Review Volume 10, Issue 9 pp 2243—2251

Mechanisms of the anti-aging and prolongevity effects of caloric restriction: evidence from studies of genetically modified animals

Shunsuke Hoshino1,2, , Masaki Kobayashi1,2, , Yoshikazu Higami1,2, ,

  • 1 Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8510, Japan
  • 2 Translational Research Center, Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan

Received: July 1, 2018       Accepted: September 10, 2018       Published: September 16, 2018
How to Cite

Copyright: © 2018 Hoshino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


It is widely accepted that caloric restriction (CR) extends lifespan and suppresses various pathophysiological changes. CR suppresses growth hormone/insulin-like growth factor signaling and mechanistic target of rapamycin complex 1 activity, activates sirtuin and enhances mitochondrial redox regulation, but the exact mechanisms are still under debate. In this review, we discuss the mechanisms of CR using evidence from studies of animals that were genetically modified according to recent advances in molecular and genetic technologies, from the viewpoint of the adaptive response hypothesis proposed by Holliday (1989). We then explain the beneficial actions of CR, classified according to whether they operate under feeding or fasting conditions.


CR: caloric restriction; GH/IGF1: growth hormone/insulin-like growth factor 1; WAT: white adipose tissue.