Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 14 No. 4 • September 2011

Immune Gene Upregulation in Aging Mouse Brain Parallels
Declines in Cognition, Motivation, and Locomotion

In a new paper1 researchers studied declines in cognitive performance resulting from age-related changes in the prefrontal cortex (PFC) of mice. As they note, this brain region is particularly sensitive to age-related decline, as reflected in deficits in cognition, motivation, and locomotor behavior. The mouse PFC is functionally and anatomically homologous to the PFC in higher mammals.1

The researchers1 explain: “There is substantial evidence that aging is associated with increases in peripheral gene upregulation and that this is, in turn, associated with cognitive dysfunction.” Thus, they examined the levels of pro-inflammatory cytokines in the serum of mice. “Aging was associated with upregulation of numerous CD antigens, chemokine related genes, complement genes, genes in the JAK-STAT and/or interferon signaling pathway, cellular adhesion genes, MHC related genes, and Toll-like receptors in the CD11b+ cells.” Toll-like receptor2 was shown in Table 3 to be one of the upregulated genes.

“Immune gene upregulation, especially within the CNS [central nervous system], has been demonstrated to impair a variety of cognitive domains, including learning, memory, and attention. While this study is the first, to our knowledge, to relate behavior with whole genome expression changes within the PFC of rodents, others have investigated PFC related behavior under inflammatory conditions. For example, rats given chronic ventricular administration of lipopolysaccharide (LPS), a potent activator of innate immunity, are significantly impaired in PFC dependent spatial working memory tasks. Similarly, there is evidence that age-related neuroimmune gene upregulation in humans is associated with cognitive decline.”1


  1. Bordner et al. Parallel declines in cognition, motivation, and locomotion in aging mice: Exp Gerontol 46:643-59 (2011).

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