BECN1 and osteoarthritis: For instance, several proteins that are required for autophagy (Atg5, Atg7 and Beclin 1) are downregulated in normal human brain ageing [53] and in osteoarthritis (ULK1, Beclin 1 and LC3) [54], while knock-in of an activated form of Beclin 1 delays the onset of cardiac and renal fibrosis in normally ageing C57/BL6 mice, and even rescues the short lifespan of Klotho mutant mice [55].