Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

Abstract

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.

Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches

“…Generally, pulmonary fibrosis development is often preceded by acute lung inflammation, caused by viral and bacterial infections, ionizing radiation, chemotherapy, air irritants and pollutants [ 15 , 16 , 17 , 18 ], which were not resolved in time and resulted in the deposition of fibrotic tissue in the lungs and respiratory dysfunction [ 3 ]. It should be noted that the etiology of IPF is unknown and causal agent or specific association has not been determined [ 19 ], but among the many intrinsic and extrinsic risk factors, viral infections [ 20 ], gastro-esophageal reflux disease (GERD)-related micro-aspiration [ 21 ], genetic predisposition [ 22 , 23 ] are distinguished. One of the noteworthy risk factors of IPF development is GERD.…”

SARS-CoV-2 mediated dysregulation in cell signaling events drives the severity of COVID-19

“…A telomere is a region of noncoding DNA comprising tandem repeats of TTAGGG at the end of linear chromosomes attached with specialized protein and provide genetic stability and proper cell functioning ( Ruiz et al, 2022 ). During the normal process of DNA replication in somatic cell division, the length of telomere tends to decrease gradually that causes a progressive telomere shortening (TS) with advancing of age ( Ruiz et al, 2022 ).…”

“…A telomere is a region of noncoding DNA comprising tandem repeats of TTAGGG at the end of linear chromosomes attached with specialized protein and provide genetic stability and proper cell functioning ( Ruiz et al, 2022 ). During the normal process of DNA replication in somatic cell division, the length of telomere tends to decrease gradually that causes a progressive telomere shortening (TS) with advancing of age ( Ruiz et al, 2022 ). The progressive shortening of telomere reaches a dysfunctional state in aged individuals with impaired host response to cellular stress, inflammatory responses and mitochondrial defective function ( Lara et al, 2020 ).…”

The effect of high polycyclic aromatic hydrocarbon exposure on biological aging indicators

“…Their length measured in blood lymphocytes is considered an indicator of biological aging [50]. Loss of telomere sequence in lymphocytes has been also related to adverse age-related outcomes, in particular CVD [51,52] and respiratory diseases [53]. Exposure to PAHs may pose a risk not only for lung cancer, but also for CVD, including atherosclerosis, hypertension, thrombosis and myocardial infarction [54].…”