The past decade has witnessed many advances in the understanding of
sirtuin biology and related regulatory circuits supporting the capacity of these
proteins to serve as energy-sensing molecules that contribute to healthspan in various tissues, including articular cartilage. Hence, there has been a significant increase in new investigations that aim to elucidate the mechanisms of
sirtuin function and their roles in cartilage biology, skeletal development, and pathologies such as
osteoarthritis (OA),
rheumatoid arthritis (RA), and
intervertebral disc degeneration (IVD). The majority of the work carried out to date has focused on
SIRT1, although SIRT6 has more recently become a focus of some investigations. In vivo work with transgenic mice has shown that
Sirt1 and Sirt6 are essential for maintaining cartilage homeostasis and that the use of
sirtuin-activating molecules such as
resveratrol may have beneficial effects on cartilage anabolism. Current thinking is that
SIRT1 exerts positive effects on cartilage by encouraging chondrocyte survival, especially under stress conditions, which may provide a mechanism supporting the use of
sirtuin small-molecule activators (STACS) for future therapeutic interventions in OA and other degenerative pathologies of joints, especially those that involve articular cartilage.