Mouse Life-Span Increases 20% with Overexpression of Mitochondrial Catalase

Peter S. Rabinovitch, MD, Ph.D.
University of Washington
P30ES07033

Background: The free radical theory of aging refers to the role reactive oxygen species play in aging processes. Reactive oxygen molecules oxidize and damage biological molecules and cause decline in the function of cells, tissues, and organ systems that eventually lead to death. The cumulative effect of the damage is thought to play an important role in the physiological declines associated with aging as well as in a diversity of diseases associated with aging including cataracts, neurological diseases, atherosclerosis, and cancer. Mitochondria are the cellular organelles responsible for energy generation and are the site of formation of most reactive oxygen molecules. Whether life-span can be extended by increasing antioxidant defenses is controversial despite some encouraging evidence from invertebrate animal models. To test this theory in higher organisms, these investigators developed three transgenic mice that overexpress the antioxidant enzyme, catalase, specifically targeted to peroxisomes, the nucleus, and mitochondria respectively.

Advance: In the transgenic animals that have catalase targeted to their mitochondria, life-span was extended by about 5 months or about 20%. Catalase activities were increased in the heart, skeletal muscle, and brain tissue. In fact, cardiac levels of catalase activity were 50 times higher in the transgenic animals than wild-type mice. The life-span extension in these animals was accomplished without deleterious side effects such as those seen in other studies using caloric restriction and other models of delayed aging. Cardiac disease and cataract development were delayed in these animals, and oxidative damage and the production of reactive oxygen molecules were reduced.

Implications: These results support the theory that free radical and reactive oxygen molecules generated in the mitochondria are very important in aging processes. It is too early to say that human lives could be extended by the administration of antioxidant compounds; however, this study has produced exciting results with implications for longevity, possible new treatments for aging related illnesses, and healthier aging.

Citation: Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005 Jun 24;308(5730):1909-11.