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Concept of Aging as a Result of Slow Programmed Poisoning of an Organism with Mitochondrial Reactive Oxygen Species

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Principles of Bioenergetics

Abstract

A small but measurable portion of the molecular oxygen consumed by an organism is converted to superoxide anion (O •−2 ) and H2O2 rather than to H2O. Fe2+ or Cu+ ions can nonenzymatically reduce H2O2 to hydroxyl radical (OH•). At acidic pH, O •−2 is protonated to HO •2 . Moreover, O •−2 can react with NO to form peroxynitrite (NOO−) which, in turn, gives some very aggressive products. These products, together with OH• and HO •2 , are called reactive oxygen species (ROS). O •−2 can be formed as a result of leakage of electrons to O2 from intermediates of the initial and middle steps of mitochondrial respiratory chain. Moreover, there are enzymes reducing O2 to O •−2 or H2O2. Living systems are equipped with a sophisticated antioxidant system. At low concentrations, ROS are used by the cells as short-lived secondary messengers of certain signals. At high concentrations, ROS operate as killers of cells that (a) should be eliminated during ontogenesis, (b) are infected, or (c) are damaged due to cellular senescence. There are some indications that at least in some cases biochemical organismal suicide (phenoptosis) is mediated by mitochondrial ROS (mROS). This may be acute phenoptosis (e.g., septic shock that eliminates from the population the most seriously infected individuals) or slow phenoptosis (programmed aging increasing evolvability of organism). It is suggested that lowering of mROS might be a way to cancel aging of humans since humans are no more interested in their evolution.

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Notes

  1. 1.

    The standard potential of the O •−2 /O2 couple is about −0.3 V. The actual redox potential, being more positive due to [O2] > [O •−2 ], is still in the negative part of the redox potential scale (Skulachev 1994, 2003a; Halliwell and Gutteridge 1999).

  2. 2.

    The described mechanism of mitoptosis is probably not the only way for the cells to get rid of damaged mitochondria. Boris Chernyak, Konstantin Lyamzaev, and colleagues from our group recently discovered that a cell can gather such mitochondria in close proximity to the nucleus, surround them with a membrane, and eject the thus formed mitochondria-containing “mitoptotic body” to the extracellular space (Lyamzaev et al. 2008), see also (Lee et al. 2010; Sterky et al. 2011). This effect was demonstrated in cancer cells of HeLa line growing in the presence of an uncoupler and an inhibitor of the respiratory chain, i.e., agents that stimulate mitochondria to consume ATP instead of producing it. Cancer cells are known to successfully support ATP formation not only by respiration but also by glycolysis, and using this mechanism to destroy damaged mitochondria they can prevent the hydrolysis of the glycolytic ATP by damaged mitochondria. It is suggested that maturation of erythrocytes as well as of crystalline lens cells, accompanied by disappearance of mitochondria, may follow the same mechanism. This would explain the conversion of epithelial cells into the crystalline lens cells even in the absence of autophagy.

  3. 3.

    The ROS-induced opening of the already mentioned permeability transition pore in the inner mitochondrial membrane in one of mechanisms to eliminate the outer mitochondrial membrane as a protein-impermeable barrier. The pore opening results in disappearance of osmotic pressure at the inner membrane since K+ and Cl−, two major ions contributing to osmotic pressure, become permeable for the inner membrane. Now, water is distributed between mitochondrial matrix and cytosol according to the oncotic pressure, i.e., the ratio of concentrations of high molecular mass compounds (first of all, proteins) in the matrix and cytosol. The protein concentration in the matrix is much higher than that in cytosol so water goes to the matrix, which swells. Such swelling means an increase in the matrix volume due to disappearance of invagination of the inner membrane (cristae). The swelling disrupts the outer mitochondrial membrane, which has no invaginations and, hence, has a much smaller area than the inner membrane (Skulachev 1996b).

  4. 4.

    When being completely depleted of ATP, the cell dies in a way different from both apoptosis and necrosis (the so-called energetic catastrophe) (Izyumov et al. 2004; Skulachev 2006).

  5. 5.

    Remarkably, the very fact that the death of semelparous plants is caused by their seeds literally confirms a famous maxim of Weismann (1889) that highly organized living organisms contain “seeds of death”.

  6. 6.

    Such a death seems to be needed for success of sexual reproduction. Bamboo plants reproducing vegetatively are growing so dense that seeds have little chance to find a place to give one more young plant.

  7. 7.

    An elegant experiment was done on wild albatrosses, birds living longer than 50 years. Foraging behavior was studied using satellite tracking. It was found that old males foraged in remote Antarctic waters, whereas young and middle-age males never foraged south of the Polar Front (Lecomte et al. 2010).

  8. 8.

    Reznik was so sure about the lifespan “in hell” being much shorter than “in heaven”, that, when starting his long-term project, he published his prediction of this result (Reznick 1997). In their recent paper, Reznik and colleagues no longer quote their erroneous predictions (Reznick et al. 2004).

  9. 9.

    Compare with the data of Kirkwood and coworkers on the positive correlation between the lifespan of different mammals and the resistance of their fibroblasts to oxidative stress (Kapahi et al. 1999).

  10. 10.

    It is interesting that this feature of aging was noticed by ancient Greeks, who attributed the thought that “aging is the damage to the whole body when its parts remain intact” to the god of healing Asclepius (who turned into Aesculapius in Rome). This does not mean that particular parts of the body do not ultimately decay, but such events seem to occur at a terminal stage which develops long after the aging program had been activated.

References

  • Al-Abdulwahab SS (1999) The effects of aging on muscle strength and functional ability of healthy Saudi Arabian males. Ann Saudi Med 19:211–215

    Google Scholar 

  • Antonenko YN, Avetisyan AV, Bakeeva LE, Chernyak BV, Chertkov VA, Domnina LV, Ivanova OY, Izyumov DS, Khailova LS, Klishin SS, Korshunova GA, Lyamzaev KG, Muntyan MS, Nepryakhina OK, Pashkovskaya AA, Pletjushkina OY, Pustovidko AV, Roginsky VA, Rokitskaya TI, Ruuge EK, Saprunova VB, Severina II, Simonyan RA, Skulachev IV, Skulachev MV, Sumbatyan NV, Sviryaeva IV, Tashlitsky VN, Vassiliev JM, Vyssokikh MY, Yaguzhinsky LS, Zamyatnin AA Jr, Skulachev VP (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies. Biochemistry (Moscow) 73:1273–1287

    Article  Google Scholar 

  • Arantes-Oliveira N, Berman JR, Kenyon C (2003) Healthy animals with extreme longevity. Science 302:611

    Article  Google Scholar 

  • Austad SN (1997) Why we age?. Wiley, New York

    Google Scholar 

  • Barja G (1998) Mitochondrial free radical production and aging in mammals and birds. Ann NY Acad Sci 854:224–238

    Article  ADS  Google Scholar 

  • Barja G, 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

    Google Scholar 

  • Barth C, De Tullio M, Conklin PL (2006) The role of ascorbic acid in the control of flowering time and the onset of senescence. J Exp Bot 57:1657–1665

    Article  Google Scholar 

  • Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–574

    Article  ADS  Google Scholar 

  • Bohle UR, Hilger HH, Martin WF (1996) Island colonization and evolution of the insular woody habit in Echium L (Boraginaceae). Proc Natl Acad Sci U S A 93:11740–11745

    Article  ADS  Google Scholar 

  • Bonduriansky R, Brassil CE (2002) Senescence: rapid and costly ageing in wild male flies. Nature 420:377

    Article  ADS  Google Scholar 

  • Bradley AJ, McDonald IR, Lee AK (1980) Stress and mortality in a small marsupial (Antechinus stuartii, Macleay). Gen Comp Endocrinol 40:188–200

    Article  Google Scholar 

  • Bratton SB, Salvesen GS (2010) Regulation of the Apaf-1-caspase-9 apoptosome. J Cell Sci 123:3209–3214

    Article  Google Scholar 

  • Bredesen DE (2004) The non-existent aging program: how does it work? Aging Cell 3:255–259

    Article  Google Scholar 

  • Brunet-Rossinni AK, Austad SN (2004) Ageing studies on bats: a review. Biogerontology 5:211–222

    Article  Google Scholar 

  • Budrene EO, Berg HC (1991) Complex patterns formed by motile cells of Escherichia coli. Nature 349:630–633

    Article  ADS  Google Scholar 

  • Budrene EO, Berg HC (1995) Dynamics of formation of symmetrical patterns by chemotactic bacteria. Nature 376:49–53

    Article  ADS  Google Scholar 

  • Buffenstein R (2005) The naked mole-rat: a new long-living model for human aging research. J Gerontol A Biol Sci Med Sci 60:1369–1377

    Article  Google Scholar 

  • Burg SP (1968) Ethylene, plant senescence and abscission. Plant Physiol 43:1503–1511

    Article  Google Scholar 

  • Burns RJ, Smith RA, Murphy MP (1995) Synthesis and characterization of thiobutyltriphenylphosphonium bromide, a novel thiol reagent targeted to the mitochondrial matrix. Arch Biochem Biophys 322:60–68

    Article  Google Scholar 

  • Chen XJ, Wang X, Kaufman BA, Butow RA (2005) Aconitase couples metabolic regulation to mitochondrial DNA maintenance. Science 307:714–717

    Article  ADS  Google Scholar 

  • Chen XJ, Wang X, Butow RA (2007) Yeast aconitase binds and provides metabolically coupled protection to mitochondrial DNA. Proc Natl Acad Sci U S A 104:13738–13743

    Article  ADS  Google Scholar 

  • Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR (2010) The BCL-2 family reunion. Mol Cell 37:299–310

    Article  Google Scholar 

  • Christofferson DE, Yuan J (2010) Necroptosis as an alternative form of programmed cell death. Curr Opin Cell Biol 22:263–268

    Article  Google Scholar 

  • Comfort A (1979) The biology of senescence, 3rd edn. Churchill Livingston, Edinburg

    Google Scholar 

  • Darwin C (1871) The Descent of Man. John Murray, London

    Google Scholar 

  • Dilman VM (1971) Age-associated elevation of hypothalamic threshold to feedback control, and its role in development, ageing, and disease. Lancet 1:1211–1219

    Article  Google Scholar 

  • Dilman VM (1978) Ageing, metabolic immunodepression and carcinogenesis. Mech Ageing Dev 8:153–173

    Article  Google Scholar 

  • Dilman VM, Anisimov VN (1979) Hypothalmic mechanisms of ageing and of specific age pathology—I. Sensitivity threshold of hypothalamo-pituitary complex to homeostatic stimuli in the reproductive system. Exp Gerontol 14:161–174

    Article  Google Scholar 

  • Dilman VM (1982) Master biological clock. Znanie (in Russian), Moscow

    Google Scholar 

  • Doughan AK, Dikalov SI (2007) Mitochondrial redox cycling of mitoquinone leads to superoxide production and cellular apoptosis. Antioxid Redox Signal 9:1825–1836

    Article  Google Scholar 

  • Dawkins R (1976) The selfish gene. Oxford University Press, Oxford

    Google Scholar 

  • Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    Article  Google Scholar 

  • Emanuel’ NM (1975) Certain molecular mechanisms and perspectives for prevention of aging. Izv Akad Nauk SSSR 4:785–794 (in Russian)

    Google Scholar 

  • Finch CE (1990) Longevity, senescence, and the genome. University of Chicago Press, Chicago

    Google Scholar 

  • Focher F (2002) “Programmed death” in Schopenhauer’s World? Apoptosis 7:285

    Article  Google Scholar 

  • Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, Michaud M, Zischka H, Castedo M, Kroemer G (2010) Mitochondrial gateways to cancer. Mol Aspects Med 31:1–20

    Article  Google Scholar 

  • Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, Dawson TM, Dawson VL, El-Deiry WS, Fulda S, Gottlieb E, Green DR, Hengartner MO, Kepp O, Knight RA, Kumar S, Lipton SA, Lu X, Madeo F, Malorni W, Mehlen P, Nunez G, Peter ME, Piacentini M, Rubinsztein DC, Shi Y, Simon HU, Vandenabeele P, White E, Yuan J, Zhivotovsky B, Melino G, Kroemer G (2012) Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012. Cell Death Differ 19:107–120

    Article  Google Scholar 

  • Garcia-Cao I, Garcia-Cao M, Martin-Caballero J, Criado LM, Klatt P, Flores JM, Weill JC, Blasco MA, Serrano M (2002) “Super p53” mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 21:6225–6235

    Article  Google Scholar 

  • Gerald D, Berra E, Frapart YM, Chan DA, Giaccia AJ, Mansuy D, Pouyssegur J, Yaniv M, Mechta-Grigoriou F (2004) JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 118:781–794

    Article  Google Scholar 

  • Giles GI (2006) The redox regulation of thiol dependent signaling pathways in cancer. Curr Pharm Des 12:4427–4443

    Article  Google Scholar 

  • Giorgio M, Migliaccio E, Paolucci D (2004) p66shc is a signal transduction red-ox enzyme. In: 13th EBEC Meeting Abstract: 27

    Google Scholar 

  • Goldsmith T (2006) Evolution of aging. Azinet Press, Annapolis

    Google Scholar 

  • Goldstein N (2002) Reactive oxygen species as essential components of ambient air. Biochemistry (Moscow) 67:161–170

    Article  Google Scholar 

  • Green DE (1974) The electromechanochemical model for energy coupling in mitochondria. Biochim Biophys Acta 346:27–78

    Article  Google Scholar 

  • Groover AT (2005) What genes make a tree a tree? Trends Plant Sci 10:210–214

    Article  Google Scholar 

  • Guo Y, Gan S (2011) AtMYB2 regulates whole plant senescence by inhibiting cytokinin-mediated branching at late stages of development in Arabidopsis. Plant Physiol 156:1612–1619

    Article  Google Scholar 

  • Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine, 3rd edn. Oxford University Press, Oxford

    Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300

    Article  Google Scholar 

  • He P, Osaki M, Takebe M, Shinano T, Wasaki J (2005) Endogenous hormones and expression of senescence-related genes in different senescent types of maize. J Exp Bot 56:1117–1128

    Article  Google Scholar 

  • Hekimi S, Guarente L (2003) Genetics and the specificity of the aging process. Science 299:1351–1354

    Article  Google Scholar 

  • Hirota K, Semenza GL (2006) Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol 59:15–26

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P, Le Bouc Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–187

    Article  ADS  Google Scholar 

  • Izyumov DS, Avetisyan AV, Pletjushkina OY, Sakharov DV, Wirtz KW, Chernyak BV, Skulachev VP (2004) “Wages of fear”: transient threefold decrease in intracellular ATP level imposes apoptosis. Biochim Biophys Acta 1658:141–147

    Article  Google Scholar 

  • James AM, Cocheme HM, Smith RA, Murphy MP (2005) Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species. Implications for the use of exogenous ubiquinones as therapies and experimental tools. J Biol Chem 280:21295–21312

    Article  Google Scholar 

  • Jauslin ML, Meier T, Smith RA, Murphy MP (2003) Mitochondria-targeted antioxidants protect Friedreich ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. FASEB J 17:1972–1974

    Google Scholar 

  • Jing HC, Schippers JH, Hille J, Dijkwel PP (2005) Ethylene-induced leaf senescence depends on age-related changes and OLD genes in Arabidopsis. J Exp Bot 56:2915–2923

    Article  Google Scholar 

  • John I, Drake R, Farrell A, Cooper W, Lee P, Horton P, Grierson D (1995) Delayed leaf senescence in ethylene-deficient ACC-oxidase antisense tomato plants: molecular and physiological analysis. Plant J 7:483–490

    Article  Google Scholar 

  • Kapahi P, Boulton ME, Kirkwood TB (1999) Positive correlation between mammalian life span and cellular resistance to stress. Free Radic Biol Med 26:495–500

    Article  Google Scholar 

  • Kashiwagi A, Hanada H, Yabuki M, Kanno T, Ishisaka R, Sasaki J, Inoue M, Utsumi K (1999) Thyroxine enhancement and the role of reactive oxygen species in tadpole tail apoptosis. Free Radic Biol Med 26:1001–1009

    Article  Google Scholar 

  • Kelso GF, Porteous CM, Coulter CV, Hughes G, Porteous WK, Ledgerwood EC, Smith RA, Murphy MP (2001) Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 276:4588–4596

    Article  Google Scholar 

  • Kelso GF, Porteous CM, Hughes G, Ledgerwood EC, Gane AM, Smith RA, Murphy MP (2002) Prevention of mitochondrial oxidative damage using targeted antioxidants. Ann NY Acad Sci 959:263–274

    Article  ADS  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257

    Article  Google Scholar 

  • Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV, Han L, Marino SM, Sun X, Turanov AA, Yang P, Yim SH, Zhao X, Kasaikina MV, Stoletzki N, Peng C, Polak P, Xiong Z, Kiezun A, Zhu Y, Chen Y, Kryukov GV, Zhang Q, Peshkin L, Yang L, Bronson RT, Buffenstein R, Wang B, Han C, Li Q, Chen L, Zhao W, Sunyaev SR, Park TJ, Zhang G, Wang J, Gladyshev VN (2011) Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479:223–227

    Article  ADS  Google Scholar 

  • Kim SC, Crawford DJ, Francisco Ortega J, Santos Guerra A (1996) A common origin for woody Sonchus and five related genera in the Macaronesian islands: molecular evidence for extensive radiation. Proc Natl Acad Sci U S A 93:7743–7748

    Article  ADS  Google Scholar 

  • Kirchner IW, Roy BA (1999) The evolutionary advantages of dying young:epidemiological implications of longevity in metapopulations. Am Nat 145:140–159

    Article  Google Scholar 

  • Kirchner IW, Roy BA (2002) Evolutionary implications of host-pathogen specificity: fitness consequences of pathogen virulence traits. Evol Ecol Res 4:27–40

    Google Scholar 

  • Kirkwood TB, Austad SN (2000) Why do we age? Nature 408:233–238

    Article  ADS  Google Scholar 

  • Kirkwood TB, Cremer T (1982) Cytogerontology since 1881: a reappraisal of August Weismann and a review of modern progress. Hum Genet 60:101–121

    Article  Google Scholar 

  • Kirkwood TB, Melov S (2011) On the programmed/non-programmed nature of ageing within the life history. Curr Biol 21:R701–R707

    Article  Google Scholar 

  • Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132–1136

    Article  Google Scholar 

  • Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484

    Article  ADS  Google Scholar 

  • Labinskyy N, Csiszar A, Orosz Z, Smith K, Rivera A, Buffenstein R, Ungvari Z (2006) Comparison of endothelial function, O •−2 and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice. Am J Physiol Heart Circ Physiol 291:H2698–H2704

    Article  Google Scholar 

  • Lakowski B, Hekimi S (1996) Determination of life-span in Caenorhabditis elegans by four clock genes. Science 272:1010–1013

    Article  ADS  Google Scholar 

  • Lambert AJ, Boysen HM, Buckingham JA, Yang T, Podlutsky A, Austad SN, Kunz TH, Buffenstein R, Brand MD (2007) Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms. Aging Cell 6:607–618

    Article  Google Scholar 

  • Larsson L, Grimby G, Karlsson J (1979) Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 46:451–456

    Google Scholar 

  • Lecomte VJ, Sorci G, Cornet S, Jaeger A, Faivre B, Arnoux E, Gaillard M, Trouvé C, Besson D, Chastel O, Weimerskirch H (2010) Patterns of aging in the long-lived wandering albatross. Proc Natl Acad Sci U S A 107:6370–6375

    Article  ADS  Google Scholar 

  • Lee JY, Nagano Y, Taylor JP, Lim KL, Yao TP (2010) Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. J Cell Biol 189:671–679

    Article  Google Scholar 

  • Lewis K (2000) Programmed death in bacteria. Microbiol Mol Biol Rev 64:503–514

    Article  Google Scholar 

  • Lexell J, Taylor CC, Sjostrom M (1988) What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci 84:275–294

    Article  Google Scholar 

  • Liberman EA, Skulachev VP (1970) Conversion of biomembrane-produced energy into electric form. IV. General discussion. Biochim Biophys Acta 216:30–42

    Article  Google Scholar 

  • Liberman EA, Topaly VP, Tsofina LM, Jasaitis AA, Skulachev VP (1969) Mechanism of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature 222:1076–1078

    Article  ADS  Google Scholar 

  • Libertini G (1988) An adaptive theory of increasing mortality with increasing chronological age in populations in the wild. J Theor Biol 132:145–162

    Article  Google Scholar 

  • Libertini G (2012) Classification of phenoptotic phenomena. Biochemistry (Moscow) 77:707–715

    Google Scholar 

  • Lichtenstein AV (2005) Cancer as a programmed death of an organism. Biochemistry (Moscow) 70:1055–1064

    Article  Google Scholar 

  • Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:147–157

    Article  Google Scholar 

  • Loison A, Festa-Blanchet M, Gaillard J-M, Jorgenson JT, Jullien J-M (1999) Age-specific survival in five populations of ungulates: evidence of senescence. Ecology 80:2539–2554

    Article  Google Scholar 

  • Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342–1346

    Article  Google Scholar 

  • Longo VD, Mitteldorf J, Skulachev VP (2005) Programmed and altruistic ageing. Nat Rev Genet 6(11):866–872

    Article  Google Scholar 

  • Lyamzaev KG, Nepryakhina OK, Saprunova VB, Bakeeva LE, Pletjushkina OY, Chernyak BV, Skulachev VP (2008) Novel mechanism of elimination of malfunctioning mitochondria (mitoptosis): formation of mitoptotic bodies and extrusion of mitochondrial material from the cell. Biochim Biophys Acta 1777:817–825

    Article  Google Scholar 

  • Manskikh VN (2004) Studies in evolutionary oncology. Siberian Medical University Publisher, Tomsk

    Google Scholar 

  • Manskikh VN (2006) Tumor growth as a regulatory mechanism of mutational burden in populations. Biochemistry (Moscow) 71:933–936

    Article  Google Scholar 

  • Medawar PB (1952) An unsolved problem of biology. H. K. Lewis, London

    Google Scholar 

  • Melzer S, Lens F, Gennen J, Vanneste S, Rohde A, Beeckman T (2008) Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana. Nat Genet 40:1489–1492

    Article  Google Scholar 

  • Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L, Pelicci PG (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309–313

    Article  ADS  Google Scholar 

  • Mott JL, Zhang D, Freeman JC, Mikolajczak P, Chang SW, Zassenhaus HP (2004) Cardiac disease due to random mitochondrial DNA mutations is prevented by cyclosporin A. Biochem Biophys Res Commun 319:1210–1215

    Article  Google Scholar 

  • Murphy MP, Smith RA (2007) Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol 47:629–656

    Article  Google Scholar 

  • Naik E, Dixit VM (2011) Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med 208:417–420

    Article  Google Scholar 

  • Napoli C, Martin-Padura I, de Nigris F, Giorgio M, Mansueto G, Somma P, Condorelli M, Sica G, De Rosa G, Pelicci P (2003) Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci U S A 100:2112–2116

    Article  ADS  Google Scholar 

  • Narendra DP, Youle RJ (2011) Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid Redox Signal 14:1929–1938

    Article  Google Scholar 

  • Navabpour S, Morris K, Allen R, Harrison E, A-H-Mackerness S, Buchanan-Wollaston V (2003) Expression of senescence-enhanced genes in response to oxidative stress. J Exp Bot 54:2285–2292

    Article  Google Scholar 

  • Neljubow D (1901) Über die Nutation der Stengel von Pisum sativum und einiger anderen Pflanzen. Bot Cetrabl Beihefte 10:128–139

    Google Scholar 

  • Nesis KN (1997) Cruel love among the squids. In: Byalko AV (ed) Russian science: withstand and revive. Nauka-Physmatlit, Moscow, pp 358–365 (in Russian)

    Google Scholar 

  • Nooden LD, Murray BJ (1982) Transmission of the monocarpic senescence signal via the xylem in soybean. Plant Physiol 69:754–756

    Article  Google Scholar 

  • O’Malley Y, Fink BD, Ross NC, Prisinzano TE, Sivitz WI (2006) Reactive oxygen and targeted antioxidant administration in endothelial cell mitochondria. J Biol Chem 281:39766–39775

    Article  Google Scholar 

  • Orrenius S, Nicotera P, Zhivotovsky B (2011) Cell death mechanisms and their implications in toxicology. Toxicol Sci 119:3–19

    Article  Google Scholar 

  • Osiewacz HD (2003) Aging and mitochondrial dysfunction in the filamentous fungus Podospora anserina. In: Nyström T, Osiewacz HD (eds) Topics in current genetics, vol 3. Springer, Berlin, pp 17–38

    Google Scholar 

  • Park TJ, Lu Y, Juttner R, Smith ES, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP, Lewin GR (2008) Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber). PLoS Biol 6:e13

    Article  Google Scholar 

  • Pletjushkina OY, Fetisova EK, Lyamzaev KG, Ivanova OY, Domnina LV, Vyssokikh MY, Pustovidko AV, Vasiliev JM, Murphy MP, Chernyak BV, Skulachev VP (2005) Long-distance apoptotic killing of cells is mediated by hydrogen peroxide in a mitochondrial ROS-dependent fashion. Cell Death Differ 12:1442–1444

    Article  Google Scholar 

  • Powers SK, Talbert EE, Adhihetty PJ (2011) Reactive oxygen and nitrogen species as intracellular signals in skeletal muscle. J Physiol 589:2129–2138

    Article  Google Scholar 

  • Pozniakovsky AI, Knorre DA, Markova OV, Hyman AA, Skulachev VP, Severin FF (2005) Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. J Cell Biol 168:257–269

    Article  Google Scholar 

  • Price AM, Aros Orellana DF, Salleh FM, Stevens R, Acock R, Buchanan-Wollaston V, Stead AD, Rogers HJ (2008) A comparison of leaf and petal senescence in wallflower reveals common and distinct patterns of gene expression and physiology. Plant Physiol 147:1898–1912

    Article  Google Scholar 

  • Reznick DN (1997) Life history evolution in guppies (Poecilia reticulata): guppies as a model for studying the evolutionary biology of aging. Exp Gerontol 32:245–258

    Article  Google Scholar 

  • Reznick DN, Bryant MJ, Roff D, Ghalambor CK, Ghalambor DE (2004) Effect of extrinsic mortality on the evolution of senescence in guppies. Nature 431:1095–1099

    Article  ADS  Google Scholar 

  • Rigoulet M, Yoboue ED, Devin A (2011) Mitochondrial ROS generation and its regulation: mechanisms involved in H2O2 signaling. Antioxid Redox Signal 14:459–468

    Article  Google Scholar 

  • Ross JJ, Weston DE, Davidson SE, Reid JB (2011) Plant hormone interactions: how complex are they? Physiol Plant 141:299–309

    Article  Google Scholar 

  • Saule P, Trauet J, Dutriez V, Lekeux V, Dessaint JP, Labalette M (2006) Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment. Mech Ageing Dev 127:274–281

    Article  Google Scholar 

  • Schopenhauer A (1969) The world as will and representation. Dover Publications, New York

    Google Scholar 

  • Saretzki G, Murphy MP, von Zglinicki T (2003) MitoQ counteracts telomere shortening and elongates lifespan of fibroblasts under mild oxidative stress. Aging Cell 2:141–143

    Article  Google Scholar 

  • Scrable H, Burns-Cusato M, Medrano S (2009) Anxiety and the aging brain: stressed out over p53? Biochim Biophys Acta 1790:1587–1591

    Article  Google Scholar 

  • Severin FF, Skulachev VP (2011) Programmed cell death as a target to interrupt the aging program. Adv Gerontol 1:16–27

    Article  Google Scholar 

  • Severin SE, Skulachev VP, Yaguzhinskii LS (1970) Possible role of carnitine in the transport of fatty acids through the mitochondrial membrane. Biokhimia 35:1250–1253 (in Russian)

    Google Scholar 

  • Shan X, Yan J, Xie D (2012) Comparison of phytohormone signaling mechanisms. Curr Opin Plant Biol 15:84–91

    Article  Google Scholar 

  • Shchepina LA, Pletjushkina OY, Avetisyan AV, Bakeeva LE, Fetisova EK, Izyumov DS, Saprunova VB, Vyssokikh MY, Chernyak BV, Skulachev VP (2002) Oligomycin, inhibitor of the Fo part of H+-ATP-synthase, suppresses the TNF-induced apoptosis. Oncogene 21:8149–8157

    Article  Google Scholar 

  • Skulachev VP (1988) Membrane bioenergetics. Springer, Berlin

    Book  Google Scholar 

  • Skulachev VP (1994) Lowering of intracellular O2 concentration as a special function of respiratory systems of cells. Biochemistry (Moscow) 59:1433–1434 (in Russian)

    Google Scholar 

  • Skulachev VP (1996a) Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants. Q Rev Biophys 29:169–202

    Article  Google Scholar 

  • Skulachev VP (1996b) Why are mitochondria involved in apoptosis? Permeability transition pores and apoptosis as selective mechanisms to eliminate superoxide-producing mitochondria and cell. FEBS Lett 397:7–10

    Article  Google Scholar 

  • Skulachev VP (1997) Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann’s hypothesis. Biochemistry (Moscow) 62:1191–1195

    Google Scholar 

  • Skulachev VP (1998) Possible role of reactive oxygen species in antiviral defense. Biochemistry (Moscow) 63:1438–1440

    Google Scholar 

  • Skulachev VP (1999a) Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms. Mol Aspects Med 20:139–184

    Article  Google Scholar 

  • Skulachev VP (1999b) Phenoptosis: programmed death of an organism. Biochemistry (Moscow) 64:1418–1426

    Google Scholar 

  • Skulachev VP (2000) Mitochondria in the programmed death phenomena; a principle of biology: “It is better to die than to be wrong”. IUBMB Life 49:365–373

    Article  Google Scholar 

  • Skulachev VP (2002) Programmed death phenomena: from organelle to organism. Ann NY Acad Sci 959:214–237

    Article  ADS  Google Scholar 

  • Skulachev VP (2003a) Aging and programmed death phenomena. In: Nystrom T, Osiewacz HD (eds) Topics in current cenetics. Model systems in ageing, vol 3. Springer, Berlin, pp 191–238

    Google Scholar 

  • Skulachev VP (2003b) A Nobel Prize for studies on programmed cell death. Biochemistry (Moscow) 68:290–291 (in Russian)

    Google Scholar 

  • Skulachev VP (2005) Aging as an atavistic program which might be switched off? Vestnik Rus Acad Sci 75:831–843 (in Russian)

    Google Scholar 

  • Skulachev VP (2006) Bioenergetic aspects of apoptosis, necrosis and mitoptosis. Apoptosis 11:473–485

    Article  Google Scholar 

  • Skulachev VP (2007) A biochemical approach to the problem of aging: “megaproject” on membrane-penetrating ions. The first results and prospects. Biochemistry (Moscow) 72:1385–1396

    Article  Google Scholar 

  • Skulachev VP (2009) How to cancel the aging program of organism? Rus Khim Zh 53(3):125–140 (in Russian)

    Google Scholar 

  • Skulachev VP (2011) Aging as a particular case of phenoptosis, the programmed death of an organism (a response to Kirkwood and Melov “On the programmed/non-programmed nature of ageing within the life history”). Aging 3:1120–1123

    Google Scholar 

  • Skulachev VP (2012) What is "phenoptosis" and how to fight it? Biochemistry (Moscow) 77:689–706

    Google Scholar 

  • Skulachev VP, Longo VD (2005) Aging as a mitochondria-mediated atavistic program: can aging be switched off? Ann NY Acad Sci 1057:145–164

    Article  ADS  Google Scholar 

  • Skulachev VP, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, Filenko OF, Kalinina NI, Kapelko VI, Kolosova NG, Kopnin BP, Korshunova GA, Lichinitser MR, Obukhova LA, Pasyukova EG, Pisarenko OI, Roginsky VA, Ruuge EK, Senin II, Severina II, Skulachev MV, Spivak IM, Tashlitsky VN, Tkachuk VA, Vyssokikh MY, Yaguzhinsky LS, Zorov DB (2009) An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta 1787:437–461

    Article  Google Scholar 

  • Smith RA, Porteous CM, Coulter CV, Murphy MP (1999) Selective targeting of an antioxidant to mitochondria. Eur J Biochem 263:709–716

    Article  Google Scholar 

  • Sommer SS (1994) Does cancer kill the individual and save the species? Hum Mutat 3:166–169

    Article  Google Scholar 

  • Sterky FH, Lee S, Wibom R, Olson L, Larsson NG (2011) Impaired mitochondrial transport and Parkin-independent degeneration of respiratory chain-deficient dopamine neurons in vivo. Proc Natl Acad Sci U S A 108:12937–12942

    Article  ADS  Google Scholar 

  • Susin SA, Zamzami N, Castedo M, Hirsch T, Marchetti P, Macho A, Daugas E, Geuskens M, Kroemer G (1996) Bcl-2 inhibits the mitochondrial release of an apoptogenic protease. J Exp Med 184:1331–1341

    Article  Google Scholar 

  • Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446

    Article  ADS  Google Scholar 

  • Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci U S A 45:30–45

    Article  ADS  MATH  Google Scholar 

  • Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632

    Article  Google Scholar 

  • Terzibasi E, Valenzano DR, Cellerino A (2007) The short-lived fish Nothobranchius furzeri as a new model system for aging studies. Exp Gerontol 42:81–89

    Article  Google Scholar 

  • Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:417–423

    Article  ADS  Google Scholar 

  • Trinei M, Giorgio M, Cicalese A, Barozzi S, Ventura A, Migliaccio E, Milia E, Padura IM, Raker VA, Maccarana M, Petronilli V, Minucci S, Bernardi P, Lanfrancone L, Pelicci PG (2002) A p53–p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21:3872–3878

    Article  Google Scholar 

  • Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Hee Park S, Thompson T, Karsenty G, Bradley A, Donehower LA (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415:45–53

    Article  ADS  Google Scholar 

  • Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010) Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 11:700–714

    Article  Google Scholar 

  • Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43–53

    Article  Google Scholar 

  • Weismann A (1889) Essays upon heredity and kindred biological problems. Claderon Press, Oxford

    Google Scholar 

  • Wi SJ, Jang SJ, Park KY (2010) Inhibition of biphasic ethylene production enhances tolerance to abiotic stress by reducing the accumulation of reactive oxygen species in Nicitiana tabacum. Mol Cells 30:37–49

    Article  Google Scholar 

  • Wodinsky J (1977) Hormonal inhibition of feeding and death in octopus: control by optic gland secretion. Science 198:948–951

    Article  ADS  Google Scholar 

  • Yuan J, Kroemer G (2010) Alternative cell death mechanisms in development and beyond. Genes Dev 24:2592–2602

    Article  Google Scholar 

  • Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science 275:1129–1132

    Article  Google Scholar 

  • Zorov DB, Kinnally KW, Tedeschi H (1992) Voltage activation of heart inner mitochondrial membrane channels. J Bioenerg Biomembr 24:119–124

    Article  Google Scholar 

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  1. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Bldg. 44, Moscow, Russia, 119991

    Vladimir P. Skulachev & Alexander V. Bogachev

  2. Faculty of Biology, Moscow State University, Leninskie Gory 1-12, Moscow, Russia, 119991

    Felix O. Kasparinsky

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  1. Vladimir P. Skulachev
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Skulachev, V.P., Bogachev, A.V., Kasparinsky, F.O. (2013). Concept of Aging as a Result of Slow Programmed Poisoning of an Organism with Mitochondrial Reactive Oxygen Species. In: Principles of Bioenergetics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33430-6_15

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