Author: Berchtold NC1, Prieto GA2, Phelan M3, Gillen DL4, Baldi P5, Bennett DA6, Buchman AS6, Cotman CW7
Affiliation: <sup>1</sup>Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA. Electronic address: nberchto@uci.edu.
<sup>2</sup>Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA.
<sup>3</sup>Department of Statistics, University of California, Irvine, CA, USA.
<sup>4</sup>Statistics Department, University of California, Irvine, CA, USA.
<sup>5</sup>Institute for Genomics and Bioinformatics, School of Information and Computer Sciences, University of California, Irvine, CA, USA.
<sup>6</sup>Department of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
<sup>7</sup>Institute for Memory Impairments and Neurological Disorders, University of California-Irvine, Irvine, CA, USA; Department of Neurology, University of California-Irvine, Irvine, CA, USA.
Conference/Journal: Neurobiol Aging.
Date published: 2019 Feb 20
Other:
Volume ID: 78 , Pages: 142-154 , Special Notes: doi: 10.1016/j.neurobiolaging.2019.02.012. [Epub ahead of print] , Word Count: 298
Exercise has emerged as a powerful variable that can improve cognitive function and delay age-associated cognitive decline and Alzheimer's disease (AD); however, the underlying mechanisms are poorly understood. To determine if protective mechanisms may occur at the transcriptional level, we used microarrays to investigate the relationship between physical activity levels and gene expression patterns in the cognitively intact aged human hippocampus. In parallel, hippocampal gene expression patterns associated with aging and AD were assessed using publicly available microarray data profiling hippocampus from young (20-59 years), cognitively intact aging (73-95 years) and age-matched AD cases. To identify "anti-aging/AD" transcription patterns associated with physical activity, probesets significantly associated with both physical activity and aging/AD were identified and their directions of expression change in each condition were compared. Remarkably, of the 2210 probesets significant in both data sets, nearly 95% showed opposite transcription patterns with physical activity compared with aging/AD. The majority (>70%) of these anti-aging/AD genes showed increased expression with physical activity and decreased expression in aging/AD. Enrichment analysis of the anti-aging/AD genes showing increased expression in association with physical activity revealed strong overrepresentation of mitochondrial energy production and synaptic function, along with axonal function and myelin integrity. Synaptic genes were notably enriched for synaptic vesicle priming, release and recycling, glutamate and GABA signaling, and spine plasticity. Anti-aging/AD genes showing decreased expression in association with physical activity were enriched for transcription-related function (notably negative regulation of transcription). These data reveal that physical activity is associated with a more youthful profile in the hippocampus across multiple biological processes, providing a potential molecular foundation for how physical activity can delay age- and AD-related decline of hippocampal function.
Published by Elsevier Inc.
KEYWORDS: Axon; Exercise; Microarray; Mitochondria; Myelin; Plasticity; Synaptic vesicle trafficking; White matter
PMID: 30927700 DOI: 10.1016/j.neurobiolaging.2019.02.012