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

American Association for the Advancement of Science (AAAS) - Tập 308 Số 5730 - Trang 1909-1911 - 2005
Samuel E. Schriner1,2,3,4,5, Nancy J. Linford1,2,3,4,5, George M. Martin1,2,3,4,5, Piper M. Treuting1,2,3,4,5, Charles E. Ogburn1,2,3,4,5, Mary J. Emond1,2,3,4,5, Pınar Coşkun1,2,3,4,5, Warren Ladiges1,2,3,4,5, Norman S. Wolf1,2,3,4,5, Holly Van Remmen1,2,6,3,5, Douglas C. Wallace1,2,3,4,5, Peter S. Rabinovitch1,2,3,4,5
1Center for Molecular and Mitochondrial Medicine and Genetics, Department of Biological Chemistry and Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, CA 92697, USA.
2Department of Biostatistics, University of Washington, Seattle, WA 91895, USA.
3Department of Comparative Medicine, University of Washington, Seattle, WA 91895, USA.
4Department of Genome Sciences, University of Washington, Seattle, WA 91895, USA.
5Department of Pathology, University of Washington, Seattle, WA 91895, USA.
6Department of Cellular and Structural Biology, University of Texas Health Sciences Center at San Antonio, San Antonio, TX 78229, USA.

Tóm tắt

To determine the role of reactive oxygen species in mammalian longevity, we generated transgenic mice that overexpress human catalase localized to the peroxisome, the nucleus, or mitochondria (MCAT). Median and maximum life spans were maximally increased (averages of 5 months and 5.5 months, respectively) in MCAT animals. Cardiac pathology and cataract development were delayed, oxidative damage was reduced, H 2 O 2 production and H 2 O 2 -induced aconitase inactivation were attenuated, and the development of mitochondrial deletions was reduced. These results support the free radical theory of aging and reinforce the importance of mitochondria as a source of these radicals.

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We thank L. Loeb B. Preston and E. Ruiz-Pesini for insightful comments; S. Chen S. Tsang S. Knoblaugh R. Mangalindan and N. Hudson for technical contributions; and C. Epstein for SOD1-overexpressing animals. Supported by NIH grants AG001751 ES07033 and AG13280.

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American Association for the Advancement of Science (AAAS)

Tập 308 Số 5730

1909-1911

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