A standardized randomized 6-month aerobic exercise-training down-regulated pro-inflammatory genes, but up-regulated anti-inflammatory, neuron survival and axon growth-related genes.

There is considerable support for the view that aerobic exercise may confer cognitive benefits to mild cognitively impaired elderly persons. However, the biological mechanisms mediating these effects are not entirely clear. As a preliminary step towards informing this gap in knowledge, we enrolled older adults confirmed to have mild cognitive impairment (MCI) in a 6-month exercise program. Male and female subjects were randomized into a 6-month program of either aerobic or stretch (control) exercise. Data collected from the first 10 completers, aerobic exercise (n=5) or stretch (control) exercise (n=5), were used to determine intervention-induced changes in the global gene expression profiles of the aerobic and stretch groups. Using microarray, we identified genes with altered expression (relative to baseline values) in response to the 6-month exercise intervention. Genes whose expression were altered by at least two-fold, and met the p-value cutoff of 0.01 were inputted into the Ingenuity Pathway Knowledge Base Library to generate gene-interaction networks. After a 6-month aerobic exercise-training, genes promoting inflammation became down-regulated, whereas genes having anti-inflammatory properties and those modulating immune function or promoting neuron survival and axon growth, became up-regulated (all fold change≥±2.0, p<0.01). These changes were not observed in the stretch group. Importantly, the differences in the expression profiles correlated with significant improvement in maximal oxygen uptake (VO2max) in the aerobic program as opposed to the stretch group. We conclude that three distinct cellular pathways may collectively influence the training effects of aerobic exercise in MCI subjects. We plan to confirm these effects using rt-PCR and correlate such changes with the cognitive phenotype.