SIRT1 and chronic obstructive pulmonary disease: SIRT6 plays an important role in the regulation of autophagy in COPD.591 For example, reduced SIRT6 expression level is associated with COPD development through enhancement of cellular senescence created by insufficient autophagy during CS exposure.601 SIRT6 overexpression weakens autophagy via IGF–Akt–mTOR signaling.601 Similar to SIRT1, reduced SIRT6 level is also implicated in COPD.602 Therefore, SIRT6 deficiency might contribute to the development of COPD.