14 March in the journal Cell Systems.

With an increasingly ageing population in the UK and worldwide, there is a growing need to understand the mechanisms influencing brain health into older age. Age is the biggest risk factor for diseases like Alzheimer’s, but there are also broad differences in how well people age within the healthy population. Researchers at Columbia University Medical Center set out to understand the factors underlying this natural variation in the rate of normal brain ageing.

The team used brain tissue taken from autopsies of 1,904 people without any neurodegenerative diseases and carried out extensive genetic analysis of the DNA code of the individuals.

They first studied the expression of genes in an area of the brain called the frontal cortex and developed a system of mapping that expression against age for the group to create a benchmark. They could then calculate whether each individual was ageing faster or more slowly than would be expected for their age, compared to the scores from the whole group.

By studying the genetic code of individuals who appeared to be ageing more quickly than expected, the team identified changes in two genes called TMEM106B and progranulin that were more strongly associated with faster ageing in people over 65. TMEM106B was shown to be associated with the expression of genes involved in inflammation, and both TMEM106B and progranulin have previously been linked to dementia.

Dr David Reynolds, Chief Scientific Officer of Alzheimer’s Research UK, said:

“By 2040, nearly one in seven people in the UK will be over 75 so there is a pressing need to understand the biological mechanisms that separate those who age well from those who don’t. How well a person ages can’t be defined by a single factor, but is likely to be made up of many contributing elements shaped throughout a person’s life. We know that natural variation in our genes can influence many aspects of our lives, including our risk of diseases like Alzheimer’s, so it’s not surprising to see them influencing healthy ageing too.

“While this study only focused on one region of the brain, piecing together these genetic clues can help build a clearer understanding of biological processes most susceptible to decline as we get older. Although this was not a study about dementia, it’s interesting that the two genes identified have also been linked to a form of the condition. Inflammation is an area of growing interest in dementia research and this study suggests that changes in a person’s immune response in later life may be an important determinant of healthy ageing as well as disease. As age is the biggest risk factor for dementia, unravelling the factors influencing healthy ageing can also help us better understand what goes wrong in brain diseases like Alzheimer’s.”