Importantly, the above model (and loss of this protective effect of TRAF3 in the cKO mice, with associated osteoporosis) is supported by significantly lower TRAF3 protein levels in bone from older adults than from children and in bone and BM from old than from young mice, associated with increased levels of active TGFβ1 in the BM of older mice and in the bone of older humans. The gene discussed is TRAF3; the disease is osteoporosis.