Extension of mouse lifespan by overexpression of catalase
Tóm tắt
The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H2O2), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H2O2 production and H2O2-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H2O2 in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.
Tài liệu tham khảo
Armstrong JS, Whiteman M, Yang H, Jones DP (2004) The redox regulation of intermediary metabolism by a superoxide-aconitase rheostat. BioEssays 26:894–900
Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581
Chen XJ, Wang X, Kaufman BA, Butow RA (2005) Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 307:714–717
Enesco HE, Verdone-Smith C (1980) Alpha-tocopherol increases lifespan in the rotifer Philodina. Exp Gerontol 15:335–338
Finch CE (1990) Longevity, senescence, and the genome. University of Chicago Press, Chicago
Gardner PR, Fridovich I (1992) Inactivation-reactivation of aconitase in Escherichia coli. A sensitive measure of superoxide radical. J Biol Chem 267:8757–8763
Gentry A, Venkatachalam S (2005) Complicating the role of p53 in aging. Aging Cell 4:157–160
Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine. Oxford University Press, New York
Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 2:298–300
Harman D (1968) Free radical theory of aging: effect of free radical reaction inhibitors on the mortality rate of male LAF mice. J Gerontol 23:476–482
Ho YS, Xiong Y, Ma W, Spector A, Ho DS (2004) Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 279:32804–32812
Huang TT, Carlson E, Gillespie AM, Shi Y, Epstein CJ (2000) Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol Ser A Biol Sci Med Sci 55:B5–B9
Imai H, Nakagawa Y (2003) Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells. Free Radic Biol Med 34:145–169
Kwong LK, Mockett RJ, Bayne AC, Orr WC, Sohal RS (2000) Decreased mitochondrial hydrogen peroxide release in transgenic Drosophila melanogaster expressing intramitochondrial catalase. Arch Biochem Biophys 383:303–308
Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90:8905–8909
Liang LP, Patel M (2004) Mitochondrial oxidative stress and increased seizure susceptibility in Sod2(-/+) mice. Free Radic Biol Med 36:542–554
Lin YJ, Seroude L, Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282:943–946
Maulik N, Das DK (2002) Redox signaling in vascular angiogenesis. Free Radic Biol Med 33:1047–1060
Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE et al (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289:1567–1569
Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP et al (1999) The p66shc adaptor protein controls oxidative stress response and lifespan in mammals. Nature 402:309–313
Miquel J, Economos AC (1979) Favorable effects of the antioxidants sodium and magnesium thiazolidine carboxylate on the vitality and life span of Drosophila and mice. Exp Gerontol 14:279–285
Mitsui A, Hamuro J, Nakamura H, Kondo N, Hirabayashi Y, Ishizaki-Koizumi S, Hirakawa T, Inoue T, Yodoi J (2002) Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span. Antioxid Redox Signal 4:693–696
Mockett RJ, Bayne AC, Kwong LK, Orr WC, Sohal RS (2003) Ectopic expression of catalase in Drosophila mitochondria increases stress resistance but not longevity. Free Radic Biol Med 34:207–217
Orr WC, Sohal RS (1992) The effects of catalase gene overexpression on lifespan and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 297:35–41
Orr WC, Sohal RS (1993) Effects of Cu-Zn superoxide dismutase overexpression of lifespan and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 301:34–40
Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263:1128–1130
Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19:171–174
Percy ME (1984) Catalase: an old enzyme with a new role? Can J Biochem Cell Biol 62:1006–1014
Radi R, Turrens JF, Chang LY, Bush KM, Crapo JD, Freeman BA (1991) Detection of catalase in rat heart mitochondria. J Biol Chem 266:22028–22034
Rattan SI (2004) Aging, anti-aging, and hormesis. Mech Ageing Dev 125:285–289
Reth M (2002) Hydrogen peroxide as second messenger in lymphocyte activation. Nat Immunol 3:1129–1134
Schisler NJ, Singh SM (1991) A quantitative genetic analysis of tissue-specific catalase activity in Mus musculus. Biochem Genet 29:65–89
Schriner SE, Smith AC, Dang NH, Fukuchi K, Martin GM (2000) Overexpression of wild-type and nuclear-targeted catalase modulates resistance to oxidative stress but does not alter spontaneous mutant frequencies at APRT. Mutat Res 449:21–31
Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M et al (2005) Extension of murine lifespan by overexpression of catalase targeted to mitochondria. Science 308:1909–1911
Simon HU, Haj-Yehia A, Levi-Schaffer F (2000) Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 5:415–418
Sun J, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the lifespan of adult Drosophila melanogaster. Genetics 161:661–672
Townsend DM, Tew KD, Tapiero H (2003) The importance of glutathione in human disease. Biomed Pharmacother 57:145–155
Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE et al (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:417–423
Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H et al (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415:45–47
Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR et al (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16:29–37
Yan LJ, Levine RL, Sohal RS (1997) Oxidative damage during aging targets mitochondrial aconitase. Proc Natl Acad Sci USA 94:11168–11172