Humanin and Its Pathophysiological Roles in Aging: A Systematic Review

Simple Summary Humanin is a small mitochondrial-derived peptide still under study, with a number of potential therapeutic applications for various age-related diseases. It plays an important role in the body against several pathophysiological conditions; for instance, humanin has been shown to exert neuroprotective effects, which may make it a promising therapeutic candidate for Alzheimer's and Parkinson's disease. Moreover, it can help reduce inflammation and oxidative stress, thus interfering with the development of cardiovascular conditions and autoimmune diseases. Humanin also helps maintain the proper functioning of mitochondria, the dysfunction of which can contribute to a number of health problems, including neurodegenerative diseases and metabolic disorders, such as diabetes and obesity. It has been shown to improve glucose metabolism and insulin sensitivity in animal models. Treatment with humanin on mice is able to increase both their lifespan and health span. The mechanisms behind the protective effects of humanin in different diseases are slowly being unveiled and appear to be connected with autophagy and cytoprotective activity. Background: Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. These conditions play an essential role in aging and significantly contribute to the development of age-related complications. Humanin is a mitochondrial-derived peptide (MDP), encoded by mitochondrial DNA, playing a cytoprotective role to preserve mitochondrial function and cell viability under stressful and senescence conditions. For these reasons, humanin can be exploited in strategies aiming to counteract several processes involved in aging, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to aging and disease: Senescence appears to be involved in the decay in organ and tissue function, it has also been related to the development of age-related diseases, such as cardiovascular conditions, cancer, and diabetes. In particular, senescent cells produce inflammatory cytokines and other pro-inflammatory molecules that can participate to the development of such diseases. Humanin, on the other hand, seems to contrast the development of such conditions, and it is also known to play a role in these diseases by promoting the death of damaged or malfunctioning cells and contributing to the inflammation often associated with them. Both senescence and humanin-related mechanisms are complex processes that have not been fully clarified yet. Further research is needed to thoroughly understand the role of such processes in aging and disease and identify potential interventions to target them in order to prevent or treat age-related conditions. Objectives: This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, humanin, aging, and disease.