Aging causes bone to deteriorate, as is the case for all types of tissue in our bodies. This open access paper reviews what is known of the higher level mechanisms involved in bone aging, but it remains the case that little work is done to link these mechanisms with specific forms of age-related damage, such as those outlined in the SENS research and development proposals. Most researchers work towards linking specific outcomes in aging to the secondary results of damage, such as changes in gene expression and rising levels of oxidative stress:
With advancing age, the amount of bone resorbed by the osteoclasts is not fully restored with bone deposited by the osteoblasts and this imbalance leads to bone loss. Thus, aging and osteoporosis are intimately linked.
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.