Telomere length dynamics over 10-years and related outcomes in patients with COPD

Córdoba-Lanús, Elizabeth; Cazorla-Rivero, Sara; García‐Bello, Miguel Ángel; Mayato, Delia; Gonzalvo, F; Ayra-Plasencia, Jessel; Celli, Bartolomé R.; Casanova, Ciro

doi:10.1186/s12931-021-01616-z

Cited by 15 publications

(13 citation statements)

References 47 publications

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“…This may be particularly relevant in the young individuals since we observed here, for the first time to our knowledge, that telomere shortening also occur in the young patients with COPD with severe airflow limitation, a population that may be more susceptible to the environmental exposures associated to COPD and/or carry a genetic background predisposing them to telomere attrition. This finding agrees with the relationship between the accelerated telomere shortening and progressive worsening of pulmonary gas exchange previously described ( 40 ).…”

Section: Discussionsupporting

confidence: 93%

“…( 13 ), albeit the latter was not reproduced in other investigations ( 13 – 15 , 38 , 39 ). Recently, a longitudinal study in patients with COPD ( 40 ) showed an association between the accelerated telomere shortening, progressive worsening of the pulmonary gas exchange, and all-cause mortality risk. Moreover, some studies have included young and old individuals (14, 32) but none of them have stratified the analysis by age group, nor by the presence of COPD according to age.…”

Section: Discussionmentioning

confidence: 99%

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Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD

et al. 2021

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Accelerated ageing is implicated in the pathogenesis of respiratory diseases as chronic obstructive pulmonary disease (COPD), but recent evidence indicates that the COPD can have roots early in life. Here we hypothesise that the accelerated ageing markers might have a role in the pathobiology of young COPD. The objective of this study was to compare two hallmarks of ageing, telomere length (TL), and mitochondrial DNA copy number (mtDNA-CN, as a surrogate marker of mitochondrial dysfunction) in young (≤ 50 years) and old (>50 years) smokers, with and without COPD. Both, TL and mtDNA-CN were measured in whole blood DNA by quantitative PCR [qPCR] in: (1) young ever smokers with (n = 81) or without (n = 166) COPD; and (2) old ever smokers with (n = 159) or without (n = 29) COPD. A multivariable linear regression was used to assess the association of TL and mtDNA-CN with lung function. We observed that in the entire study population, TL and mtDNA-CN decreased with age, and the former but not the latter related to FEV1/FVC (%), FEV1 (% ref.), and DLCO (% ref.). The short telomeres were found both in the young and old patients with severe COPD (FEV1 <50% ref.). In addition, we found that TL and mtDNA-CN were significantly correlated, but their relationship was positive in younger while negative in the older patients with COPD, suggesting a mitochondrial dysfunction. We conclude that TL, but not mtDNA-CN, is associated with the lung function impairment. Both young and old patients with severe COPD have evidence of accelerated ageing (shorter TL) but differ in the direction of the correlation between TL and mtDNA-CN in relation to age.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD

et al. 2021

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“…Furthermore, COPD has often been proposed to be a disease caused by accelerated immune aging (133,134). A recently published study conducted by Coŕdoba-Lanuś et al monitored telomere length of patients with COPD over a 10 year period and found an association between accelerated telomere shortening and progressive decline in lung function, such as worsening of gas exchange and lung hyperinflation in COPD patients (135).…”

Section: Hiv and Copdmentioning

confidence: 99%

Pulmonary Immune Dysregulation and Viral Persistence During HIV Infection

2022

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Despite the success of antiretroviral therapy (ART), people living with HIV continue to suffer from high burdens of respiratory infections, lung cancers and chronic lung disease at a higher rate than the general population. The lung mucosa, a previously neglected HIV reservoir site, is of particular importance in this phenomenon. Because ART does not eliminate the virus, residual levels of HIV that remain in deep tissues lead to chronic immune activation and pulmonary inflammatory pathologies. In turn, continuous pulmonary and systemic inflammation cause immune cell exhaustion and pulmonary immune dysregulation, creating a pro-inflammatory environment ideal for HIV reservoir persistence. Moreover, smoking, gut and lung dysbiosis and co-infections further fuel the vicious cycle of residual viral replication which, in turn, contributes to inflammation and immune cell proliferation, further maintaining the HIV reservoir. Herein, we discuss the recent evidence supporting the notion that the lungs serve as an HIV viral reservoir. We will explore how smoking, changes in the microbiome, and common co-infections seen in PLWH contribute to HIV persistence, pulmonary immune dysregulation, and high rates of infectious and non-infectious lung disease among these individuals.

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“…Patients with COPD present shorter leucocyte telomeres than smokers without COPD and healthy subjects [60,61]. Further, compared to smoking controls, patients with COPD exhibit an accelerated telomere shortening that is associated with worse alveolar gas exchange, worse lung hyperinflation, and the presence of extrapulmonary affections [62]. Moreover, in patients with COPD, shorter telomeres are associated with an increased risk of cancer and all-cause mortality [62,63].…”

Section: Aging-related Pathways In Copd and Ipfmentioning

confidence: 99%

“…Further, compared to smoking controls, patients with COPD exhibit an accelerated telomere shortening that is associated with worse alveolar gas exchange, worse lung hyperinflation, and the presence of extrapulmonary affections [62]. Moreover, in patients with COPD, shorter telomeres are associated with an increased risk of cancer and all-cause mortality [62,63]. However, when mendelian randomization was used to investigate causality between TL and incidence of COPD in a large cohort of 11,413 patients with COPD and more than 400,000 controls, there was no evidence that telomere shortening may cause COPD [56].…”

Section: Aging-related Pathways In Copd and Ipfmentioning

confidence: 99%

COPD, Pulmonary Fibrosis and ILAs in Aging Smokers: The Paradox of Striking Different Responses to the Major Risk Factors

Beghè

Cerri

Fabbri

et al. 2021

IJMS

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Aging and smoking are associated with the progressive development of three main pulmonary diseases: chronic obstructive pulmonary disease (COPD), interstitial lung abnormalities (ILAs), and idiopathic pulmonary fibrosis (IPF). All three manifest mainly after the age of 60 years, but with different natural histories and prevalence: COPD prevalence increases with age to >40%, ILA prevalence is 8%, and IPF, a rare disease, is 0.0005–0.002%. While COPD and ILAs may be associated with gradual progression and mortality, the natural history of IPF remains obscure, with a worse prognosis and life expectancy of 2–5 years from diagnosis. Acute exacerbations are significant events in both COPD and IPF, with a much worse prognosis in IPF. This perspective discusses the paradox of the striking pathological and pathophysiologic responses on the background of the same main risk factors, aging and smoking, suggesting two distinct pathophysiologic processes for COPD and ILAs on one side and IPF on the other side. Pathologically, COPD is characterized by small airways fibrosis and remodeling, with the destruction of the lung parenchyma. By contrast, IPF almost exclusively affects the lung parenchyma and interstitium. ILAs are a heterogenous group of diseases, a minority of which present with the alveolar and interstitial abnormalities of interstitial lung disease.

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Telomere length dynamics over 10-years and related outcomes in patients with COPD

Cited by 15 publications

References 47 publications

Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD

Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD

Pulmonary Immune Dysregulation and Viral Persistence During HIV Infection

COPD, Pulmonary Fibrosis and ILAs in Aging Smokers: The Paradox of Striking Different Responses to the Major Risk Factors

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