Telomeres and immunological diseases of aging.
A defining feature of the eukaryotic genome is the presence of linear chromosomes. This arrangement, however, poses several challenges with regard to chromosomal replication and maintenance. To prevent the loss of coding sequences and to suppress gross chromosomal rearrangements, linear chromosomes are capped by repetitive nucleoprotein structures, called telomeres. Each cell division results in a progressive shortening of telomeres that, below a certain threshold, promotes genome instability, senescence, and apoptosis. Telomeric erosion, maintenance, and repair take center stage in determining cell fate. Cells of the immune system are under enormous proliferative demand, stressing telomeric intactness. Lymphocytes are capable of upregulating telomerase, an enzyme that can elongate telomeric sequences and, thus, prolong cellular lifespan. Therefore, telomere dynamics are critical in preserving immune function and have become a focus for studies of immunosenescence and autoimmunity. In this review, we describe the role of telomeric nucleoproteins in shaping telomere architecture and in suppressing DNA damage responses. We summarize new insights into the regulation of telomerase activity, hereditary disorders associated with telomere dysfunction, the role of telomere loss in immune aging, and the impact of telomere dysfunction in chronic inflammatory disease.
Andrews
Nicolas P
NP
Lowance Center for Human Immunology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Fujii
Hiroshi
H
Goronzy
Jörg J
JJ
Weyand
Cornelia M
CM
D000375:Aging / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019588:Aging, Premature / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D000818:Animals; D016922:Cellular Senescence; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007154:Immune System Diseases / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D008954:Models, Biological; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*
D019098:Telomerase