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Single-cell transcriptomic atlas of primate cardiopulmonary aging
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Journal Article
Single-cell transcriptomic atlas of primate cardiopulmonary aging
2021
Overview
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.
Publisher
Springer Singapore,Nature Publishing Group
Subject
/ ACE2
/ Aging
/ Alveolar Epithelial Cells - cytology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - virology
/ Alveoli
/ Angiotensin-converting enzyme 2
/ Angiotensin-Converting Enzyme 2 - genetics
/ Angiotensin-Converting Enzyme 2 - metabolism
/ Animals
/ Ascorbic Acid - pharmacology
/ Biomedical and Life Sciences
/ COVID-19
/ Endothelial Cells - cytology
/ Endothelial Cells - metabolism
/ Endothelial Cells - virology
/ Humans
/ Interleukin-7 - pharmacology
/ Myocytes, Cardiac - cytology
/ Myocytes, Cardiac - metabolism
/ Myocytes, Cardiac - virology
/ Primates
/ RNA-Seq
/ SARS-CoV-2 - isolation & purification
/ Severe acute respiratory syndrome coronavirus 2
