衰老会导致机体各个器官的功能下降但会被热量限制所缓解。甲状腺作为一种关键的内分泌器官，参与了机体的免疫和代谢等重要生物学过程的调控。然而，目前的研究大多集中在甲状腺激素相关的生理生化方向，还缺乏甲状腺单细胞水平的资源。本研究分离6月龄自由喂食的年轻小鼠、24月龄自由喂食的衰老小鼠和24月龄70%热量限制的衰老小鼠的甲状腺进行单细胞测序，首次建立了衰老和热量限制小鼠甲状腺的单细胞图谱。研究发现，热量限制在基因表达、转录因子网络以及细胞通讯等多层面延缓衰老。从器官水平和细胞亚群水平的分析均显示，热量限制可以通过挽救免疫和代谢相关的基因表达来影响衰老过程，并重塑了衰老过程的转录因子网络，而CCCTC结合因子（CCCTC binding factor，CTCF）可能是调控许多挽救基因的关键转录因子。此外，热量限制还通过改变免疫细胞和血管内皮细胞的相互作用影响衰老。总而言之，本研究从单细胞水平解析了甲状腺衰老与热量限制的可能机制，并进一步验证了免疫是衰老的关键因素。

Aging leads to a functional decline in various organs which can be alleviated by caloric restriction (CR). The thyroid gland, as a crucial endocrine organ, regulates many important biological processes such as immunity and metabolism. However, recent research about thyroid largely focuses on the physiological and biochemical aspects related to thyroid hormones while lacks of resources at single-cell level. Here, we isolated thyroid glands from 6-month-old ad libitum (AL) young mice, 24-month-old AL mice, and 24-month-old old mice subjected to 70% CR for single-cell sequencing (scRNA-seq) and built a single-cell atlas of the mouse thyroid undergoing aging and CR. CR alleviated aging at multiple levels, including gene expression, transcription factor (TF) networks, and cell-cell communication patterns. Analysis at both the organ level and cell type level demonstrated that CR influenced the aging process by rescuing immune and metabolic gene expression while reshaping TF networks. We found that CCCTC binding factor (CTCF) may be a key transcription factor regulating many of these rescued genes. CR also influenced aging by altering the interactions between immune cells and vascular endothelial cells (VECs). In summary, we elucidates the potential mechanisms of thyroid aging and CR at the single-cell level, and further validates that immunity is a crucial factor in aging and CR.