Aging (Albany NY). 2019 Jul 21;11(14):4910-4922. doi: 10.18632/aging.102086.

Fang Y^1,2, Zhu L^1,2, An N¹, Jiang G¹, Qian J¹, Zhao R¹, Yuan N^1,2, Zhang S^1,2, Wang J^1,2.

Author Information

¹Hematology Center of Cyrus Tang Medical Institute, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology, State Key Laboratory of Radiation Medicine and Radioprotection, Soochow University School of Medicine, Suzhou 215123, China.

²Research Center for Non-medical Healthcare of Soochow University and Beijing Yaozhongtang, Cyrus Tang Medical Institute, Soochow University School of Medicine, Suzhou 215123, China.

Abstract

Autophagy has been well studied in regulating aging; however, the impact of autophagy in one organ on the aging of other organs has not been documented. In this study, we used a mouse model with deletion of an autophagy-essential gene Atg7 in hematopoietic system to evaluate the intrinsic role of hematopoietic autophagy on the aging of non-hematopoietic organs. We found that autophagy defect in hematopoietic system causes growth retardation and shortened lifespan, along with aging-like phenotypes including hypertrophic heart, lung and spleen, but atrophic thymus and reduced bone mineral density at organismal level. Hematopoietic autophagy defect also causes increased oxidative stress and mitochondrial mass or aging gene expression at cellular level in multiple non-hematopoietic organs. The organ aging in the Atg7-deleted mice was reversed by anatomic connection to wild-type mice with intact blood autophagy via parabiosis, but not by injection of blood cell-free plasma. Our finding thus highlights an essential role of hematopoietic autophagy for decelerating aging in non-hematopoietic organs.