To Understand a Brain’s Age, Focus on More Than Neurons

Photo: Sally Anscombe/Getty Images

Neurons have long had a starring role in the study of the brain and its diseases. But just as every Frodo Baggins needs a Samwise Gamgee, neurons just aren’t who they are without glia, the brain cells that nourish, insulate, and protect them.

According to a just-published study in Cell Reports, it’s the glia, those best actors in a supporting role, that show major changes in the brain as people get older. Jernej Ule and Rickie Patani, a molecular neuroscientist and a clinical neurologist at University College London, and their colleagues, analyzed some 1,800 brain samples of ten brain regions from 480 deceased people aged 16 to 106, making for what they say is the most comprehensive analysis of human brain gene expression to date.

They found that glia — especially those in the hippocampus, a region associated with memory and spatial navigation, and the substantia nigra, related with reward and movement — change their gene expression over time. These regions are implicated in Alzheimer’s and Parkinson’s, so this research represents a new window into understanding those diseases.

The stakes are high, given that 46 million people worldwide live with dementia and 10 million with Parkinson’s. These numbers are bound to go up as the world grays: The U.N. estimates that between 2015 and 2030 the number of people aged 60 or older will grow from 901 million to 1.4 billion, a 56 percent increase.

Brain aging has a lot to do with what Ule calls the “identity crisis” that glia go through over time. You can see it in how patterns of gene expression change. “The expression pattern of genes is an indirect readout of cellular function,” Ule explained to Science of Us in an email. “This is telling us that these glial cells have somewhat distinct functions in each part of the brain, and we refer to this as their ‘regional identity.’ The ‘identity’ crisis is seen by the fact that glial expression patterns become more similar across the regions of brains from older individuals.” Like a charming downtown hollowed out by chain stores, the glia lose what makes them unique.

Other recent research has found that decades before Alzheimer’s presents as a clinical condition, it’s portended in the “cellular phase,” a preclinical time where cell types across the brain change their interactions. This study, then, is another step toward doctors being able to identify Alzheimer’s and Parkinson’s long before they manifest as full-blown diseases — thanks to considering a brain cell that had been largely overlooked. Samwise would be proud.

To Understand a Brain’s Age, Focus on More Than Neurons