Is Your Brain Older Than You Are?

The aging process affects individuals at highly variable rates, not only physically but also within the central nervous system. A powerful concept emerging in neuroscience to quantify this biological variability is the brain age gap. It is defined as the difference between an individual's predicted brain age and their actual chronological age. But why do our brains age differently? Which genes are responsible for this phenomenon? The Molecular Psychology Group (Sebastian Markett) did a genome-wide analysis in order to find genetic loci that are related to individual brain aging. Their results indicate that the brain age gap is heritable. The main locus included MAPT, which is known to encode a protein involved in Alzheimer's Disease. They also found relationships between genetics and other traits, such as mental health or lifestyle. If you want to know more about the brain age gap, read the nature aging article!

Abstract

Neuroimaging and machine learning are advancing research into the mechanisms of biological aging. In this field, ‘brain age gap’ has emerged as a promising magnetic resonance imaging-based biomarker that quantifies the deviation between an individual’s biological and chronological age of the brain. Here we conducted an in-depth genomic analysis of the brain age gap and its relationships with over 1,000 health traits. Genome-wide analyses in up to 56,348 individuals unveiled a heritability of 23–29% attributable to common genetic variants and highlighted 59 associated loci (39 novel). The leading locus encompasses MAPT, encoding the tau protein central to Alzheimer’s disease. Genetic correlations revealed relationships with mental health, physical health, lifestyle and socioeconomic traits, including depressed mood, diabetes, alcohol intake and income. Mendelian randomization indicated a causal role of high blood pressure and type 2 diabetes in accelerated brain aging. Our study highlights key genes and pathways related to neurogenesis, immune-system-related processes and small GTPase binding, laying the foundation for further mechanistic exploration.