In aging mice, myeloid cell bioenergetics are suppressed in response to increased signaling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In aging macrophages and microglia, PGE2 signaling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. Inhibition of myeloid EP2 signaling restores youthful energy metabolism in peripheral macrophages and microglia, rejuvenates systemic and brain inflammatory states, and prevents loss of hippocampal synaptic plasticity and spatial memory. Blockade of peripheral myeloid EP2 signaling is sufficient to restore cognition in aged mice.
METHOD OF TREATMENT TO PREVENT OR REVERSE AGE-ASSOCIATED INFLAMMATION, COGNITIVE DECLINE, AND NEURODEGENERATION