Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria.

To determine the role of reactive oxygen species in mammalianlongevity, we generated transgenic mice that overexpress human catalaselocalized to the peroxisome, the nucleus, or mitochondria (MCAT). Medianand maximum life spans were maximally increased (averages of 5 monthsand 5.5 months, respectively) in MCAT animals. Cardiac pathology andcataract development were delayed, oxidative damage was reduced, H[sub2]O[sub 2] production and H[sub 2]O[sub 2]-induced aconitaseinactivation were attenuated, and the development of mitochondrialdeletions was reduced. These results support the free radical theory ofaging and reinforce the importance of mitochondria as a source of theseradicals. [ABSTRACT FROM AUTHOR]