Mouse models used to test the role of reactive oxygen species in aging and age-related chronic diseases

With the development of the technology to generate transgenic and knockout mice in the 1990s, investigators had a powerful tool to directly test the impact of altering a specific gene on a biological process or disease. Over the past three decades, investigators have used transgenic and knockout mouse models, which have altered expression of antioxidant genes, to test the role of oxidative stress/damage in aging and age-related diseases. In this comprehensive review, we describe the studies using transgenic and knockout mouse models to test the role of oxidative stress/damage in aging (longevity) and three age-related diseases, e.g., sarcopenia, cardiac aging, and Alzheimer's Disease. While longevity was consistently altered only by one transgenic and one knockout mouse model as predicted by the Oxidative Stress Theory of Aging, the incidence/progression of the three age-related diseases (especially Alzheimer's disease) were robustly impacted when the expression of various antioxidant genes was altered using transgenic and knockout mouse models. [Display omitted] •Overexpressing or knocking out most antioxidant genes had little effect on lifespan.•Lifespan was altered by deleting Sod1 or overexpressing catalase in mitochondria.•Overexpressing or knocking out antioxidant genes impacted Alzheimer's disease.•Overexpressing or knocking out antioxidant genes protected heart from stress.•Knocking out antioxidant genes accelerated sarcopenia.