학술논문
Angiotensin‐converting enzyme 2 deficiency accelerates and angiotensin 1‐7 restores age‐related muscle weakness in mice
Document Type
article
Author
Hikari Takeshita; Koichi Yamamoto; Satoko Nozato; Masao Takeda; So‐ichiro Fukada; Tadakatsu Inagaki; Hirotsugu Tsuchimochi; Mikiyasu Shirai; Yoichi Nozato; Taku Fujimoto; Yuki Imaizumi; Serina Yokoyama; Motonori Nagasawa; Go Hamano; Kazuhiro Hongyo; Tatsuo Kawai; Hiroko Hanasaki‐Yamamoto; Shuko Takeda; Toshimasa Takahashi; Hiroshi Akasaka; Norihisa Itoh; Yoichi Takami; Yasushi Takeya; Ken Sugimoto; Hironori Nakagami; Hiromi Rakugi
Source
Journal of Cachexia, Sarcopenia and Muscle, Vol 9, Iss 5, Pp 975-986 (2018)
Subject
Language
English
ISSN
2190-6009
2190-5991
2190-5991
Abstract
Abstract Background A pharmacologic strategy for age‐related muscle weakness is desired to improve mortality and disability in the elderly. Angiotensin‐converting enzyme 2 (ACE2) cleaves angiotensin II into angiotensin 1‐7, a peptide known to protect against acute and chronic skeletal muscle injury in rodents. Since physiological aging induces muscle weakness via mechanisms distinct from other muscle disorders, the role of ACE2‐angiotensin 1‐7 in age‐related muscle weakness remains undetermined. Here, we investigated whether deletion of ACE2 alters the development of muscle weakness by aging and whether angiotensin 1‐7 reverses muscle weakness in older mice. Methods After periodic measurement of grip strength and running distance in male ACE2KO and wild‐type mice until 24 months of age, we infused angiotensin 1‐7 or vehicle for 4 weeks, and measured grip strength, and excised tissues. Tissues were also excised from younger (3‐month‐old) and middle‐aged (15‐month‐old) mice. Microarray analysis of RNA was performed using tibialis anterior (TA) muscles from middle‐aged mice, and some genes were further tested using RT‐PCR. Results Grip strength of ACE2KO mice was reduced at 6 months and was persistently lower than that of wild‐type mice (p