Can consuming flavonoids restore old microglia to their youthful state?

Abstract

Microglial cells, which are resident macrophages in the central nervous system, are "primed" in the aged brain and are hypersensitive to messages emerging from immune-to-brain signaling pathways. Thus, in elderly individuals who have an infection, microglia overreact to signals from the peripheral immune system and produce excessive levels of cytokines, causing behavioral pathology including serious deficits in cognition. Importantly, recent studies indicate dietary flavonoids have anti-inflammatory properties and are capable of mitigating microglial cells in the brains of aged mice. Thus, dietary or supplemental flavonoids and other bioactive agents have the potential to restore the population of microglial cells in the elderly brain to its youthful state. This review briefly describes the immune-to-brain signaling pathways, consequences of microglial cell priming, and the potential of flavonoids to mitigate brain microglia and cognitive deficits induced by inflammatory cytokines.

Figure 1. Age-related priming of microglia produces an inflammatory gene expression profile in brain

(A) Microglia are normally quiescent but in old age they transition to a “primed” phenotype. Evidence suggests primed microglia cause low-grade inflammation. Further, primed microglia are hypersensitive to signals emerging from immune-to-brain signaling pathways, producing excessive levels of inflammatory cytokines and causing behavioral pathology including deficits in cognition (adapted from Dilger and Johnson, 2008). (B) Microarray analysis revealed a number of differentially expressed genes in brains of old mice compared to young adults. Nearly all of the inflammatory genes that were differentially expressed were up regulated in older mice (adapted from Godbout et al., 2005).

Figure 2. Flavonoids may impart an anti-inflammatory effect on brain microglia directly and indirectly

Flavonoids may regulate microglial cell activity directly by accessing the brain parenchyma and indirectly by dampening immune-to-brain signaling.