Shorter telomeres in children with severe asthma, an indicative of accelerated aging.

Frederico Friedrich,Marcus H Jones,Mariana M Parisi,Florencia M Barbé-Tuana,Fátima T.C.R Guma,Paulo M.C Pitrez,Vinícius Pierdoná,Leonardo A Pinto,Lucas K Grun,Renato T Stein

doi:10.18632/aging.202527

Abstract

Severe therapy-resistant asthma (STRA) is closely associated with distinct clinical and inflammatory pheno-endotypes, which may contribute to the development of age-related comorbidities. Evidence has demonstrated a contribution of accelerated telomere shortening on the poor prognosis of respiratory diseases in adults. Eotaxin-1 (CCL11) is an important chemokine for eosinophilic recruitment and the progression of asthma. In the last years has also been proposed as an age-promoting factor. This study aimed to investigate the association of relative telomere length (rTL) and eotaxin-1 in asthmatic children. Children aged 8-14 years (n=267) were classified as healthy control (HC, n=126), mild asthma (MA, n=124) or severe therapy-resistant asthma (STRA, n=17). rTL was performed by qPCR from peripheral blood. Eotaxin-1 was quantified by ELISA from fresh-frozen plasma. STRA had shorter telomeres compared to HC (p=0.02) and MA (p=0.006). Eotaxin-1 levels were up-regulated in STRA [median; IQR25-75)] [(1,190 pg/mL; 108–2,510)] compared to MA [(638 pg/mL; 134–1,460)] (p=0.03) or HC [(627 pg/mL; 108–1,750)] (p<0.01). Additionally, shorter telomeres were inversely correlated with eotaxin-1 levels in STRA (r=-0.6, p=0.013). Our results suggest that short telomeres and up-regulated eotaxin-1, features of accelerated aging, could prematurely contribute to a senescent phenotype increasing the risk for early development of age-related diseases in asthma.

Highlights

Asthma is a complex, heterogeneous, and prevalent chronic respiratory disease that can develop early during childhood and persist through life
The severe therapy-resistant asthma (STRA) group had lower height than healthy controls (HC) and mild asthmatics (MA), but no difference was observed in age (p=0.080), weight (p=0.108), proportion of ethnicity (p=0.176) or sex (p=0.359) between groups
We demonstrate that the upregulation of the chemokine eotaxin-1 inversely correlates with telomere length (TL) in the STRA group but not MA or HC

Summary

Introduction

Heterogeneous, and prevalent chronic respiratory disease that can develop early during childhood and persist through life. It is characterized by variable airflow obstruction and tissue remodeling of the airways. Individuals with persistent or severe asthma, where continuous activation of the immune cells and eosinophilic activity is not satisfactorily controlled have shorter telomeres than healthy individuals [3]. Taken together, these studies suggest that telomere length (TL) analysis could work as a predictor of disease progression in respiratory diseases. We investigated differences in TL and eotaxin-1 in children with STRA and compared it to mild asthmatics (MA), and healthy controls (HC)

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