Mitochondria, as central hubs for energy production and metabolism, are wildly involved in various biological process, and have a complex adaptive mechanism to ensure mitochondrial integrity and function so as to protect themself from mitochondrial damage and aging. Mitochondrial dysfunction has been regarded as one of the key hallmarks of aging process and is linked to the development of numerous age-related diseases. In recent years, there have been many significant discoveries regarding mechanisms of mitochondrial dysfunction. In this review, we systematically discuss the recent findings on the mechanisms of mitochondrial self-protection and dysfunction in the aging process, as well as the impact of mitochondrial dysfunction on aging, and highlight the potential of mitochondrial dysfunction as a new and effective target for anti-aging intervention.