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Research Paper|Volume 13, Issue 7|pp 9719—9731

Whole-life body composition trajectory and longevity: role of insulin

Yu-Hsuan Lin1, Shiow-Chwen Tsai1, Sheng-Ju Chuang1,8, M. Brennan Harris2, Kunanya Masodsai1, Pei-Ni Chen1, Chao-Chieh Hsieh1, Theodore Killian8, Chih-Yang Huang3,4,5,6,7, Chia-Hua Kuo1,6
  • 1Laboratory of Exercise Biochemistry, University of Taipei, Taipei 111, Taiwan
  • 2Department of Kinesiology and Health Science, College of William and Mary, Williamsburg, VA 23187, USA
  • 3Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
  • 4Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien 970, Taiwan
  • 5Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan
  • 6Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
  • 7Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan
  • 8De Duve Insitute, Université Catholique de Louvain (UCL), Woluwe-Saint-Lambert B-1200, Brussels, Belgium
* Equal contribution
Received: November 25, 2020Accepted: February 3, 2021Published: March 19, 2021
https://doi.org/10.18632/aging.202727

Copyright: © 2021 Lin 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.

Abstract

The present study assessed the body composition trajectory of rats (N = 96) placed into 5 groups according to lifespan, using dual-energy x-ray absorptiometry every 6 months until end-of-life. A striking linearity between lifespan and bone mass percentage (not absolute bone mass) was observed. Long-lived rats show a higher bone mass percentage with a delayed insulin rise to a similar peak level as short-lived counterparts, followed by insulin declines and bone mass loss. Decreasing insulin after streptozotocin (STZ) injection caused a rapid bone mass loss (-10.5%) with a decreased 5-day survival rate to 35% in old rats (20 months). Insulin replacement to STZ-injected rats completely blocked bone mass loss and increased the survival rate to 71%. Normal old rats (20 months) had faster lean mass loss despite greater myofiber regeneration (centronucleation) compared with the young rats (4 months). Increased CD68+ and CD163+ cell infiltration into insulin-depleted muscle suggests a bone marrow cell exhaustion by aging muscle. Bone produces stem cells and phagocytes to continuously rejuvenate peripheral tissues. Our data suggests that aging and unsustainable life is associated with development of disproportionality between bone and the growing body size, partly due to insulin reversal from hyperinsulinemia during late life.