IBMS BoneKEy | Perspective
Aging and oxidative stress: A new look at old bone
Maria Almeida
DOI:10.1138/20100467
Abstract
Advancing age is a major contributor to a decline of bone mass and strength and, consequently, a rise in the incidence of bone fractures. Skeletal aging in a murine model closely recapitulates age-related skeletal changes in humans, including decreased osteoblast number as well as decreased bone mass and strength and is associated with increased oxidative stress. This Perspective reviews what is known about the effects of the aging process on bone and its cellular constituents. Specifically, it discusses how pathways activated by oxidative stress can contribute to the decrease in osteoblast number and bone formation that are the hallmarks of involutional osteoporosis. Activation of the p53/p66shc signaling cascade in the skeleton by reactive oxygen species increases osteoblast/osteocyte apoptosis. On the other hand, reactive oxygen species stimulate the FoxO family of transcription factors that defend cells against oxidative stress. In line with this, loss of FoxO function in the skeleton increases oxidative stress and decreases bone mass. Conversely, gain of FoxO function specifically in osteoblasts decreases oxidative stress and increases bone mass. This Perspective also reviews the potential contribution of loss of sex steroids, glucocorticoids, as well as oxidized lipids to oxidative stress and skeletal involution.
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