Journal
CELL RESEARCH
Volume 31, Issue 4, Pages 415-432Publisher
SPRINGERNATURE
DOI: 10.1038/s41422-020-00412-6
Keywords
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Categories
Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010100]
- National Key RAMP
- D Program of China [2018YFC2000100, 2017YFA0102802, 2017YFA0103304, 2018YFA0107203]
- National Natural Science Foundation of China [81625009, 91749202, 81861168034, 81921006, 31671429, 91949209, 91749123, 81671377, 81822018, 81870228, 81922027, 31900523, 81701388, 81901432, 91849132]
- Program of the Beijing Municipal Science and Technology Commission [Z191100001519005]
- Beijing Natural Science Foundation [Z190019]
- Beijing Municipal Commission of Health and Family Planning [PXM2018_026283_000002]
- Advanced Innovation Center for Human Brain Protection [3500-1192012]
- Key Research Program of the Chinese Academy of Sciences [KFZD-SW-221]
- K.C. Wong Education Foundation [GJTD-2019-06, GJTD-2019-08]
- Youth Innovation Promotion Association of CAS [2016093]
- State Key Laboratory of Stem Cell and Reproductive Biology
- State Key Laboratory of Membrane Biology
- CAMS Innovation Fund for Medical Sciences [2018-I2M-1-002]
- Beijing Hospital Nova Project [BJ-2018-139]
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The research indicates that aging is associated with increased systemic inflammation and compromised virus defense in the cardiopulmonary system. With age, expression of the SARS-CoV-2 receptor ACE2 increases, while the accumulation of the cytokine IL7 induces ACE2 expression. Treatment with vitamin C can block IL7-induced ACE2 expression, suggesting that geroprotective strategies may reduce the severity of COVID-19 in the elderly.
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-kappa B-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.
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