Decoding aging-dependent regenerative decline across tissues at single-cell resolution

• DOI: 10.1016/j.stem.2023.09.014
• Publication Date: 2023-10-27T14:27:11Z
• Authors: Yusheng Cai; Muzhao Xiong; Zijuan Xin; Chengyu Liu; Jie Ren; Xiying Yang; Jinghui Lei; Wei Li; Feifei Liu; Qun Chu; Yiyuan Zhang; Jian Yin; Yanxia Ye; Dingyi Liu; Yanling Fan; Shuhui Sun; Yaobin Jing; Qian Zhao; Liyun Zhao; Shanshan Che; Yandong Zheng; Haoteng Yan; Shuai Ma; Si Wang; Juan Carlos Izpis...; Jing Qu; Weiqi Zhang; Guang-Hui Liu
• Keywords: Senescence

Regeneration across tissues and organs exhibits significant variation throughout the body and undergoes a progressive decline with age. To decode the relationships between aging and regenerative capacity, we conducted a comprehensive single-cell transcriptome analysis of regeneration in eight tissues from young and aged mice. We employed diverse analytical models to study tissue regeneration and unveiled the intricate cellular and molecular mechanisms underlying the attenuated regenerative processes observed in aged tissues. Specifically, we identified compromised stem cell mobility and inadequate angiogenesis as prominent contributors to this age-associated decline in regenerative capacity. Moreover, we discovered a unique subset of Arg1+ macrophages that were activated in young tissues but suppressed in aged regenerating tissues, suggesting their important role in age-related immune response disparities during regeneration. This study provides a comprehensive single-cell resource for identifying potential targets for interventions aimed at enhancing regenerative outcomes in the aging population.