SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1beta

ABSTRACT: Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as brain ages is the aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we established a mechanistic link between chronic inflammation and aging microglia, and demonstrated a causal role of aging microglia in neurodegenerative cognitive deficits. Expression of microglial SIRT1 reduces with the aging of microglia. Genetic reduction of microglial SIRT1 elevates IL-1β selectively, and exacerbates cognitive deficits in aging and in transgenic mouse models of frontote

ORGANISM(S): Mus musculus

SUBMITTER: Giovanni Coppola 

PROVIDER: E-GEOD-56452 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress