Cognitive function typically declines with aging, but evidence suggests physical activity can help mitigate some of these declines. A recent study in mice found that exercise improves memory and spatial learning by inhibiting neuroinflammation, primarily via the actions of irisin, a myokine, and brain-derived neurotrophic factor (BDNF), a growth factor and signaling protein.

Researchers conducted a two-part study to investigate the effects of regular, low-intensity exercise on cognitive function in mouse models of inflammation-driven memory impairment and microglia (brain immune cell) degeneration.

First, they assessed the animals' neuroprotective and antioxidant marker levels and subjected them to various memory and behavioral tests. They found that exercise reduced memory problems and cognitive losses by increasing the expression of irisin. In turn, irisin activated BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2), reducing inflammation and blocking the activity of BACE-1, an enzyme critical for amyloid-beta production.

Then, they studied the effects of irisin on microglia. They found irisin blocked the NF-κB/MAPK/IRF3 pro-inflammatory signaling pathway. It also lowered pro-inflammatory markers while increasing the expression of Nrf2.

Nrf2 is a cellular protein that activates the transcription of more than 200 cytoprotective proteins that protect against oxidative stress due to injury, inflammation, and normal aging processes. It is an element of the Keap1-Nrf2-ARE biological pathway, a mediator of protective responses to oxidative and electrophilic stressors. Hormetic stressors like exercise, heat exposure, and dietary components trigger Nrf2 activity. Sulforaphane, a compound derived from broccoli, is the most potent naturally occurring hormetic inducer of Nrf2 activity. Learn more about Nrf2 in this clip featuring Dr. Jed Fahey.

• For more information about the cognitive benefits of exercise (as well as other lifestyle behaviors), check out our Cognitive Enhancement Blueprint in the Member Library.