ABSTRACT

Objective: Apart from the counter-regulation of angiotensin II levels in the renin-angiotensin system, angiotensin-converting enzyme 2 (ACE2) acts as a receptor for SARS-CoV-2, which is activated by transmembrane serine protease 2 (TMPRSS2) in target cells. Sirtuin 1 (SIRT1), an aging-related protein, controls ACE2 transcription in energy stress situations. This study aimed to evaluate the protein expression of ACE2, TMPRSS2, and SIRT1 in the lungs of children, adults, and elderly individuals. Methods: We used immunohistochemistry and software-assisted analysis to evaluate ACE2, TMPRSS2, and SIRT1 protein expression in autopsied lung tissue with minimal histological abnormalities and no clinical diagnosis of pulmonary disease or infection. The study population included 25 children (newborn to 19-year-old), 7 adults (20- to 59-year-old), and 11 elderly individuals (60- to 95-year-old). Of those 43 patients, 19 were female and 24 were male. Results: ACE2, TMPRSS2, and SIRT1 proteins were more expressed in the pulmonary parenchyma of children than in that of adults (p = 0.043, p = 0.008, and p = 0.032, respectively). SIRT1 expression was higher in the alveoli of children than in those of elderly patients (p = 0.008). No sex-based differences were observed. Spearman's correlation coefficient showed that ACE2, TMPRSS2, and SIRT1 expression decreased with aging. Conclusions: ACE2, TMPRSS2, and SIRT1 were more expressed in the lung parenchyma (but not in the airways) of children than in that of older individuals. This could contribute to less severe COVID-19 lung disease in children.

Keywords: Angiotensin-converting enzyme 2; TMPRSS2 protein, human; Sirtuin 1; Lung; Aging.

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