SHH and bone disorder: To unravel the upstream regulatory mechanisms responsible for age-related Shh downregulation in TES and the compromised GMT, we focused on NAD+ metabolism, a known hallmark of aging linked to skeletal diseases.32 Both serum and supernatant medium of SCs NAD+ levels in aged mice were substantially lower than those in younger mice (P < 0.01, n = 5) (Fig. 5h).