Zhu Zhenhua, Li Linsen, Ye Youqiong, Zhong Qing
Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell Oncol (Dordr). 2024 Dec;47(6):2183-2199. doi: 10.1007/s13402-024-00996-w. Epub 2024 Oct 16.
Autophagy is frequently observed in tissues during the aging process, yet the tissues most strongly correlated with autophagy during aging and the underlying regulatory mechanisms remain inadequately understood. The purpose of this study is to identify the tissues with the highest correlation between autophagy and aging, and to explore the functions and mechanisms of autophagy in the aging tissue microenvironment.
Integrated bulk RNA-seq from over 7000 normal tissue samples, single-cell sequencing data from blood samples of different ages, more than 2000 acute myeloid leukemia (AML) bulk RNA-seq, and multiple sets of AML single-cell data. The datasets were analysed using various bioinformatic approaches.
Blood tissue exhibited the highest positive correlation between autophagy and aging among healthy tissues. Single-cell resolution analysis revealed that in aged blood, classical monocytes (C. monocytes) are most closely associated with elevated autophagy levels. Increased autophagy in these monocytes correlated with a higher proportion of C. monocytes, with hypoxia identified as a crucial contributing factor. In AML, a representative myeloid blood disease, enhanced autophagy was accompanied by an increased proportionof C. monocytes. High autophagy levels in monocytes are associated with pro-inflammatory gene upregulation and Reactive Oxygen Species (ROS) accumulation, contributing to tissue aging.
This study revealed that autophagy is most strongly correlated with aging in blood tissue. Enhanced autophagy levels in C. monocytes demonstrate a positive correlation with increased secretion of pro-inflammatory factors and elevated production of ROS, which may contribute to a more rapid aging process. This discovery underscores the critical role of autophagy in blood aging and suggests potential therapeutic targets to mitigate aging-related health issues.
自噬在衰老过程的组织中经常被观察到，但衰老过程中与自噬最密切相关的组织及其潜在的调控机制仍未得到充分了解。本研究的目的是确定自噬与衰老之间相关性最高的组织，并探索自噬在衰老组织微环境中的功能和机制。
整合来自7000多个正常组织样本的批量RNA测序、不同年龄血液样本的单细胞测序数据、2000多个急性髓系白血病（AML）批量RNA测序以及多组AML单细胞数据。使用各种生物信息学方法对数据集进行分析。
在健康组织中，血液组织在自噬与衰老之间表现出最高的正相关性。单细胞分辨率分析显示，在老年血液中，经典单核细胞（C.单核细胞）与自噬水平升高最为密切相关。这些单核细胞中自噬的增加与C.单核细胞比例的升高相关，其中缺氧被确定为一个关键因素。在AML（一种典型的髓系血液疾病）中，自噬增强伴随着C.单核细胞比例的增加。单核细胞中高自噬水平与促炎基因上调和活性氧（ROS）积累相关，导致组织衰老。
本研究表明，自噬与血液组织衰老的相关性最强。C.单核细胞中自噬水平的增强与促炎因子分泌增加和ROS产生升高呈正相关，这可能导致更快速的衰老过程。这一发现强调了自噬在血液衰老中的关键作用，并提示了减轻与衰老相关健康问题的潜在治疗靶点。
