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Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate

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Abstract

What are the mechanisms determining the rate of animal aging? Of the two major classes of endothermic animals, bird species are strikingly long-lived compared to mammals of similar body size and metabolic rate. Thus, they are ideal models to identify longevity-related characteristics not linked to body size or low metabolic rates. Since oxidative stress seems to be related to the basic aging process, we measured specific markers of different kinds of oxidative damage to proteins, like glutamic and aminoadipic semialdehydes (GSA and AASA, specific protein carbonyls), Nɛ-(carboxyethyl)lysine (CEL), Nɛ-(carboxymethyl)lysine (CML), and Nɛ-(malondialdehyde)lysine (MDAL), as well as mitochondrial Complex I content and amino acid and membrane fatty acyl composition, in the brain of short-lived mice (maximum life span [MLSP] 3.5 years) compared with those of long-lived budgerigar ‘parakeets’ (MLSP, 21 years) and canaries (MLSP, 24 years). The brains of both bird species had significantly lower levels of compounds formed as a result of oxidative (GSA and AASA), glycoxidative (CEL and CML), and lipoxidative (CML and MDAL) protein modifications, as well as a lower levels of mitochondrial complex I protein. Although it is known that fatty acid unsaturation is lower in many tissues of long-lived compared to short-lived mammals, this is not true in the particular case of brain. In agreement with this, we also found that the brain tissue of bugerigars and canaries contains no fewer double bonds than that of mice. Amino acid composition analyses revealed that bird proteins have a significantly lower content of His, Leu and Phe, as well as, interestingly, of methionine, whereas Asp, Glu, Ala, Val, and Lys contents were higher than in the mammals. These results, together with those previously described in other tissues of pigeons (MLSP, 35 years) compared to rats (MLSP, 4 years), indicate that oxidative damage to proteins, lipids and mitochondrial DNA are lower in birds (very long-lived species) than in short-lived mammals of similar body size. The lower degree of oxidative modification of bird brain proteins was not due to decreases in the target amino acids (lysine for CEL, CML, MDAL, and AASA; and arg and pro for GSA), since these were present in bird brain proteins at higher or similar levels than in those of mice. These results are consistent with the possibility that decreases in oxidative protein modification are caused at least in part by the low rate of mitochondrial oxygen radical generation in these birds, as in all long-lived homeothermic vertebrates investigated so far.

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Abbreviations

AASA:

aminoadipic semialdehyde

CEL:

Nɛ-(carboxyethyl)lysine

CML:

Nɛ-(carboxymethyl)lysine

DBI:

double bond index

GSA:

glutamic semialdehyde

MDAL:

Nɛ-(malondialdehyde)lysine

MLSP:

maximum life span

PI:

peroxidizability index

PUFA:

polyunsaturated fatty acids

ROS:

reactive oxygen species

SFA:

saturated fatty acids

UFA:

unsaturated fatty acids

References

  • Ahmed MU, Brinkmann-Frye E, Degenhardt TP, Thorpe SR and Baynes JW (1997) Nɛ-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem J 324: 565–570

    CAS  PubMed  Google Scholar 

  • Barja G (2004a) Free radicals and aging. Trends in Neurosci 27: 595–600

    Article  CAS  PubMed  Google Scholar 

  • Barja G (2004b) Aging in vertebrates and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism? Biol Rev 79: 235–251.

    Article  PubMed  Google Scholar 

  • Barja G and Herrero A (1998) Localization at complex I and mechanism of the higher free radical production of brain non-synaptic mitochondria in the short-lived rat than in the longevous pigeon. J Bioenerg Biomembr 30: 235–243.

    Article  CAS  PubMed  Google Scholar 

  • Barja G and Herrero A (2000) Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. FASEB J 14: 312–318

    CAS  PubMed  Google Scholar 

  • Barja G, Cadenas S, Rojas C, Pérez-Campo R and López-Torres M (1994) Low mitochondrial free radical production per unit O2 consumption can explain the simultaneous presence of high longevity and high metabolic rates in birds. Free Rad Res 21: 317–328

    CAS  Google Scholar 

  • Barja G, Portero-Otin M and Pamplona R (2005) Regulation of longevity by mitochondria: role of free radical production and membrane unsaturation. A comparative approach. In: Villarroya F (ed) New Frontiers in Mitochondrial Biogenesis and Disease, pp 155–187. Research Signpost, Kerala, India

    Google Scholar 

  • Baynes JW (2002) The maillard hypothesis on aging: time to focus on DNA. Ann N. Y. Acad Sci USA 959: 360–367

    CAS  Google Scholar 

  • Berlett BS and Stadtman ER (1997) Protein oxidation in aging,disease, and oxidative stress. J Biol Chem 272: 20313– 20316

    Article  CAS  PubMed  Google Scholar 

  • Bielski BHJ, Arudi RL and Sutherland MW (1983) A study of thereactivity of HO2/O2. – with unsaturated fatty acids. J Biol Chem 258: 4759–4761

    CAS  PubMed  Google Scholar 

  • Boveris A and Cadenas E (2000) Mitochondrial production of hydrogen peroxide regulation by nitric oxide and the role of ubisemiquinone. IUBMB Life 50: 245–250

    Article  CAS  PubMed  Google Scholar 

  • Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE and Karlin S (1992) Methods and algorithms for statistical analysis of protein sequences. Proc Natl Acad Sci USA 89: 2002–2006

    CAS  PubMed  Google Scholar 

  • Carp H, Miller F, Hoidal JR and Janoff A (1982) Potential mechanism of emphysema: α1-proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci USA 79: 2041–2045

    CAS  PubMed  Google Scholar 

  • Ciorba MA, Heinemann SH, Weissbach H, Brot N and Hoshi T (1997) Modulation of potassium channel function by methionine oxidation and reduction. Proc Natl Acad Sci USA 94: 9932– 9937

    Article  CAS  PubMed  Google Scholar 

  • Couture P and Hulbert AJ (1995) Membrane fatty acid composition of tissues is related to body mass of mammals. J Membr Biol 148: 27–39

    CAS  PubMed  Google Scholar 

  • Drögue W (2001) Free radicals in the physiological control of cell function. Physiol Rev 82: 47–95.

    Google Scholar 

  • Durand P, Prost M, Loreau N, Lussier-Cacan S and Blacke D (2001) Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest 81: 645–672

    CAS  PubMed  Google Scholar 

  • Farkas T, Kitajka K, Fodor E, Csengeri I, Lahdes E and Yeo YK etal. (2000) Docosahexaenoic acid-containing phospholipid molecular species in brains of vertebrates. Proc Natl Acad Sci USA 97: 6362–6366

    Article  CAS  PubMed  Google Scholar 

  • Ferrari CKB (2004) Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging. Biogerontology 5: 275–289

    Article  CAS  PubMed  Google Scholar 

  • Gredilla R, Barja G and López-Torres M (2001a) Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria, and location of the free radical source. J Bioenerg Biomembr 33: 279–287

    Article  CAS  PubMed  Google Scholar 

  • Gredilla R, Sanz A, López-Torres M and Barja G (2001b) Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart. FASEB J 15: 1589–1591

    CAS  PubMed  Google Scholar 

  • Harman D (1972) The biological clock: the mitochondria? J Am Geriatr Soc 20: 145–147

    CAS  PubMed  Google Scholar 

  • Herrero A and Barja G (1997) Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon. Mech Ageing Dev 98: 95–111

    Article  CAS  PubMed  Google Scholar 

  • Herrero A and Barja G (1998) H2O2 production of heart mitochondria and aging rate are slower in canaries and parakeets than in mice: sites of free radical generation and mechanisms involved. Mech Ageing Dev 103: 133–146

    Article  CAS  PubMed  Google Scholar 

  • Herrero A and Barja G (1999) 8-oxodeoxyguanosine levels in heart and brain mitochondrial and nuclear DNA of two mammals and three birds in relation to their different rates of aging. Aging Clin Exp Res 11: 294–300

    CAS  Google Scholar 

  • Holmes DJ and Austad SN (1995) The evolution of avian senescence patterns: implications for understanding primary aging processes. Amer Zool 35: 307–317

    Google Scholar 

  • Holmes DJ, Flückiger R and Austad SN (2001) Comparative biology of aging in birds: an update. Exp Gerontol 36: 869– 883

    Article  CAS  PubMed  Google Scholar 

  • Knecht KJ, Dunn JA, McFarland KF, McCance DR, Lyons TJ and Thorpe SR et al (1991) Effects of diabetes and aging on Nɛ-(carboxymethyl)lysine levels in human urine. Diabetes 40: 190–196

    CAS  PubMed  Google Scholar 

  • Ku HH and Sohal RS (1993) Comparison of mitochondrial pro-oxidant generation and antioxidant defenses between rat and pigeon: possible basis of variation in longevity and metabolic potential. Mech Ageing Dev 72: 67–76

    Article  CAS  PubMed  Google Scholar 

  • Ku HH, Brunk UT and Sohal RS (1993) Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Rad Biol Med 15: 621– 627

    Article  CAS  PubMed  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680– 685

    Article  CAS  PubMed  Google Scholar 

  • Mitsui A, Hamuro J, Nakamura H, Kondo N, Hirabayashi Y and Ishizaki-Koizumi S et al (2002) Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span. Antiox Redox Signal 4: 693–696

    CAS  Google Scholar 

  • Mori N and Hirayama K (2004) Effect of long-term excessive l-methionine consumption on transferrin receptor abundance and mitochondrial H2O2 generation in rat liver. J Health Sci 50: 277–285

    Article  CAS  Google Scholar 

  • Moskovitz J, Bar-Noy S, Williams WM, Requena J, Berlett BS and Stadtman ER (2001) Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proc Natl Acad Sci USA 98: 12920–12925

    Article  CAS  PubMed  Google Scholar 

  • Nakamura H, Mitsui A and Yodoi J (2002) Thioredoxin overexpression in transgenic mice. Methods Enzymol 347: 436– 440

    CAS  PubMed  Google Scholar 

  • Ninomiya T, Kiyohara Y, Kubo M, Tanizaki Y, Tanak K and Okubo K et al (2004) Hyperomocysteinemia and the development of chronic kidney disease i a general population: The Hisayama study. Am J Kidney Dis 44: 437–445

    PubMed  Google Scholar 

  • Ogburn CE, Carlberg K, Ottinger MA, Holmes DJ, Martin GM and Austad SN (2001) Exceptional cellular resistance to oxidative damage in long-lived birds requires active gene expression. JGerontol 56: B468–B474

    CAS  Google Scholar 

  • Pamplona R and Barja G (2003) Aging rate, free radical production, and constitutive sensitivity to lipid peroxidation: insights from comparative studies. In: Von Zglinicki T (ed) Biology of Aging and Its Modulation Series. Vol.1: Aging at the Molecular Level, pp 47–64. Kluwer, Amsterdam

    Google Scholar 

  • Pamplona R, Prat J, Cadenas S, Rojas C, Pérez-Campo R and López-Torres M et al (1996) Low fatty acid unsaturation protects against lipid peroxidation in liver mitochondria from longevous species: the pigeon and human case. Mech Ageing Dev 86: 53–66

    Article  CAS  PubMed  Google Scholar 

  • Pamplona R, Portero-Otín M, Requena JR, Thorpe SR, Herrero A and Barja G (1999) A low degree of fatty acid unsaturation leadsto lower lipid peroxidation and lipoxidation-derived protein modification in heart mitochondria of the longevous pigeonthan in the short-lived rat. Mech Ageing Dev 106: 283–296

    Article  CAS  PubMed  Google Scholar 

  • Pamplona R, Portero-Otín M, Riba D, Requena JR, Thorpe SR and López-Torres M et al. (2000) Low fatty acid unsaturation: a mechanism for lowered lipoperoxidative modification of tissue proteins in mammalian species with long life span. J Gerontol 55A: B286–B291

    CAS  Google Scholar 

  • Pamplona R, Barja G and Portero-Otín M (2002) Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation. Ann N. Y. Acad Sci 959: 475–490

    CAS  PubMed  Google Scholar 

  • Pamplona R, Dalfo E, Ayala V, Bellmunt MJ, Prat J and Ferrer I etal. (2005) Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. J Biol Chem 280: 21522–21530

    Article  CAS  PubMed  Google Scholar 

  • Pearl R (1928) The rate of living. Alfred A. Knopf, New York

    Google Scholar 

  • Portero-Otin M, Requena JR, Bellmunt MJ, Ayala V and Pamplona R (2004) Protein non-enzymatic modifications and proteasome activity in skeletal muscle from the short-lived rat and long-lived pigeon. Exp Gerontol 39:1527–1535

    CAS  PubMed  Google Scholar 

  • Requena JR, Fu MX, Amed MU, Jenkins AJ, Lyons TJ and Baynes JW et al. (1997) Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoproteins. Biochem J 322: 317– 325

    CAS  PubMed  Google Scholar 

  • Requena JR, Chao CC, Levine RL and Stadtman ER (2001) Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins. Proc Natl Acad Sci USA 98: 69–74

    CAS  PubMed  Google Scholar 

  • Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N and Zimmerman JA (1994) Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J 8: 1302–1307

    CAS  PubMed  Google Scholar 

  • Ruan H, Tang XD, Chen ML, Joiner ML, Sun G and Brot N et al. (2002) High-quality life extension by the enzyme peptide methionine sulfoxide reductase. Proc Natl Acad Sci USA 99: 2748– 2753

    Article  CAS  PubMed  Google Scholar 

  • Ruiz MC, Ayala V, Portero-Otin M, Requena JR, Barja G and Pamplona R (2005) Protein methionine content and MDA-lysine adducts are inversely related to maximum life span in the heart of mammals. Mech Ageing Dev 126: 1106–1114

    Google Scholar 

  • Sanz A, Caro P and Barja G (2004) Protein restriction without strong caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat liver. J Bioenerg Biomembr 36: 545–552

    Article  CAS  PubMed  Google Scholar 

  • Sanz A, Caro P, Ibanez J, Gomez J, Gredilla R and Barja G (2005a) Dietary restriction at old age lowers mitochondrial oxygen radical production and leak at complex I and oxidative DNA damage in rat brain. J Bioenerg Biomembr 37: 83–90

    Article  CAS  PubMed  Google Scholar 

  • Sanz A, Pamplona R and Barja G (2005b) Is mitochondrial free radical theory of aging. intact? Antioxid Redox Signal (in press)

  • Slyshenkov VS, Shevalye AA, Liopo AV and Wojtczak L (2002) Protective role of methionine against free radical damage of ratbrain synaptosomes. Acta Biochim Polonica 49: 907–916

    CAS  Google Scholar 

  • Stadtman ER and Berlett BS (1998) Reactive oxygen-mediated protein oxidation in aging and disease. Drug Metab Rev 30: 225–243

    CAS  PubMed  Google Scholar 

  • Stadtman ER, Van Remmen H, Richardson A, Wehr NB and Levine RL (2005) Methionine oxidation and aging. Biochim Biophys Acta 1703: 135–140

    CAS  PubMed  Google Scholar 

  • St-Pierre J, Buckingham JA, Roebuck SJ and Brand MD (2002) Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277: 44784–44790

    CAS  PubMed  Google Scholar 

  • Takeshige K and Minakami S (1979) NADH- and NADPH-dependent formation of superoxide anions by bovine heart submitochondrial particles and NADH-ubiquinone reductase preparation. Biochem J 180: 129–135

    CAS  PubMed  Google Scholar 

  • Thorpe SR and Baynes JW (2003) Maillard reaction products in tissue proteins: new products. Amino Acids 25: 275–281

    Article  CAS  PubMed  Google Scholar 

  • Turner N, Else PL and Hulbert AJ (2005) An allometric comparison of microsomal membrane lipid composition and sodium pump molecular activity in the brain of mammals and birds. J Exp Biol 208: 371–381

    CAS  PubMed  Google Scholar 

  • Zimmerman JA, Malloy V, Krajcik R and Orentreich N (2003) Nutritional control of aging. Exp Gerontol 38: 47–52

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Basic Medical Sciences, University of Lleida, Lleida, 25198, Spain

    Reinald Pamplona, Manuel Portero-Otín, Victoria Ayala & Ekaterina Vasileva

  2. Department of Animal Physiology-II, Complutense University, Madrid, 28040, Spain

    Alberto Sanz & Gustavo Barja

Authors
  1. Reinald Pamplona
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  2. Manuel Portero-Otín
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  3. Alberto Sanz
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  4. Victoria Ayala
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  5. Ekaterina Vasileva
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  6. Gustavo Barja
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Corresponding authors

Correspondence to Reinald Pamplona or Gustavo Barja.

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Pamplona, R., Portero-Otín, M., Sanz, A. et al. Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate. AGE 27, 267–280 (2005). https://doi.org/10.1007/s11357-005-4562-x

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  • DOI: https://doi.org/10.1007/s11357-005-4562-x

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