Similarly, the expression of various proteins required for autophagy induction is reduced in ageing and pathological conditions; for instance, Atg5, Atg7 and BECN1 are downregulated in the normal human aged brain [136], Sirt1 is downregulated in subjects with insulin resistance and metabolic syndrome [153] and ULK1, BECN1 and LC3 are downregulated in osteoarthritis patients [154], suggesting that insufficient autophagy may contribute to the ageing phenotype. This evidence concerns the gene BECN1 and osteoarthritis.