蛋白质营养不良 (PM) 在老年人中很常见，但衰老和 PM 如何影响造血功能尚不完全清楚。本研究旨在评估衰老和 PM 如何影响骨髓 (BM) 间充质干细胞 (MSC) 的造血调节功能。用正常蛋白质或低蛋白质饮食喂养年轻和老年雄性C57BL/6J小鼠，并评估其营养、生化和血液学参数。对 BM MSC 进行了表征，并对其分泌组、基因表达、自噬、活性氧产生 (ROS) 和 DNA 双链断裂进行了评估。使用体外和体内模型测定 MSC 对造血的调节。最后，在用 C1498 细胞系的白血病细胞攻击后，评估了小鼠的 BM 侵袭性和存活率。衰老和 PM 会改变生化参数，从而改变外周血和 BM 免疫表型。 MSC 自噬受到衰老以及 ROS 和 DNA 双链断裂频率的影响。关于 MSC 的分泌组，PM 和衰老影响 CXCL12、IL-6 和 IL-11 的产生。衰老和 PM 上调 Akt1 和 PPAR-γ，同时下调 MSC 中的 Cdh2 和 Angpt-1。老化的 MSC 增加了 C1498 细胞的增殖，同时降低了其集落形成潜力。 PM 和衰老降低了小鼠的存活率，并且营养不良导致 C1498 细胞在骨髓中积累。最后，衰老和/或 PM MSC 在 C1498 细胞中上调 Sox2、Nanog、Pou5f1 和 Akt1 的表达，同时下调 Cdkn1a 的表达。衰老和 PM 共同诱导 BM MSC 的细胞内在变化，创造一个改变造血细胞群调节并有利于恶性细胞发展的环境。版权所有 © 2023。由 Elsevier Inc. 出版。

Protein malnourishment (PM) is common among the elderly, but how aging and PM impact hematopoiesis is not fully understood. This study aimed to assess how aging and PM affect the hematopoietic regulatory function of bone marrow (BM) mesenchymal stem cells (MSCs). Young and aged male C57BL/6J mice were fed with normoproteic or hypoproteic diets and had their nutritional, biochemical and hematological parameters evaluated. BM MSCs were characterized and had their secretome, gene expression, autophagy, reactive oxygen species production (ROS) and DNA double-stranded breaks evaluated. The modulation of hematopoiesis by MSCs was assayed using in vitro and in vivo models. Lastly, BM invasiveness and mice survival were evaluated after being challenged with leukemic cells of the C1498 cell line. Aging and PM alter biochemical parameters, changing the peripheral blood and BM immunophenotype. MSC autophagy was affected by aging and the frequencies for ROS and DNA double-stranded breaks. Regarding the MSCs' secretome, PM and aging affected CXCL12, IL-6 and IL-11 production. Aging and PM upregulated Akt1 and PPAR-γ while downregulating Cdh2 and Angpt-1 in MSCs. Aged MSCs increased C1498 cell proliferation while reducing their colony-forming potential. PM and aging lowered mice survival, and malnourishment accumulated C1498 cells at the BM. Finally, aged and/or PM MSCs upregulated Sox2, Nanog, Pou5f1, and Akt1 expression while downregulating Cdkn1a in C1498 cells. Together, aging and PM can induce cell-intrinsic shifts in BM MSCs, creating an environment that alters the regulation of hematopoietic populations and favoring the development of malignant cells.Copyright © 2023. Published by Elsevier Inc.