Age-related bone loss tied to STING signaling in marrow immune cells
A study in Advanced Science reports that the STING immune signaling pathway becomes more active in bone marrow macrophages as mice age. Removing STING in bone marrow cells lowered bone density in young mice but protected older mice from bone loss. The work also links senescent bone marrow fat cells, and the protein DPP4 they release, to STING activation and inflammation.
The study used mice with STING removed specifically from bone marrow cells. In younger animals, this loss unexpectedly weakened bones, while in older animals it guarded against age-related bone decline. This age-dependent reversal suggests STING's role in skeletal maintenance changes over the lifespan.
Older bone marrow fat cells, or adipocytes, were found to drive STING activity in young macrophages. When these fat cells become senescent, they release DPP4, which promotes inflammation and bone loss. The pathway also lowers NAD+, a molecule needed for metabolism and DNA repair, impairing stem cells that build bone.
Because bone loss and osteoporosis affect many aging people, targeting STING or DPP4 could eventually offer new ways to protect skeletal health. Older adults, especially those with frailty or fracture risk, may benefit most if such approaches translate from mice to humans. However, the findings remain preclinical, so any societal impact would depend on further safety and efficacy research. A treatment that modulates immunity would need careful balancing, since the same pathway helps defend against infection and cancer.