In this study, we provide a comprehensive atlas of human circulating immune cell aging. Furthermore, we reveal novel aging-related genes and adaptive immune dysregulation, thus defining the potential contributions of aging-related immune cell disorganization to the high severity rate of aged COVID-19 patients (Fig. 8). We believe that these findings will serve as a foundation from which to explore unknown facets of aging etiology and a reference for the broad scientific community interested in immunology and aging.
Figure 8 Aging reprograms human immune cell landscape, and increases the susceptibility and vulnerability of COVID-19. Schematic illustrating the key innate and adaptive immune functional alterations identified in PBMCs influenced by aging and COVID-19. Young healthy individuals maintain homeostasis in immune system which could timely eliminate pathogen. Aging leads to the increase of monocytes (MCs) and the decrease of T cells (TCs) in the immune system. Aging promotes the polarization of TCs from naive and memory to effector, exhausted and regulatory subtypes and increases the numbers of late natural killer (NK) cells, age-associated B cells, inflammatory MCs, and dysfunctional dendritic cells (DCs). Moreover, aging induces increased expression of genes related to SARS-CoV-2 susceptibility, suggesting increased susceptibility in the elderly. Importantly, aging induces DCs to lose the antigen-presenting ability, and turn to an inflammatory state. Together, a dysregulated immune system and increased expression of genes associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly