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Part of the book series: SpringerBriefs in Molecular Medicine ((BRIEFSMOME))

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Abstract

The more one learns about single processes and genes known to be involved in aging, the more it becomes evident that these are connected and there is no unifying theory of aging. The individual theories put individual factors and processes in focus and for each theory there are direct links to life span or to age-related disorders. In the following chapter, the key theories of aging focusing on telomeres, DNA damage, oxidative stress as well as possible roles of nutrition, the interplay between genes and environment (epigenetics) and cellular protein homeostasis are presented. In animal models the life span can be altered by targeting specific genes, proteins and signalling pathways. After reviewing all these different mechanisms and factors obviously involved in the aging process of cells and organisms it becomes clear that aging is a multifactorial process where various intimate mutual interactions can be identified. Consequently, at the end of this chapter the idea of a molecular aging matrix composed of the major players affecting and triggering the aging process is developed.

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References

  • Adwan L, Zawia NH (2013) Epigenetics: a novel therapeutic approach for the treatment of Alzheimer’s disease. Pharmacol Ther 139(1):41–50

    Google Scholar 

  • Alberts B, Johnson A, Walter P, Lewis J, Raff M, Roberts K (2007) Molecular biology of the cell, 5th revised edn. Taylor & Francis, New York

    Google Scholar 

  • Alegría-Torres JA, Baccarelli A, Bollati V (2011) Epigenetics and lifestyle. Epigenomics 3(3):267–277

    PubMed Central  PubMed  Google Scholar 

  • Alexander P (1967) The role of DNA lesions in processes leading to aging in mice. Symp Soc Exp Biol 21:29–50

    CAS  PubMed  Google Scholar 

  • Amm I, Sommer T, Wolf DH (2013) Protein quality control and elimination of protein waste: the role of the ubiquitin-proteasome system. Biochim Biophys Acta [Epub ahead of print]

    Google Scholar 

  • Anselmi B, Conconi M, Veyrat-Durebex C, Turlin E, Biville F, Alliot J, Friguet B (1998) Dietary self-selection can compensate an age-related decrease of rat liver 20 S proteasome activity observed with standard diet. J Gerontol A Biol Sci Med Sci 53(3):B173–B179

    CAS  PubMed  Google Scholar 

  • Atzmon G, Cho M, Cawthon RM, Budagov T, Katz M, Yang X, Siegel G, Bergman A, Huffman DM, Schechter CB, Wright WE, Shay JW, Barzilai N, Govindaraju DR, Suh Y (2010) Evolution in health and medicine Sackler colloquium: genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A 107(Suppl 1):1710–1717

    CAS  PubMed Central  PubMed  Google Scholar 

  • Austad SN (2010) Methusaleh’s Zoo: how nature provides us with clues for extending human health span. J Comp Pathol 142(Suppl 1):S10–S21

    PubMed Central  PubMed  Google Scholar 

  • Bae YS, Oh H, Rhee SG, Yoo YD (2011) Regulation of reactive oxygen species generation in cell signaling. Mol Cells 32(6):491–509

    CAS  PubMed  Google Scholar 

  • Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495

    CAS  PubMed  Google Scholar 

  • Barneda-Zahonero B, Parra M (2012) Histone deacetylases and cancer. Mol Oncol 6(6):579–589

    CAS  PubMed  Google Scholar 

  • Bartke A (2011) Single-gene mutations and healthy ageing in mammals. Philos Trans R Soc Lond B Biol Sci 366(1561):28–34

    CAS  PubMed  Google Scholar 

  • Bártová E, Krejcí J, Harnicarová A, Galiová G, Kozubek S (2008) Histone modifications and nuclear architecture: a review. J Histochem Cytochem 56(8):711–721

    PubMed  Google Scholar 

  • Beauharnois JM, Bolívar BE, Welch JT (2013) Sirtuin 6: a review of biological effects and potential therapeutic properties. Mol Biosyst 9(7):1789–1806

    CAS  PubMed  Google Scholar 

  • Behl C, Davis JB, Lesley R, Schubert D (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77(6):817–827

    CAS  PubMed  Google Scholar 

  • Behl C, Moosmann B (2002) Oxidative nerve cell death in Alzheimer’s disease and stroke: antioxidants as neuroprotective compounds. Biol Chem 383(3–4):521–536

    CAS  PubMed  Google Scholar 

  • Behl C (2012) Brain aging and late-onset Alzheimer’s disease: many open questions. Int Psychogeriatr 24(Suppl 1):S3–S9

    PubMed  Google Scholar 

  • Behl C, Moosmann B (2008) Molekulare Mechanismen des Alterns. Über das Altern der Zellen und den Einfluss von oxidativem Stress auf den Alternsprozess. In: Staudinger UM, Häfner H (eds) Was ist Alter(n)? Neue Antworten auf eine scheinbar einfache Frage, pp 9–32. Spinger, Berlin [Schriften der Mathematisch-naturwissenschaftlichen Klasse der Heidelberger Akademie der Wissenschaften, Nr. 18, 2008]

    Google Scholar 

  • Ben-Avraham D, Muzumdar RH, Atzmon G (2012) Epigenetic genome-wide association methylation in aging and longevity. Epigenomics 4(5):503–509

    CAS  PubMed  Google Scholar 

  • Bender A, Hajieva P, Moosmann B (2008) Adaptive antioxidant methionine accumulation in respiratory chain complexes explains the use of a deviant genetic code in mitochondria. Proc Natl Acad Sci U S A 105(43):16496–16501

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A (2009) An operational definition of epigenetics. Genes Dev 23(7):781–783

    CAS  PubMed  Google Scholar 

  • Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekström TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP (2008) Intra-individual change over time in DNA methylation with familial clustering. JAMA 299(24):2877–2883

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blüher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299(5606):572–574

    PubMed  Google Scholar 

  • Bourzac K (2012) Interventions: live long and prosper. Nature 492(7427):S18–S20

    CAS  PubMed  Google Scholar 

  • Branzei D, Foiani M (2008) Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9(4):297–308

    CAS  PubMed  Google Scholar 

  • Brown MK, Naidoo N (2012) The endoplasmic reticulum stress response in aging and age-related diseases. Front Physiol 3:263

    PubMed Central  PubMed  Google Scholar 

  • Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384(6604):33

    CAS  PubMed  Google Scholar 

  • Brown-Borg HM, Bartke A (2012) GH and IGF1: roles in energy metabolism of long-living GH mutant mice. J Gerontol A Biol Sci Med Sci 67(6):652–660

    PubMed  Google Scholar 

  • Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125(3):443–451

    CAS  PubMed  Google Scholar 

  • Burgess RJ, Zhang Z (2010) Histones, histone chaperones and nucleosome assembly. Protein Cell 1(7):607–612

    CAS  PubMed  Google Scholar 

  • Burtner CR, Kennedy BK (2010) Progeria syndromes and ageing: what is the connection? Nat Rev Mol Cell Biol 11(8):567–578

    CAS  PubMed  Google Scholar 

  • Busque L, Mio R, Mattioli J, Brais E, Blais N, Lalonde Y, Maragh M, Gilliland DG (1996) Nonrandom X-inactivation patterns in normal females: lyonization ratios vary with age. Blood 88(1):59–65

    CAS  PubMed  Google Scholar 

  • Carafa V, Nebbioso A, Altucci L (2012) Sirtuins and disease: the road ahead. Front Pharmacol 3:4

    CAS  PubMed Central  PubMed  Google Scholar 

  • Casorelli I, Bossa C, Bignami M (2012) DNA damage and repair in human cancer: molecular mechanisms and contribution to therapy-related leukemias. Int J Environ Res Public Health 9(8):2636–2657

    CAS  PubMed  Google Scholar 

  • Cech TR (2004) Beginning to understand the end of the chromosome. Cell 116(2):273–279

    CAS  PubMed  Google Scholar 

  • Chavez E, Vulto I, Lansdorp PM (2009) Telomere length in Hutchinson-Gilford progeria syndrome. Mech Ageing Dev 130(6):377–383

    PubMed  Google Scholar 

  • Chen Y, Klionsky DJ (2011) The regulation of autophagy—unanswered questions. J Cell Sci 124(Pt 2):161–170

    CAS  PubMed  Google Scholar 

  • Chevanne M, Calia C, Zampieri M, Cecchinelli B, Caldini R, Monti D, Bucci L, Franceschi C, Caiafa P (2007) Oxidative DNA damage repair and parp 1 and parp 2 expression in Epstein-Barr virus-immortalized B lymphocyte cells from young subjects, old subjects, and centenarians. Rejuvenation Res 10(2):191–204

    CAS  PubMed  Google Scholar 

  • Chouliaras L, van den Hove DL, Kenis G, Keitel S, Hof PR, van Os J, Steinbusch HW, Schmitz C, Rutten BP (2012) Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction. Neurobiol Aging 33(8):1672–1681

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292(5514):104–106

    CAS  PubMed  Google Scholar 

  • Cleaver JE, Lam ET, Revet I (2009) Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat Rev Genet 10(11):756–768

    CAS  PubMed  Google Scholar 

  • Clement AB, Gamerdinger M, Tamboli IY, Lütjohann D, Walter J, Greeve I, Gimpl G, Behl C (2009) Adaptation of neuronal cells to chronic oxidative stress is associated with altered cholesterol and sphingolipid homeostasis and lysosomal function. J Neurochem 111(3):669–682

    CAS  PubMed  Google Scholar 

  • Clement AB, Gimpl G, Behl C (2010) Oxidative stress resistance in hippocampal cells is associated with altered membrane fluidity and enhanced nonamyloidogenic cleavage of endogenous amyloid precursor protein. Free Radic Biol Med 48(9):1236–1241

    CAS  PubMed  Google Scholar 

  • Cline SD (2012) Mitochondrial DNA damage and its consequences for mitochondrial gene expression. Biochim Biophys Acta 1819(9–10):979–991

    CAS  PubMed Central  PubMed  Google Scholar 

  • Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204

    CAS  PubMed Central  PubMed  Google Scholar 

  • Corey DR (2009) Telomeres and telomerase: from discovery to clinical trials. Chem Biol 16(12):1219–1223

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cornaro L (2005) English translation by Butler WF (1903) The art of living long. Springer, New York

    Google Scholar 

  • Couzin-Frankel J (2011) Genetics. Aging genes: the sirtuin story unravels. Science 334(6060):1194–1198

    Google Scholar 

  • Cuervo AM, Dice JF (2000) Age-related decline in chaperone-mediated autophagy. J Biol Chem 275(40):31505–31513

    CAS  PubMed  Google Scholar 

  • Culotta E, Koshland DE Jr (1992) NO news is good news. Science 258(5090):1862–1865

    CAS  PubMed  Google Scholar 

  • Curtin NJ (2012) DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 12(12):801–817

    CAS  PubMed  Google Scholar 

  • D’Aquila P, Rose G, Bellizzi D, Passarino G (2013) Epigenetics and aging. Maturitas 74(2):130–136

    PubMed  Google Scholar 

  • Dasuri K, Zhang L, Keller JN (2013) Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic Biol Med 62:170–185

    CAS  PubMed  Google Scholar 

  • David DC, Ollikainen N, Trinidad JC, Cary MP, Burlingame AL, Kenyon C (2010) Widespread protein aggregation as an inherent part of aging in C. elegans. PLoS Biol 8:e1000450

    Google Scholar 

  • David DC (2012) Aging and the aggregating proteome. Front Genet 3:247

    PubMed Central  PubMed  Google Scholar 

  • Decker ML, Chavez E, Vulto I, Lansdorp PM (2009) Telomere length in Hutchinson-Gilford progeria syndrome. Mech Ageing Dev 130(6):377–383

    Google Scholar 

  • Dhurandhar EJ, Allison DB, van Groen T, Kadish I (2013) Hunger in the absence of caloric restriction improves cognition and attenuates Alzheimer’s disease pathology in a mouse model. PLoS One 8(4):e60437

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dikic I, Johansen T, Kirkin V (2010) Selective autophagy in cancer development and therapy. Cancer Res 70(9):3431–3434

    CAS  PubMed  Google Scholar 

  • Dobashi Y, Watanabe Y, Miwa C, Suzuki S, Koyama S (2011) Mammalian target of rapamycin: a central node of complex signaling cascades. Int J Clin Exp Pathol 4(5):476–495

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dong S, Duan Y, Hu Y, Zhao Z (2012) Advances in the pathogenesis of Alzheimer’s disease: a re-evaluation of amyloid cascade hypothesis. Transl Neurodegener 1(1):18

    CAS  PubMed Central  PubMed  Google Scholar 

  • Donmez G, Wang D, Cohen DE, Guarente L (2010) SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell 142(2):320–332 (Erratum in: Cell 142(3):494–495)

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dorman JB, Albinder B, Shroyer T, Kenyon C (1995) The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics 141(4):1399–1406

    CAS  PubMed  Google Scholar 

  • Dunlop RA, Brunk UT, Rodgers KJ (2009) Oxidized proteins: mechanisms of removal and consequences of accumulation. IUBMB Life 61(5):522–527

    CAS  PubMed  Google Scholar 

  • De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492

    PubMed  Google Scholar 

  • Ewbank JJ (2006) Signaling in the immune response (23 Jan 2006). In: WormBook (ed) The C. elegans research community, WormBook. doi:10.1895/wormbook.1.83.1, http://www.wormbook.org

  • Fontana L, Partridge L, Longo VD (2010) Extending healthy life span-from yeast to humans. Science 328(5976):321–326

    CAS  PubMed Central  PubMed  Google Scholar 

  • Foster DA, Yellen P, Xu L, Saqcena M (2010) Regulation of G1 cell cycle progression: distinguishing the restriction point from a nutrient-sensing cell growth checkpoint(s). Genes Cancer 1(11):1124–1131

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23(8):413–418

    Google Scholar 

  • Fredrickson EK, Gardner RG (2012) Selective destruction of abnormal proteins by ubiquitin-mediated protein quality control degradation. Semin Cell Dev Biol 23(5):530–537

    CAS  PubMed Central  PubMed  Google Scholar 

  • Freeman JA, Espinosa JM (2013) The impact of post-transcriptional regulation in the p53 network. Brief Funct Genomics 12(1):46–57

    CAS  PubMed  Google Scholar 

  • Freitas AA, de Magalhães JP (2011) A review and appraisal of the DNA damage theory of ageing. Mutat Res 728(1–2):12–22

    CAS  PubMed  Google Scholar 

  • Friedman DB, Johnson TE (1988) A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118(1):75–86

    CAS  PubMed  Google Scholar 

  • Galjaard S, Devlieger R, Van Assche FA (2013) Fetal growth and developmental programming. J Perinat Med 41(1):101–105

    PubMed  Google Scholar 

  • Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C (2009) Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. EMBO J 28(7):889–901

    CAS  PubMed  Google Scholar 

  • Gamerdinger M, Carra S, Behl C (2011b) Emerging roles of molecular chaperones and co-chaperones in selective autophagy: focus on BAG proteins. J Mol Med (Berl) 89(12):1175–1182

    CAS  Google Scholar 

  • Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C (2011a) BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep 12(2):149–56

    Google Scholar 

  • Gensler HL, Bernstein H (1981) DNA damage as the primary cause of aging. Q Rev Biol 56(3):279–303

    CAS  PubMed  Google Scholar 

  • Germann MW, Johnson CN, Spring AM (2012) Recognition of damaged DNA: structure and dynamic markers. Med Res Rev 32(3):659–683

    CAS  PubMed  Google Scholar 

  • Gkogkolou P, Böhm M (2012) Advanced glycation end products: key players in skin aging? Dermatoendocrinol 4(3):259–270

    CAS  PubMed Central  PubMed  Google Scholar 

  • González-Suárez E, Geserick C, Flores JM, Blasco MA (2005) Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice. Oncogene 24(13):2256–2270

    PubMed  Google Scholar 

  • Gonzalo S (2010) Epigenetic alterations in aging. J Appl Physiol 109(2):586–597

    CAS  PubMed  Google Scholar 

  • Gredilla R, Garm C, Stevnsner T (2012) Nuclear and mitochondrial DNA repair in selected eukaryotic aging model systems. Oxid Med Cell Longev 2012:282438

    PubMed Central  PubMed  Google Scholar 

  • Greer EL, Maures TJ, Hauswirth AG, Green EM, Leeman DS, Maro GS, Han S, Banko MR, Gozani O, Brunet A (2010) Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature 466(7304):383–387

    CAS  PubMed Central  PubMed  Google Scholar 

  • Greeve I, Hermans-Borgmeyer I, Brellinger C, Kasper D, Gomez-Isla T, Behl C, Levkau B, Nitsch RM (2000) The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer’s disease-associated neurodegeneration and oxidative stress. J Neurosci 20(19):7345–7352

    CAS  PubMed  Google Scholar 

  • Greider CW, Blackburn EH (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43(2 Pt 1):405–413

    CAS  PubMed  Google Scholar 

  • Grillari J, Grillari-Voglauer R (2010) Novel modulators of senescence, aging, and longevity: small non-coding RNAs enter the stage. Exp Gerontol 45(4):302–311

    CAS  PubMed  Google Scholar 

  • Guarente L (2011) Franklin H. Epstein lecture: sirtuins, aging, and medicine. N Engl J Med 364(23):2235–2244

    CAS  PubMed  Google Scholar 

  • Guarente L (2013) Calorie restriction and sirtuins revisited. Genes Dev 27(19):2072–2085

    CAS  PubMed  Google Scholar 

  • Gupta J, Tikoo K (2012) Involvement of insulin-induced reversible chromatin remodeling in altering the expression of oxidative stress-responsive genes under hyperglycemia in 3T3-L1 preadipocytes. Gene 504(2):181–191

    Google Scholar 

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

    Google Scholar 

  • Hammond SM (2005) Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Lett 579(26):5822–5829

    CAS  PubMed  Google Scholar 

  • Harley CB, Sherwood SW (1997) Telomerase, checkpoints and cancer. Cancer Surv 29:263–284

    CAS  PubMed  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300

    CAS  PubMed  Google Scholar 

  • Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147

    CAS  PubMed  Google Scholar 

  • Harman D (2009) About “origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009”. Biogerontology 10(6):783

    PubMed  Google Scholar 

  • Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hartl FU, Hayer-Hartl M (2002) Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852–1858

    CAS  PubMed  Google Scholar 

  • He L, He X, Lowe SW, Hannon GJ (2007) MicroRNAs join the p53 network—another piece in the tumour-suppression puzzle. Nat Rev Cancer 7(11):819–822

    CAS  PubMed  Google Scholar 

  • He XJ, Chen T, Zhu JK (2011) Regulation and function of DNA methylation in plants and animals. Cell Res 21(3):442–465

    CAS  PubMed  Google Scholar 

  • Hecht SS (2012) Lung carcinogenesis by tobacco smoke. Int J Cancer 131(12):2724–2732

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heilbronn LK, de Jonge L, Frisard MI, DeLany JP, Larson-Meyer DE, Rood J, Nguyen T, Martin CK, Volaufova J, Most MM, Greenway FL, Smith SR, Deutsch WA, Williamson DA, Ravussin E, Pennington CALERIE Team (2006) Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA 295(13):1539–48 (Erratum in: JAMA 295(21):2482)

    Google Scholar 

  • Heydari AR, You S, Takahashi R, Gutsmann-Conrad A, Sarge KD, Richardson A (2000) Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes. Exp Cell Res 256:83–93

    CAS  PubMed  Google Scholar 

  • Hochfeld WE, Lee S, Rubinsztein DC (2013) Therapeutic induction of autophagy to modulate neurodegenerative disease progression. Acta Pharmacol Sin 34(5):600–604

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411(6835):366–374

    CAS  PubMed  Google Scholar 

  • Holsboer F (2007) Altersbedingte Erkrankungen: Das Wechselspiel von Veranlagung und Lebensweise. In: Gruss P (ed) Die Zukunft des Alterns, pp 163–191. C.H. Beck, München

    Google Scholar 

  • Holzenberger M, Dupont J, Ducos B, Leneuve P, Géloën A, Even PC, Cervera P, Le Bouc Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421(6919):182–187

    CAS  PubMed  Google Scholar 

  • Horcajada MN, Offord E (2012) Naturally plant-derived compounds: role in bone anabolism. Curr Mol Pharmacol 5(2):205–218

    CAS  PubMed  Google Scholar 

  • Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425(6954):191–196

    CAS  PubMed  Google Scholar 

  • Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–1145

    CAS  PubMed  Google Scholar 

  • Humphreys V, Martin RM, Ratcliffe B, Duthie S, Wood S, Gunnell D, Collins AR (2007) Age-related increases in DNA repair and antioxidant protection: a comparison of the Boyd Orr Cohort of elderly subjects with a younger population sample. Age Ageing 36(5):521–526

    PubMed  Google Scholar 

  • Ibáñez-Ventoso C, Driscoll M (2009) MicroRNAs in C. elegans aging: molecular insurance for robustness? Curr Genomics 10(3):144–153

    PubMed  Google Scholar 

  • Jeck WR, Siebold AP, Sharpless NE (2012) Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell 11(5):727–731

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jena NR (2012) DNA damage by reactive species: mechanisms, mutation and repair. J Biosci 37(3):503–517

    CAS  PubMed  Google Scholar 

  • Jeppesen DK, Bohr VA, Stevnsner T (2011) DNA repair deficiency in neurodegeneration. Prog Neurobiol 94(2):166–200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jones QR, Warford J, Rupasinghe HP, Robertson GS (2012) Target-based selection of flavonoids for neurodegenerative disorders. Trends Pharmacol Sci 33(11):602–610

    CAS  PubMed  Google Scholar 

  • Jung T, Bader N, Grune T (2007) Lipofuscin: formation, distribution, and metabolic consequences. Ann N Y Acad Sci 1119:97–111

    CAS  PubMed  Google Scholar 

  • Jung HJ, Suh Y (2012) MicroRNA in aging: from discovery to biology. Curr Genomics 13(7):548–557

    CAS  PubMed  Google Scholar 

  • Kaarniranta K, Salminen A, Eskelinen EL, Kopitz J (2009) Heat shock proteins as gatekeepers of proteolytic pathways—implications for age-related macular degeneration (AMD). Ageing Res Rev 8(2):128–139

    CAS  PubMed  Google Scholar 

  • Kaelin WG Jr, McKnight SL (2013) Influence of metabolism on epigenetics and disease. Cell 153(1):56–69

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamileri I, Karakasilioti I, Garinis GA (2012) Nucleotide excision repair: new tricks with old bricks. Trends Genet 28(11):566–573

    CAS  PubMed  Google Scholar 

  • Kanungo J (2013) DNA-dependent protein kinase and DNA repair: relevance to Alzheimer’s disease. Alzheimers Res Ther 5(2):13

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464

    CAS  PubMed  Google Scholar 

  • Kern A, Ackermann B, Clement AM, Duerk H, Behl C (2010) HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells of C. elegans. PLoS One 5(1):e8568

    PubMed Central  PubMed  Google Scholar 

  • Kim YJ, Wilson DM 3rd (2012) Overview of base excision repair biochemistry. Curr Mol Pharmacol 5(1):3–13

    Google Scholar 

  • Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, Vassilopoulos A, Ozden O, Park SH, Singh KK, Abdulkadir SA, Spitz DR, Deng CX, Gius D (2010) SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17(1):41–52

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277(5328):942–946.

    Google Scholar 

  • Kirkwood TB (2011) Systems biology of ageing and longevity. Philos Trans R Soc Lond B Biol Sci 366(1561):64–70

    Google Scholar 

  • Kirkwood TB, Austad SN (2000) Why do we age? Nature 408(6809):233–238

    CAS  PubMed  Google Scholar 

  • Klapper W, Parwaresch R, Krupp G (2001) Telomere biology in human aging and aging syndromes. Mech Ageing Dev 122(7):695–712

    CAS  PubMed  Google Scholar 

  • Koshland DE Jr (1992) The molecule of the year. Science 258(5090):1861

    PubMed  Google Scholar 

  • Krokan HE, Bjørås M (2013) Base excision repair. Cold Spring Harb Perspect Biol 5(4):a012583

    PubMed  Google Scholar 

  • Kuro-o M (2012) Klotho in health and disease. Curr Opin Nephrol Hypertens 21(4):362–368

    CAS  PubMed  Google Scholar 

  • Lamy E, Goetz V, Erlacher M, Herz C, Mersch-Sundermann V (2013) hTERT: another brick in the wall of cancer cells. Mutat Res 752(2):119–128

    CAS  PubMed  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    CAS  PubMed  Google Scholar 

  • van Leeuwen FW, de Kleijn DP, van den Hurk HH, Neubauer A, Sonnemans MA, Sluijs JA, Köycü S, Ramdjielal RD, Salehi A, Martens GJ, Grosveld FG, Peter J, Burbach H, Hol EM (1998) Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer’s and down patients. Science 279(5348):242–247

    PubMed  Google Scholar 

  • Lehmann AR, McGibbon D, Stefanini M (2011) Xeroderma pigmentosum. Orphanet J Rare Dis 6:70

    PubMed Central  PubMed  Google Scholar 

  • Li N, Karin M (1999) Is NF-kappaB the sensor of oxidative stress? FASEB J 13(10):1137–1143

    CAS  PubMed  Google Scholar 

  • Lieber MR, Ma Y, Pannicke U, Schwarz K (2003) Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol 4(9):712–720

    CAS  PubMed  Google Scholar 

  • Lieber MR (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79:181–211

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liochev SI (2013) Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med 60:1–4

    CAS  PubMed  Google Scholar 

  • Liscic RM, Breljak D (2011) Molecular basis of amyotrophic lateral sclerosis. Prog Neuropsychopharmacol Biol Psychiatry 35(2):370–372

    CAS  PubMed  Google Scholar 

  • Lombard DB, Chua KF, Mostoslavsky R, Franco S, Gostissa M, Alt FW (2005) DNA repair, genome stability, and aging. Cell 120(4):497–512

    CAS  PubMed  Google Scholar 

  • López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217

    PubMed  Google Scholar 

  • Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429(6994):883–891

    CAS  PubMed  Google Scholar 

  • Marmorstein R, Roth SY (2001) Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev 11(2):155–161

    CAS  PubMed  Google Scholar 

  • Marquardt JU, Fischer K, Baus K, Kashyap A, Ma S, Krupp M, Linke M, Teufel A, Zechner U, Strand D, Thorgeirsson SS, Galle PR, Strand S (2013) SIRT6 dependent genetic and epigenetic alterations are associated with poor clinical outcome in HCC patients. Hepatology 58(3):1054–1064

    Google Scholar 

  • Masters CL, Selkoe DJ (2012) Biochemistry of amyloid \(\upbeta \)-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med 2(6):a006262

    PubMed  Google Scholar 

  • Masui R, Kuramitsu S (2010) Molecular mechanisms of the whole DNA repair system: a comparison of bacterial and eukaryotic systems. J Nucleic Acids 2010:179594

    PubMed Central  PubMed  Google Scholar 

  • Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R (2012) Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489(7415):318–321

    CAS  PubMed  Google Scholar 

  • Mattson MP (2009) Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol 44(10):625–633

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mayer MP, Bukau B (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell Mol Life Sci 62(6):670–684

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ma D, Zhu W, Hu S, Yu X, Yang Y (2013) Association between oxidative stress and telomere length in type 1 and type 2 diabetic patients. J Endocrinol Invest [Epub ahead of print]

    Google Scholar 

  • McCay CM (2000) Is longevity compatible with optimum growth? Science 77(2000):410–411

    Google Scholar 

  • McCollum AK, Casagrande G, Kohn EC (2010) Caught in the middle: the role of Bag3 in disease. Biochem J 425:e1–e3

    CAS  Google Scholar 

  • McCord JM, Fridovich I (2013) Superoxide dismutases: you’ve come a long way, baby. Antioxid Redox Signal [Epub ahead of print]

    Google Scholar 

  • McCord RA, Michishita E, Hong T, Berber E, Boxer LD, Kusumoto R, Guan S, Shi X, Gozani O, Burlingame AL, Bohr VA, Chua KF (2009) SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging 1(1):109–121

    Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244(22):6049–6055

    CAS  PubMed  Google Scholar 

  • McGuinness D, McGuinness DH, McCaul JA, Shiels PG (2011) Sirtuins, bioageing, and cancer. J Aging Res 2011:235754

    CAS  PubMed Central  PubMed  Google Scholar 

  • McKinnon PJ (2012) ATM and the molecular pathogenesis of ataxia telangiectasia. Annu Rev Pathol 7:303–321

    CAS  PubMed  Google Scholar 

  • Meng F, Yao D, Shi Y, Kabakoff J, Wu W, Reicher J, Ma Y, Moosmann B, Masliah E, Lipton SA, Gu Z (2011) Oxidation of the cysteine-rich regions of parkin perturbs its E3 ligase activity and contributes to protein aggregation. Mol Neurodegener 6:34

    CAS  PubMed Central  PubMed  Google Scholar 

  • Merksamer PI, Liu Y, He W, Hirschey MD, Chen D, Verdin E (2013) The sirtuins, oxidative stress and aging: an emerging link. Aging 5(3):144–150

    Google Scholar 

  • Michael R, Bron AJ (2011) The ageing lens and cataract: a model of normal and pathological ageing. Philos Trans R Soc Lond B Biol Sci 366(1568):1278–1292

    CAS  PubMed  Google Scholar 

  • Mocko JB, Kern A, Moosmann B, Behl C, Hajieva P (2010) Phenothiazines interfere with dopaminergic neurodegeneration in Caenorhabditis elegans models of Parkinson’s disease. Neurobiol Dis 40(1):120–129

    CAS  PubMed  Google Scholar 

  • Mogk A, Schmidt R, Bukau B (2007) The N-end rule pathway for regulated proteolysis: prokaryotic and eukaryotic strategies. Trends Cell Biol 17(4):165–172

    CAS  PubMed  Google Scholar 

  • Moore JK, Haber JE (1996) Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae. Mol Cell Biol 16(5):2164–2173

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moosmann B, Behl C (1999) The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc Natl Acad Sci U S A 96(16):8867–8872

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moosmann B, Behl C (2002) Antioxidants as treatment for neurodegenerative disorders. Expert Opin Investig Drugs 11(10):1407–1435

    CAS  PubMed  Google Scholar 

  • Moosmann B, Behl C (2008) Mitochondrially encoded cysteine predicts animal lifespan. Aging Cell 7(1):32–46

    CAS  PubMed  Google Scholar 

  • Morawe T, Hiebel C, Kern A, Behl C (2012) Protein homeostasis aging and Alzheimer’s disease. Mol Neurobiol 46(1):41–54

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382(6591):536–539

    CAS  PubMed  Google Scholar 

  • Mostoslavsky R, Chua KF, Lombard DB, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124(2):315–329

    Google Scholar 

  • Moulson CL, Fong LG, Gardner JM, Farber EA, Go G, Passariello A, Grange DK, Young SG, Miner JH (2007) Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes. Hum Mutat 28(9):882–889

    CAS  PubMed  Google Scholar 

  • Müller-Esterl W (2011) Biochemie: Eine Einführung für Mediziner und Naturwissenschaftler. Spektrum Akademischer Verlag, 2. Auflage

    Google Scholar 

  • Murabito JM, Yuan R, Lunetta KL (2012) The search for longevity and healthy aging genes: insights from epidemiological studies and samples of long-lived individuals. J Gerontol A Biol Sci Med Sci 67(5):470–479

    PubMed  Google Scholar 

  • Nauseef WM (1999) The NADPH-dependent oxidase of phagocytes. Proc Assoc Am Physicians 111(5):373–382

    CAS  PubMed  Google Scholar 

  • Nemoto S, Finkel T (2004) Ageing and the mystery at Arles. Nature 429(6988):149–152

    CAS  PubMed  Google Scholar 

  • Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22(17):R741–752

    Google Scholar 

  • Niedernhofer LJ (2008) Tissue-specific accelerated aging in nucleotide excision repair deficiency. Mech Ageing Dev 129(7–8):408–415

    CAS  PubMed Central  PubMed  Google Scholar 

  • De Oliveira RM, Sarkander J, Kazantsev AG, Outeiro TF (2012) SIRT2 as a therapeutic target for age-related disorders. Front Pharmacol 3:82

    PubMed Central  PubMed  Google Scholar 

  • Olovnikov AM (1996) Telomeres, telomerase, and aging: origin of the theory. Exp Gerontol 31(4):443–448

    CAS  PubMed  Google Scholar 

  • Pamplona R, Barja G (2006) Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection. Biochim Biophys Acta 1757(5–6):496–508

    CAS  PubMed  Google Scholar 

  • Pan MH, Lai CS, Tsai ML, Wu JC, Ho CT (2012) Molecular mechanisms for anti-aging by natural dietary compounds. Mol Nutr Food Res 56(1):88–115

    CAS  PubMed  Google Scholar 

  • Park SY, Lee JH, Ha M, Nam JW, Kim VN (2009) miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol 16(1):23–29

    CAS  PubMed  Google Scholar 

  • Passtoors WM, Beekman M, Deelen J, van der Breggen R, Maier AB, Guigas B, Derhovanessian E, van Heemst D, de Craen AJ, Gunn DA, Pawelec G, Slagboom PE (2013) Gene expression analysis of mTOR pathway: association with human longevity. Aging Cell 12(1):24–31

    CAS  PubMed  Google Scholar 

  • Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, Cota P, Wittnam JL, Gogol-Doering A, Opitz L, Salinas-Riester G, Dettenhofer M, Kang H, Farinelli L, Chen W, Fischer A (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328(5979):753–756

    CAS  PubMed  Google Scholar 

  • Perry JJ, Shin DS, Getzoff ED, Tainer JA (2010) The structural biochemistry of the superoxide dismutases. Biochim Biophys Acta 1804(2):245–262

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pirooznia SK, Elefant F (2013) Targeting specific HATs for neurodegenerative disease treatment: translating basic biology to therapeutic possibilities. Front Cell Neurosci 7:30

    CAS  PubMed Central  PubMed  Google Scholar 

  • Poon HF, Vaishnav RA, Getchell TV, Getchell ML, Butterfield DA (2006) Quantitative proteomics analysis of differential protein expression and oxidative modification of specific proteins in the brains of old mice. Neurobiol Aging 27(7):1010–1019

    CAS  PubMed  Google Scholar 

  • de Pril R, Fischer DF, Maat-Schieman ML, Hobo B, de Vos RA, Brunt ER, Hol EM, Roos RA, van Leeuwen FW (2004) Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases. Hum Mol Genet 13(16):1803–1813

    PubMed  Google Scholar 

  • Qiu J (2006) Epigenetics: unfinished symphony. Nature 441(7090):143–145

    CAS  PubMed  Google Scholar 

  • Ran Q, Liang H, Ikeno Y, Qi W, Prolla TA, Roberts LJ 2nd, Wolf N, Van Remmen H, Richardson A (2007) Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis. J Gerontol A Biol Sci Med Sci 62(9):932–942

    PubMed  Google Scholar 

  • Rao KS (2007) DNA repair in aging rat neurons. Neuroscience 145(4):1330–1340

    CAS  PubMed  Google Scholar 

  • Razzaque MS (2012) The role of Klotho in energy metabolism. Nat Rev Endocrinol 8(10):579–587

    CAS  PubMed Central  PubMed  Google Scholar 

  • Romanov GA, Vanyushin BF (1981) Methylation of reiterated sequences in mammalian DNAs. Effects of the tissue type, age, malignancy and hormonal induction. Biochim Biophys Acta 653(2):204–218

    CAS  PubMed  Google Scholar 

  • Roth GS, Ingram DK, Joseph JA (2007) Nutritional interventions in aging and age-associated diseases. Ann N Y Acad Sci 1114:369–371

    PubMed  Google Scholar 

  • Salih DA, Brunet A (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 20(2):126–136

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schindeldecker M, Stark M, Behl C, Moosmann B (2011) Differential cysteine depletion in respiratory chain complexes enables the distinction of longevity from aerobicity. Mech Ageing Dev 132(4):171–179

    CAS  PubMed  Google Scholar 

  • Schmidt U, Holsboer F, Rein T (2011) Epigenetic aspects of posttraumatic stress disorder. Dis Markers 30(2–3):77–87

    PubMed  Google Scholar 

  • Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT (2012) Genetic signatures of exceptional longevity in humans. PLoS One 7(1):e29848

    CAS  PubMed Central  PubMed  Google Scholar 

  • Seluanov A, Chen Z, Hine C, Sasahara TH, Ribeiro AA, Catania KC, Presgraves DC, Gorbunova V (2007) Telomerase activity coevolves with body mass not lifespan. Aging Cell 6(1):45–52

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shay JW, Wright WE (2007) Hallmarks of telomeres in ageing research. J Pathol 211(2):114–123

    CAS  PubMed  Google Scholar 

  • Shay T, Jojic V, Zuk O, Rothamel K, Puyraimond-Zemmour D, Feng T, Wakamatsu E, Benoist C, Koller D, Regev A, ImmGen Consortium (2013) Conservation and divergence in the transcriptional programs of the human and mouse immune systems. Proc Natl Acad Sci U S A 110(8):2946–2951

    Google Scholar 

  • Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, Eriksson M, Goldman AE, Khuon S, Collins FS, Jenuwein T, Goldman RD (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A 103(23):8703–8708

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sies H (1986) Biochemistry of oxidative stress. Angewandte Chemie Int Ed 12:1058–1071

    Google Scholar 

  • Soto C, Estrada LD (2008) Protein misfolding and neurodegeneration. Arch Neurol 65(2):184–189

    PubMed  Google Scholar 

  • Squier TC (2001) Oxidative stress and protein aggregation during biological aging. Exp Gerontol 36(9):1539–1550

    CAS  PubMed  Google Scholar 

  • Stadtman ER (2006) Protein oxidation and aging. Free Radic Res 40(12):1250–1258

    CAS  PubMed  Google Scholar 

  • Steves CJ, Spector TD, Jackson SH (2012) Ageing, genes, environment and epigenetics: what twin studies tell us now, and in the future. Age Ageing 41(5):581–586

    PubMed  Google Scholar 

  • Strong R, Miller RA, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Harrison DE (2008) Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7(5):641–650

    CAS  PubMed Central  PubMed  Google Scholar 

  • Surova O, Zhivotovsky B (2013) Various modes of cell death induced by DNA damage. Oncogene 32(33):3789–3797

    CAS  PubMed  Google Scholar 

  • Sykora P, Wilson DM 3rd, Bohr VA (2013) Base excision repair in the mammalian brain: implication for age related neurodegeneration. Mech Ageing Dev 134(10):440–448

    Google Scholar 

  • Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci U S A 45(1):30–45

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tam JH, Pasternak SH (2012) Amyloid and Alzheimer’s disease: inside and out. Can J Neurol Sci 39(3):286–298

    PubMed  Google Scholar 

  • Tammen SA, Friso S, Choi SW (2013) Epigenetics: the link between nature and nurture. Mol Aspects Med 34(4):753–764

    CAS  PubMed  Google Scholar 

  • Tan Y, Bush JM, Liu W, Tang F (2009) Identification of longevity genes with systems biology approaches. Adv Appl Bioinform Chem 2:49–56

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tatar M, Khazaeli AA, Curtsinger JW (1997) Chaperoning extended life. Nature 390:30

    CAS  PubMed  Google Scholar 

  • Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292(5514):107–110

    CAS  PubMed  Google Scholar 

  • Tomás-Loba A, Flores I, Fernández-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borrás C, Matheu A, Klatt P, Flores JM, Viña J, Serrano M, Blasco MA (2008) Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135(4):609–622

    PubMed  Google Scholar 

  • Vallabhaneni H, O’Callaghan N, Sidorova J, Liu Y (2013) Defective repair of oxidative base lesions by the DNA glycosylase Nth1 associates with multiple telomere defects. PLoS Genet 9(7):e1003639

    CAS  PubMed Central  PubMed  Google Scholar 

  • Van Raamsdonk JM, Hekimi S (2012) Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci U S A 109(15):5785–5790

    Google Scholar 

  • Vanyushin BF, Nemirovsky LE, Klimenko VV, Vasiliev VK, Belozersky AN (1973b) The 5-methylcytosine in DNA of rats. Tissue and age specificity and the changes induced by hydrocortisone and other agents. Gerontologia 19(3):138–152

    Google Scholar 

  • Vanyushin BF, Mazin AL, Vasilyev VK, Belozersky AN (1973a) The content of 5-methylcytosine in animal DNA: the species and tissue specificity. Biochim Biophys Acta 299(3):397–403

    CAS  PubMed  Google Scholar 

  • Vessoni AT, Filippi-Chiela EC, Menck CF, Lenz G (2013) Autophagy and genomic integrity. Cell Death Differ 20(11):1444–1454

    CAS  PubMed  Google Scholar 

  • Vilenchik MM, Knudson AG Jr (2000) Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates. Proc Natl Acad Sci U S A 97(10):5381–5386

    CAS  PubMed Central  PubMed  Google Scholar 

  • Villalba JM, Alcaín FJ (2012) Sirtuin activators and inhibitors. Biofactors 38(5):349–359

    CAS  PubMed Central  PubMed  Google Scholar 

  • Villalba JM, de Cabo R, Alcain FJ (2012) A patent review of sirtuin activators: an update. Expert Opin Ther Pat 22(4):355–367

    CAS  PubMed  Google Scholar 

  • Vyjayanti VN, Rao KS (2006) DNA double strand break repair in brain: reduced NHEJ activity in aging rat neurons. Neurosci Lett 393(1):18–22

    Google Scholar 

  • Waddington CH (2012) The epigenotype. 1942. Int J Epidemiol 41(1):10–13

    CAS  PubMed  Google Scholar 

  • Weiss EP, Fontana L (2011) Caloric restriction: powerful protection for the aging heart and vasculature. Am J Physiol Heart Circ Physiol 301(4):H1205–H1219

    CAS  PubMed  Google Scholar 

  • Wilkinson KD, Urban MK, Haas AL (1980) Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J Biol Chem 255:7529–7532

    CAS  PubMed  Google Scholar 

  • Witte AV, Fobker M, Gellner R, Knecht S, Flöel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 106(4):1255–1260

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wong AS, Cheung ZH (1812) Ip NY (2011) Molecular machinery of macroautophagy and its deregulation in diseases. Biochim Biophys Acta 11:1490–1497

    Google Scholar 

  • Xiong N, Long X, Xiong J, Jia M, Chen C, Huang J, Ghoorah D, Kong X, Lin Z, Wang T (2012) Mitochondrial complex I inhibitor rotenone-induced toxicity and its potential mechanisms in Parkinson’s disease models. Crit Rev Toxicol 42(7):613–632

    CAS  PubMed  Google Scholar 

  • Xu G, Herzig M, Rotrekl V, Walter CA (2008) Base excision repair, aging and health span. Mech Ageing Dev 129(7–8):366–382

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yakar S, Adamo ML (2012) Insulin-like growth factor 1 physiology: lessons from mouse models. Endocrinol Metab Clin North Am 41(2):231–247

    CAS  PubMed  Google Scholar 

  • Yang Z, Klionsky DJ (2010) Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22:124–131

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yi C, He C (2013) DNA repair by reversal of DNA damage. Cold Spring Harb Perspect Biol 5(1):a012575

    Google Scholar 

  • Yin F, Jiang T, Cadenas E (2013) Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling. Biochem Soc Trans 41(1):101–105

    Google Scholar 

  • Young JC (2010) Mechanisms of the Hsp70 chaperone system. Biochem Cell Biol 88(2):291–300

    Google Scholar 

  • Zentner GE, Henikoff S (2013) Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20(3):259–266

    CAS  PubMed  Google Scholar 

  • Zschocke J, Manthey D, Bayatti N, van der Burg B, Goodenough S, Behl C (2002) Estrogen receptor alpha-mediated silencing of caveolin gene expression in neuronal cells. J Biol Chem 277(41):38772–38780

    CAS  PubMed  Google Scholar 

  • Zuckerman V, Wolyniec K, Sionov RV, Haupt S, Haupt Y (2009) Tumour suppression by p53: the importance of apoptosis and cellular senescence. J Pathol 219(1):3–15

    CAS  PubMed  Google Scholar 

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Behl, C., Ziegler, C. (2014). Theories and Mechanisms of Aging. In: Cell Aging: Molecular Mechanisms and Implications for Disease. SpringerBriefs in Molecular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45179-9_3

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