Single-cell transcriptomic atlas of primate cardiopulmonary aging

Ma, Shuai; Sun, Shuhui; Li, Jiaming; Fan, Yanling; Qu, Jing; Sun, Liang; Wang, Si; Zhang, Yiyuan; Yang, Shanshan; Liu, Zunpeng; Wu, Zeming; Zhang, Sheng; Wang, Qiaoran; Zheng, Aihua; Duo, Shuguang; Yu, Yang; Belmonte, Juan Carlos Izpisua; Chan, Piu; Zhou, Qi; Song, Moshi; Zhang, Weiqi; Liu, Guang-Hui

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.