Open AccessEpigenomic drivers of immune dysfunction in aging
Author(s) -
Keenan Christine R.,
Allan Rhys S.
Publication year - 2019
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12878
Subject(s) - biology , immune system , immunosenescence , epigenetics , telomere , genome instability , immunology , epigenomics , premature aging , chromatin , immunity , immunocompetence , innate immune system , phenotype , inflammation , dna damage , genetics , dna methylation , dna , gene expression , gene
Aging inevitably leads to reduced immune function, leaving the elderly more susceptible to infections, less able to respond to pathogen challenges, and less responsive to preventative vaccinations. No cell type is exempt from the ravages of age, and extensive studies have found age‐related alterations in the frequencies and functions of both stem and progenitor cells, as well as effector cells of both the innate and adaptive immune systems. The intrinsic functional reduction in immune competence is also associated with low‐grade chronic inflammation, termed “inflamm‐aging,” which further perpetuates immune dysfunction. While many of these age‐related cellular changes are well characterized, understanding the molecular changes that underpin the functional decline has proven more difficult. Changes in chromatin are increasingly appreciated as a causative mechanism of cellular and organismal aging across species. These changes include increased genomic instability through loss of heterochromatin and increased DNA damage, telomere attrition, and epigenetic alterations. In this review, we discuss the connections between chromatin, immunocompetence, and the loss of function associated with mammalian immune aging. Through understanding the molecular events which underpin the phenotypic changes observed in the aged immune system, it is hoped that the aged immune system can be restored to provide youthful immunity once more.