This applies, for instance, to normal human brain aging (in which the autophagy markers Atg5, Atg7, and Beclin1 are downregulated) to insulin resistance and metabolic syndrome (in which Sirtuin1 is downregulated) or to osteoarthritis, where a downregulation of ULK1, Beclin1, and LC3 occurs [156, 157]. The gene discussed is BECN1; the disease is metabolic syndrome.