Emerging role of NEDD8-mediated neddylation in age-related metabolic diseases

Aging in humans is associated with abdominal distribution and remodeling of body fat and a parallel gradual increase in the prevalence of metabolic diseases such as obesity, type 2 diabetes mellitus and fatty liver disease, as well as the risk of developing metabolic complications. Current treatments might be improved by understanding the detailed mechanisms underlying the onset of age-related metabolic disorders. Neddylation, a post-translational modification that adds the ubiquitin-like protein NEDD8 to substrate proteins, has recently been linked to age-related metabolic diseases, opening new avenues of investigation and raising a potential target for treatment of these diseases. In this review, we will focus on the potential role of NEDD8-mediated neddylation in age-related metabolic dysregulation, insulin resistance, obesity, type 2 diabetes mellitus and fatty liver. We propose that alterations in NEDD8-mediated neddylation contribute to triggering insulin resistance and the development of age-related metabolic dysregulation, thus highlighting NEDD8 as a promising therapeutic target for preventing age-related metabolic diseases.