The application discloses a role of p62 in aging-related disease, such as development of obesity, type 2 diabetes mellitus, non-alcoholic fatty liver, various tumors, increased male mortality, intracellular inclusion named sequestosome, and redox regulation. In particular the application discloses a method of detecting the formation of inclusion bodies in neurodegenerative diseases. The invention further relates to a method of screening for therapeutic agents that disperse the inclusions. Further, transgenic mice containing a mutation in the p62 gene and having a functionally disrupted p62 gene locus are also disclosed.