The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect?

Abstract

Telomeres are specialized nucleoprotein structures located at the end of linear chromosomes and telomerase is the enzyme responsible for telomere elongation. Telomerase activity is a key component of many cancer cells responsible for rapid cell division but it has also been found by many laboratories around the world that telomere/telomerase biology is dysfunctional in many other chronic conditions as well. These conditions are characterized by chronic inflammation, a situation mostly overlooked by physicians regarding patient treatment. Among others, these conditions include diabetes, renal failure, chronic obstructive pulmonary disease, etc. Since researchers have in many cases identified the association between telomerase and inflammation but there are still many missing links regarding this correlation, the latest findings about this phenomenon will be discussed by reviewing the literature. Our focus will be describing telomere/telomerase status in chronic diseases under the prism of inflammation, reporting molecular findings where available and proposing possible future approaches.

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases

“…Chondrocytes and peripheral blood leukocytes in elderly individuals with osteoporosis have shorter telomeres, and restoring telomerase activity in osteoblasts increases bone deposition 70 . Mutations that result in TERT loss of function and telomere attrition also cause ageing-associated lung emphysema and fibrosis 71 . Studies in mouse models suggest that telomere attrition accelerates the development of ageing-related lung emphysema by reducing the ability of the lungs to withstand toxin-induced stress 72,73 .…”

“…Studies in mouse models suggest that telomere attrition accelerates the development of ageing-related lung emphysema by reducing the ability of the lungs to withstand toxin-induced stress 72,73 . In CKD, telomere attrition was found to reduce cell viability and increase renal injury upon ischaemia–reperfusion 71 . The same relationship may hold for pancreatic β-cells, the survival and functionality of which are compromised under high blood sugar levels in Tert -knockout mice 71 .…”

“…In CKD, telomere attrition was found to reduce cell viability and increase renal injury upon ischaemia–reperfusion 71 . The same relationship may hold for pancreatic β-cells, the survival and functionality of which are compromised under high blood sugar levels in Tert -knockout mice 71 .…”

Characterizing the “POAGome”: A bioinformatics-driven approach to primary open-angle glaucoma

“…Interestingly, the top associated diseases to this gene set were POAG and osteoarthritis, and the two top upstream regulators for this gene input list were TERT (telomerase reverse transcriptase) and TGFB1 (Supplementary Table 9). Dysregulation of TERT (telomerase reverse transcriptase) has been shown to be involved in the pathogenesis of chronic inflammatory states, and also has an important role in regulating apoptosis and cellular senescence (Cao et al, 2002; Kordinas et al, 2016). Limited research has been performed to determine the specific role of TERT in neurodegenerative diseases, however, there is some evidence that the absence of TERT in microglia and hippocampal neurons may increase the risk of the development of tauopathies, like Alzheimer’s disease (Spilsbury et al, 2015).…”

Telegraphing your telomere length to the next generation

“…Our preoccupation with aging today exceeds the boundaries scientific curiosity back when the Bnatural order of things^was viewed as a means for population control in societies facing food shortages, disease, and lifespans inconsistent with prospects for controlling the inevitable. Rather, the telomere stands firm as a sentinel of longevity capping the ends of our chromosomes, as failure to do so sets into action many of those diseases that compromise both the quality and quantity of life that can be expected [1]. And to no surprise, telomere lengthening or shortening has figured prominently in the fields of reproductive biology and medicine in an atmosphere of flexible life cycles oscillating between, and in sequence from generation to generation with, the nascent interchangeability of gametes and stem cells and the hopes for immortalization resulting from somatic cell nuclear transfer technology [2].…”