Group of Inflammation and Cellular Senescence, Laboratory of Immunobiology, School of Health, Sciences and Life, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Postgraduate Program in Cellular and Molecular Biology, School of Health, Sciences and Life, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Aging (Albany NY). 2021 Jan 20;13(2):1686-1691. doi: 10.18632/aging.202527.
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 (=0.02) and MA (=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)] (=0.03) or HC [(627 pg/mL; 108-1,750)] (<0.01). Additionally, shorter telomeres were inversely correlated with eotaxin-1 levels in STRA (r=-0.6, =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.
严重治疗抵抗性哮喘（STRA）与明显的临床和炎症表型密切相关，这可能导致与年龄相关的合并症的发生。有证据表明，端粒缩短加速与成人呼吸疾病的不良预后有关。嗜酸性粒细胞趋化因子-1（CCL11）是嗜酸性粒细胞募集和哮喘进展的重要趋化因子。近年来，它也被提出是一种促进衰老的因素。本研究旨在探讨哮喘儿童相对端粒长度（rTL）与嗜酸性粒细胞趋化因子-1的相关性。将 8-14 岁的儿童（n=267）分为健康对照组（HC，n=126）、轻度哮喘组（MA，n=124）或严重治疗抵抗性哮喘组（STRA，n=17）。采用 qPCR 法从外周血中检测 rTL。采用 ELISA 法从新鲜冷冻血浆中检测嗜酸性粒细胞趋化因子-1。与 HC（=0.02）和 MA（=0.006）相比，STRA 的端粒较短（=0.02）。与 MA（中位数；1/4-3/4 分位）[(638 pg/ml；134-1460)]相比，STRA 中嗜酸性粒细胞趋化因子-1 水平升高[中位数；1/4-3/4 分位]（1190 pg/ml；108-2510）（=0.03）或 HC（中位数；1/4-3/4 分位）[627 pg/ml；108-1750]（<0.01）。此外，STRA 中较短的端粒与嗜酸性粒细胞趋化因子-1水平呈负相关（r=-0.6，=0.013）。我们的结果表明，加速衰老的特征，即短端粒和上调的嗜酸性粒细胞趋化因子-1，可能会过早地导致衰老表型增加，从而增加哮喘患者发生与年龄相关疾病的早期风险。
