BoneKEy Reports | BoneKEy Watch

A genetic link between long life, aging and bone loss


NF-κB signaling is known to maintain normal bone mass by controlling osteoclastogenesis and osteoclast function. Using bisphosphonates or other inhibitors of RANKL, the receptor activator of the NF-κB ligand, can reduce the bone loss that occurs with aging. In this study, Edwards et al. investigated how silent information regulator T1 (SirT1), NF-κB and longevity/aging are connected.

When transgenic mice were bred with a specific SirT1 deletion in osteoclasts and osteoblasts, the animals showed increased bone resorption, reduced bone formation and a consequent decrease in bone mass. Deletion of SirT1 in osteoclasts in vitro stimulated osteoclastogenesis, which could be blocked by pharmacological doses of NF-κB. The absence of SirT1 in osteoblasts led to a reduction in osteoblast differentiation, which was rescued if an NF-κB inhibitor was applied.

The findings strongly suggest that SirT1 is expressed in osteoclasts and osteoblasts and is a genetic determinant of bone mass. SirT1 acts by controlling NF-κB signaling and bone cell differentiation.

Editor’s comment: This study provides important insights into the mechanisms linking aging, longevity and bone loss. It is interesting that enhancement of SirT1 levels by the plant polyphenol resveratrol are needed to maintain stem cell populations and to commit cells towards an osteoblast lineage over adipocyte formation. Resveratrol and its analogues can also suppress NF-κB activity and osteoclast differentiation.

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