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Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.93 Figure 4 Clock gene deregulation: a functional link between ageing and OA Figure 4 | Clock gene deregulation: a functional link between ageing and OA. During ageing, circadian rhythms deteriorate, leading to increased propensity to obesity, which is a major risk factor for metabolic osteoarthritis (OA). Disrupted circadian rhythms in old age is also associated with altered diurnal patterns and reduced levels of physical activity, further contributing to OA pathogenesis. Age-related decline of local clock functions within the joint can have more direct detrimental effects on the homeostasis of joint tissues. ANS, autonomic nervous system; HPA axis, hypothalamic–pituitary–adrenal axis; HPT axis, hypothalamic–pituitary–thyroid axis. Berenbaum, F. & Meng, Q. –J. (2016) The brain–joint axis in osteoarthritis: nerves, circadian clocks and beyond Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2016.93