| 描述信息 |
Although immunosenescence may result in increased morbidity and mortality, many mammals have evolved effective immune coping strategies to extend their lifespans. To identify the molecular clues of anti-immunosenescence, we first built the high-quality reference genome for a myotis bat, and then compared three long-lived mammals (i.e., naked mole rat, bat and human) versus the short-lived mammal, mouse, in splenic immune cells at single-cell resolution. A close relationship between B:T cell ratio and immunosenescence was detected, as B:T cell ratio is much higher in mouse than long-lived mammals and significantly increases during aging. Importantly, we identified several iron-related genes exhibiting anti-immunosenescence feature, especially the iron chaperon, Pcbp1, which was up-regulated in long-lived mammals but dramatically down-regulated during aging in all splenic immune cell types. Pcbp1 down-regulation during aging was also detected in hepatic but not pulmonary immune cells, which is consistent with the crucial roles of spleen and liver in organismal iron recycling. Furthermore, Pcbp1 perturbation in immune cell lines would result in cellular iron dyshomeostasis and senescence. Finally, we identified two transcription factors and one long non-coding RNA that could regulate Pcbp1. Together, our findings highlight the importance of iron homeostasis in splenic anti-immunosenescence, and provide unique insight for improving human healthspan. |
