Epigenomic drivers of immune dysfunction in aging
Author(s)
Keenan, CR; Allan, RS;
Journal Title
Aging Cell
Publication Type
Journal Article in press
Abstract
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.
Publisher
Wiley
Research Division(s)
Molecular Immunology
PubMed ID
30488545
Open Access at Publisher's Site
https://doi.org/10.1111/acel.12878
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2018-12-18 02:54:29
Last Modified: 2018-12-18 03:39:04
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