%0 Journal Article
%T Functional pathways regulated by microRNA networks in CD8 T©\cell aging
%A Claire E. Gustafson
%A Cornelia M. Weyand
%A Jun Jin
%A Mary M. Cavanagh
%J Archive of "Aging Cell".
%D 2019
%R 10.1111/acel.12879
%X One of the most prominent immunological changes during human aging is the alteration in CD8 T©\cell subset distribution, predominated by a loss of na£¿ve CD8 T cells. The molecular mechanisms that contribute to the loss of na£¿ve CD8 T©\cells during aging remain unclear. Considering that many CD8 T©\cell functions are influenced by microRNAs (miRNAs), we explored miRNA expression profiling to identify novel dysfunctions that contribute to na£¿ve CD8 T©\cell loss during aging. Here, we describe age©\dependent miRNA expression changes in na£¿ve, central memory, and effector memory CD8 T©\cell subsets. Changes in old na£¿ve CD8 T©\cells partially resembled those driven by an underlying shift in cellular differentiation toward a young central memory phenotype. Pathways enriched for targets of age©\dependent miRNAs included FOXO1, NF©\¦ÊB, and PI3K©\AKT signaling. Transcriptome analysis of old na£¿ve CD8 T©\cells yielded corresponding patterns that correlated to those seen with reduced FOXO1 or altered NF©\¦ÊB activities. Of particular interest, IL©\7R expression, controlled by FOXO1 signaling, declines on na£¿ve CD8 T cells with age and directly correlates with the frequencies of na£¿ve CD8 T cells. Thus, age©\associated changes in miRNA networks may ultimately contribute to the failure in CD8 T©\cell homeostasis exemplified by the loss in na£¿ve cells
%K cellular homeostasis
%K FOXO1
%K IL©\7 receptor
%K immunosenescence
%K posttranscriptional regulation
%K TNF©\alpha
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351841/