Population aging is becoming an epidemic worldwide, resulting in increased incidence and prevalence of a series of age-related metabolic disorders, including obesity, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Recent evidence suggests that tissue-specific dysregulation of the cytoplasmic degradation system, autophagy could be the main cause of these age-related metabolic disorders, but the underlying mechanisms are poorly understood. In this proposal, by focusing on several important regulators of autophagy, we aim to identify the molecular mechanisms of tissue-specific regulation and roles of autophagy, and this may lead to the development of therapeutic approaches for age-related metabolic disorders. Tissue specific analysis of several autophagy regulators in liver, adipose and pancreas is on-going, while we revealed neuronal function of autophagy regulators is critical to regulate animal aging (Shioda, ^*Nakamura et al., PNAS, 2024). Further studies will get a novel insight into tissue specific regulatory mechanism of autophagy and its roles in age-related metabolic disorders.