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Nov 5, 2013

Genes Shared by Relatives Shown to Influence Brain Aging

  • Early results from a long-term research project indicate that certain age-related declines in brain function are influenced by genes. This project, the Genetics of Brain Structure and Function Study, aims to identify the genes that predispose people to brain disorders and mental illnesses. By establishing that genetic links do exist, the project has made a crucial first step toward its ultimate goal.

    For this stage of the project, researchers were focused on Mexican American families in San Antonio. In all, 1,129 people from 30 large, extended families were enrolled to form a large cohort of randomly selected pedigrees. In this cohort, researchers documented profound aging effects from young adulthood to old age (18–83 years) on neurocognitive ability and diffusion-based white-matter measures.

    The researchers detailed their results November 4 in the Proceedings of the National Academy of Sciences, in a paper entitled “Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging.” They described evaluating neurocognitive ability via tests of processing speed, working memory, declarative memory, and intelligence. White-matter measures depended on brain imaging studies.

    The researchers, based at the Texas Biomedical Research Institute and Yale University, wrote that despite significant phenotypic correlation between neurocognitive ability and white-matter integrity, no evidence for shared genetic determination was observed: “Applying a gene-by-environment interaction analysis where age is an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration with age. In contrast, increasing white-matter incoherence with age appears to be nongenetic.”

    The researchers also examined gene-by-aging (G × A) interactions. These analyses, which directly tested changes in genetic influence with aging, identified that the heritability of processing speed, attention, and memory measures changed with advancing age.

    According to the researchers, these results imply that fluctuations in genetic influence with advancing age trigger at least a portion of the neurocognitive decline seen in normal aging: “Our analyses suggest that for some traits, G × A interactions are due to changes in the action of specific genes, whereas for other measures, G × A interactions are associated with differences in the exact genes that influence the trait.”

    First author of the paper and associate professor of psychology at Yale, David Glahn, Ph.D., said, “A key advantage of this study is that we specifically focused on large extended families, and so we were able to disentangle genetic from nongenetic influences on the aging process.”

    Expressing confidence in the utility of their approach, the authors concluded that their results “demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging.”



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