Hematoxylin and Eosin stained mid-coronal sections of lumbar intervertebral disc from one-week-old (A) and one-year-old mice show age-related structural changes. In the young, healthy disc, the Hh signaling pathway is turned on by Shh ligand produced by NP cells, resulting in the activation of the signal transduction pathway as illustrated in (C). Shh expression reduces in NP cells with age, and thus the Hh signaling pathway in (B) would be turned off, as shown in (D). Scale bar in (A) and (B) is 200 µm. NP=nucleus pulposus; AF=annulus fibrosus; EP=end plate