Protein Homeostasis and Antiaging Medicine: Posttranslational Modification of Proteins and Antiaging

It is known that various factors such as diet, lifestyle habits, and stress are complexly involved in the causes of aging and disease, and among them, the body’s “rusting” or “oxidation” is considered one factor. The body generates energy using oxygen, but in the process, reactive oxygen species (ROS) are constantly produced as by-products. Normally, ROS are removed by antioxidant molecules in the body, but an increase in production or a decrease in removal ability can cause oxidative modifications of proteins, lipids, and DNA in the body, leading to many aging-related diseases such as cataracts, arteriosclerosis, and diabetes. In particular, oxidative modification of proteins not only reduces the original function of the protein, but also forms a new structure called an oxidation-specific epitope on the protein molecule, forming endogenous antigens called damage-associated molecular patterns (DAMPs). Excessive accumulation of DAMPs induces inflammation and is involved in diseases including aging and lifestyle-related diseases. As a defense system against such ROS-induced disruption of homeostasis (oxidative stress), food-derived antioxidants such as vitamin C, vitamin E, polyphenols, and carotenoids have long been attracting attention. In particular, the antioxidant properties of vitamin C have been reported to be important in antiaging. Unlike humans, mice can synthesize vitamin C in the body, but it has been reported that mice lacking the vitamin C synthesis enzyme show symptoms similar to aging and have a short lifespan when fed a low vitamin C diet [1]. On the other hand, natural antibodies play an important role in the removal of DAMPs. Natural antibodies are antibodies that are constantly produced mainly from B-1 cells even without specific antigen stimulation, and function as an existing immediate defense system to quickly counteract pathogens and viruses. Recently, the functionality of natural antibodies that recognize endogenous antigens, which are self-molecules, has been attracting attention, and it has been shown that the removal of DAMPs by natural antibodies improves inflammatory responses and arteriosclerosis [2].