Aging mechanisms in bone
- 4 July 2012
- journal article
- Published by Portico in BoneKEy Reports
- Vol. 1 (7)
- https://doi.org/10.1038/bonekey.2012.102
Abstract
Advancing age and loss of bone mass and strength are closely linked. Elevated osteoblast and osteocyte apoptosis and decreased osteoblast number characterize the age-related skeletal changes in humans and rodents. Similar to other tissues, oxidative stress increases in bone with age. This article reviews current knowledge on the effects of the aging process on bone and its cellular constituents, with particular emphasis on the role of reactive oxygen species (ROS). FoxOs, sirtuins and the p53/p66shc signaling cascade alter osteoblast number and bone formation via ROS-dependent and -independent mechanisms. Specifically, activation of the p53/p66shc signaling increases osteoblast/osteocyte apoptosis in the aged skeleton and decreases bone mass. FoxO activation in osteoblasts prevents oxidative stress to preserve skeletal homeostasis. However, while defending against stress FoxOs bind to β-catenin and attenuate Wnt/T-cell cell factor transcriptional activity and osteoblast generation. Thus, pathways that impact longevity and several diseases of ageing might also contribute to age-related osteoporosis.Keywords
This publication has 93 references indexed in Scilit:
- Osteocyte RANKL: New insights into the control of bone remodelingJournal of Bone and Mineral Research, 2012
- Mitochondrial Complex III ROS Regulate Adipocyte DifferentiationCell Metabolism, 2011
- Unraveling the role of FoxOs in bone—Insights from mouse modelsBone, 2011
- Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy MetabolismCell, 2010
- Insulin Receptor Signaling in Osteoblasts Regulates Postnatal Bone Acquisition and Body CompositionCell, 2010
- Effects of chronic estrogen treatment on modulating age-related bone loss in female miceJournal of Bone and Mineral Research, 2010
- FoxO1 Is a Positive Regulator of Bone Formation by Favoring Protein Synthesis and Resistance to Oxidative Stress in OsteoblastsCell Metabolism, 2010
- FoxO-Mediated Defense against Oxidative Stress in Osteoblasts Is Indispensable for Skeletal Homeostasis in MiceCell Metabolism, 2010
- Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life SpanCell Metabolism, 2008
- Trends in oxidative aging theoriesFree Radical Biology & Medicine, 2007