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Aging of perennial cells and organ parts according to the programmed aging paradigm

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Abstract

If aging is a physiological phenomenon—as maintained by the programmed aging paradigm—it must be caused by specific genetically determined and regulated mechanisms, which must be confirmed by evidence. Within the programmed aging paradigm, a complete proposal starts from the observation that cells, tissues, and organs show continuous turnover: As telomere shortening determines both limits to cell replication and a progressive impairment of cellular functions, a progressive decline in age-related fitness decline (i.e., aging) is a clear consequence. Against this hypothesis, a critic might argue that there are cells (most types of neurons) and organ parts (crystalline core and tooth enamel) that have no turnover and are subject to wear or manifest alterations similar to those of cells with turnover. In this review, it is shown how cell types without turnover appear to be strictly dependent on cells subjected to turnover. The loss or weakening of the functions fulfilled by these cells with turnover, due to telomere shortening and turnover slowing, compromises the vitality of the served cells without turnover. This determines well-known clinical manifestations, which in their early forms are described as distinct diseases (e.g., Alzheimer’s disease, Parkinson’s disease, age-related macular degeneration, etc.). Moreover, for the two organ parts (crystalline core and tooth enamel) without viable cells or any cell turnover, it is discussed how this is entirely compatible with the programmed aging paradigm.

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References

  • Aarsland D, Londos E, Ballard C (2009) Parkinson’s disease dementia and dementia with Lewy bodies: different aspects of one entity. Int Psychogeriatr 21(2):216–219

    Article  PubMed  Google Scholar 

  • Abbott A (2008) The plaque plan. Nature 456:161–164

    Article  CAS  PubMed  Google Scholar 

  • Abbott RD, Ross GW, White LR, Nelson JS, Masaki KH, Tanner CM, Curb JD, Blanchette PL, Popper JS, Petrovitch H (2002) Midlife adiposity and the future risk of Parkinson’s disease. Neurology 59(7):1051–1057

    Article  CAS  PubMed  Google Scholar 

  • Ablonczy Z, Gutierrez DB, Grey AC, Schey KL, Crouch RK (2012) Molecule-specific imaging and quantitation of A2E in the RPE. Adv Exp Med Biol 723. doi:10.1007/978-1-4614-0631-0_11

  • Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu LM, Jacoby R (2009) The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 8:151–157

    Article  CAS  PubMed  Google Scholar 

  • Barnett-Cowan M, Dyde RT, Foxe SH, Moro E, Hutchison WD, Harris LR (2010) Multisensory determinants of orientation perception in Parkinson’s disease. Neuroscience 167(4):1138–1150

    Article  CAS  PubMed  Google Scholar 

  • Barresi M, Ciurleo R, Giacoppo S, Foti Cuzzola V, Celi D, Bramanti P, Marino S (2012) Evaluation of olfactory dysfunction in neurodegenerative diseases. J Neurol Sci 323:16–24

    Article  PubMed  Google Scholar 

  • Ben-Porath I, Weinberg R (2005) The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37:961–976

    Article  CAS  PubMed  Google Scholar 

  • Berger JM, Fine SL, Maguire MG (1999) Age-related macular degeneration. Mosby, USA

    Google Scholar 

  • Bermingham-McDonogh O, Reh TA (2011) Regulated reprogramming in the regeneration of sensory receptor cells. Neuron 71(3):389–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertram L, Blacker D, Mullin K, Keeney D, Jones J, Basu S, Yhu S, McInnis MG, Go RC, Vekrellis K, Selkoe DJ, Saunders AJ, Tanzi RE (2000) Evidence for genetic linkage of Alzheimer’s disease to chromosome 10q. Science 290:2302–2303

    Article  CAS  PubMed  Google Scholar 

  • Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279(5349):349–352

    Article  CAS  PubMed  Google Scholar 

  • Brück D, Wenning GK, Stefanova N, Fellner L (2016) Glia and alpha-synuclein in neurodegeneration: A complex interaction. Neurobiol Dis 85:262–274

  • Buchtova M, Stembirek J, Glocova K, Matalova E, Tucker AS (2012) Early regression of the dental lamina underlies the development of diphyodont dentitions. J Dent Res 91(5):491–498

    Article  CAS  PubMed  Google Scholar 

  • Caballol N, Martí MJ, Tolosa E (2007) Cognitive dysfunction and dementia in Parkinson disease. Mov Disord 22(S17):S358–S366

    Article  PubMed  Google Scholar 

  • Caggiano M, Kauer JS, Hunter DD (1994) Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron 13:339–352

    Article  CAS  PubMed  Google Scholar 

  • Candia OA (2004) Electrolyte and fluid transport across corneal, conjunctival and lens epithelia. Exp Eye Res 78(3):527–535

    Article  CAS  PubMed  Google Scholar 

  • Chen X, Fang H, Schwob JE (2004) Multipotency of purified, transplanted globose basal cells in olfactory epithelium. J Comp Neurol 469:457–474

    Article  PubMed  Google Scholar 

  • Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH (2007) Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ 335(7623):755

    Article  PubMed  PubMed Central  Google Scholar 

  • Counter CM, Hahn WC, Wei W, Caddle SD, Beijersbergen RL, Lansdorp PM, Sedivy JM, Weinberg RA (1998) Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc Natl Acad Sci U S A 95(25):14723–14728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • D’Emic MD, Whitlock JA, Smith KM, Fisher DC, Wilson JA, Evans AR (2013) Evolution of High Tooth Replacement Rates in Sauropod Dinosaurs. PLoS ONE 8(7):e69235

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Davie CA (2008) A review of Parkinson’s disease. Br Med Bull 86(1):109–127

    Article  CAS  PubMed  Google Scholar 

  • de Lau LM, Breteler MM (2006) Epidemiology of Parkinson’s disease. Lancet Neurol 5(6):525–535

    Article  PubMed  Google Scholar 

  • Delcourt C, Cristol JP, Tessier F, Léger CL, Michel F, Papoz L (2000) Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA study. Pathologies Oculaires Liées à l’Age. Am J Epidemiol 151:497–504

    Article  CAS  PubMed  Google Scholar 

  • Dickson DV (2007) Neuropathology of movement disorders. In: Tolosa E. Jankovic JJ. Parkinson’s disease and movement disorders. Lippincott Williams and Wilkins, Hagerstown (MD), pp. 271–283

    Google Scholar 

  • Doty RL (2012) Olfactory dysfunction in Parkinson disease. Nat Rev Neurol 8:329–339

    Article  CAS  PubMed  Google Scholar 

  • Doty RL, Shaman P, Applebaum SL, Giberson R, Siksorski L, Rosenberg L (1984) Smell identification ability: changes with age. Science 226:1441–1443

    Article  CAS  PubMed  Google Scholar 

  • Duff K, McCaffrey RJ, Solomon GS (2002) The Pocket Smell Test: successfully discriminating probable Alzheimer’s dementia from vascular dementia and major depression. J Neuropsychiatry Clin Neurosci 14:197–201

    Article  PubMed  Google Scholar 

  • Duffy VB, Backstrand JR, Ferris AM (1995) Olfactory dysfunction and related nutritional risk in free-living, elderly women. J Am Diet Assoc 95:879–884

    Article  CAS  PubMed  Google Scholar 

  • Ellul J, Archer N, Foy CM, Poppe M, Boothby H, Nicholas H, Brown RG, Lovestone S (2007) The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry 78:233–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Factor SA, Weiner WJ (eds) (2008) Parkinson’s Disease: Diagnosis and Clinical Management, 2nd edn. Demos Medical Publishing, New York, pp. 72–73

    Google Scholar 

  • Fine SL, Berger JW, Maguire MG, Ho AC (2000) Age-related macular degeneration. N Engl J Med 342:483–492

    Article  CAS  PubMed  Google Scholar 

  • Flanary B (2009) Telomeres: function, shortening, and lengthening. In: Telomeres: Function. Shortening and Lengthening. Nova Science Publ. Inc., New York, pp. 379–386

    Google Scholar 

  • Forrester J, Dick A, McMenamin P, Lee W (1996) The Eye: Basic Sciences in Practice. W. B. Saunders Company Ltd., London, London

    Google Scholar 

  • Fossel MB (1996) Reversing human aging. William Morrow and Company, New York

    Google Scholar 

  • Fossel MB (2004) Cells, aging and human disease. Oxford University Press, New York

    Google Scholar 

  • Friedman B, Lahad A, Dresner Y, Vinker S (2013) Long-term statin use and the risk of Parkinson’s disease. Am J Manag Care 19(8):626–632

    PubMed  Google Scholar 

  • Fuenzalida M, Lemus S, Illanes J, Montiel E, Acuña O, Lemus D (2000) Histochemical detection of sugar residues in lizard teeth (Liolaemus gravenhorsti): a lectin-binding study. Biol Res 33(3–4):215–226

    CAS  PubMed  Google Scholar 

  • Gaete M, Tucker AS (2013) Organized emergence of multiple-generations of teeth in snakes is dysregulated by activation of Wnt/beta-catenin signalling. PLoS One 8(9):e74484

  • Galpern WR, Lang AE (2006) Interface between tauopathies and synucleinopathies: a tale of two proteins. Ann Neurol 59(3):449–458

    Article  CAS  PubMed  Google Scholar 

  • Gao X, Simon KC, Schwarzschild MA, Ascherio A (2012) Prospective study of statin use and risk of Parkinson disease. Arch Neurol 69(3):380–384

    Article  PubMed  PubMed Central  Google Scholar 

  • Gorelick PB (2004) Risk factors for vascular dementia and Alzheimer disease. Stroke 35:2620–2622

    Article  PubMed  Google Scholar 

  • Hill K, Hurtado AM (1996) Ache life history. Aldine De Gruyter, New York

    Google Scholar 

  • Hill JM, Zalos G, Halcox JPJ, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600

    Article  PubMed  Google Scholar 

  • Holmes DJ, Austad SN (1995) Birds as animal models for the comparative biology of aging: a prospectus. J Gerontol A Biol Sci 50:B59–B66

    Article  CAS  Google Scholar 

  • Horner PJ, Gage FH (2000) Regenerating the damaged central nervous system. Nature 407:963–970

    Article  CAS  PubMed  Google Scholar 

  • Hu G, Jousilahti P, Nissinen A, Antikainen R, Kivipelto M, Tuomilehto J (2006) Body mass index and the risk of Parkinson disease. Neurology 67(11):1955–1959

    Article  CAS  PubMed  Google Scholar 

  • Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J (2007) Type 2 diabetes and the risk of Parkinson’s disease. Diabetes Care 30(4):842–847

    Article  PubMed  Google Scholar 

  • Huard JM, Youngentob SL, Goldstein BJ, Luskin MB, Schwob JE (1998) Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells. J Comp Neurol 400:469–486

    Article  CAS  PubMed  Google Scholar 

  • Iwai N, Zhou Z, Roop DR, Behringer RR (2008) Horizontal basal cells are multipotent progenitors in normal and injured adult olfactory epithelium. Stem Cells 26(5):1298–1306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358(24):2606–2617

    Article  CAS  PubMed  Google Scholar 

  • Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatr 79(4):368–376

    Article  CAS  PubMed  Google Scholar 

  • Kirkwood TB, Melov S (2011) On the programmed/non-programmed nature of ageing within the life history. Curr Biol 21(18):R701–R707

    Article  CAS  PubMed  Google Scholar 

  • Klein BE, Klein R, Lee KE, Grady LM (2006) Statin use and incident nuclear cataract. JAMA 295:2752–2758

    Article  CAS  PubMed  Google Scholar 

  • Klein R, Deng Y, Klein BE, Hyman L, Seddon J, Frank RN, Wallace RB, Hendrix SL, Kuppermann BD, Langer RD, Kuller L, Brunner R, Johnson KC, Thomas AM, Haan M (2007) Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women’s Health Initiative Sight Exam ancillary study. Am J Ophthalmol 143:473–483

    Article  PubMed  PubMed Central  Google Scholar 

  • Kruman II, Culmsee C, Chan SL, Kruman Y, Guo Z, Penix L, Mattson MP (2000) Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 20(18):6920–6926

    CAS  PubMed  Google Scholar 

  • Kuhn TS (1962) The structure of scientific revolutions. The University of Chicago Press, Chicago

    Google Scholar 

  • Lai SW, Liao KF, Lin CL, Lin CC, Sung FC (2014) Hearing loss may be a non-motor feature of Parkinson’s disease in older people in Taiwan. Eur J Neurol 21(5):752–757

    Article  PubMed  Google Scholar 

  • Leung CT, Coulombe PA, Reed RR (2007) Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci 10:720–726

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Libertini G (2009a) The role of telomere-telomerase system in age-related fitness decline, a tameable process. In: Telomeres: Function, Shortening and Lengthening. Nova Science Publ. Inc., New York, pp. 77–132

    Google Scholar 

  • Libertini G (2009b) Prospects of a longer life span beyond the beneficial effects of a healthy lifestyle. In: handbook on longevity: genetics, Diet & Disease. Nova Science Publ. Inc., New York, pp. 35–95

    Google Scholar 

  • Libertini G (2012) Classification of phenoptotic phenomena. Biochem (Mosc) 77(7):707–715

    Article  CAS  Google Scholar 

  • Libertini G (2014) The programmed aging paradigm: how we get old. Biochem (Mosc) 79(10):1004–1016

    Article  CAS  Google Scholar 

  • Libertini G (2015a) Non-programmed versus programmed aging paradigm. Curr Aging Sci 8(1):56–68

    Article  PubMed  Google Scholar 

  • Libertini G (2015b) Phylogeny of aging and related phenoptotic phenomena. Biochem (Mosc) 80(12):1781–1801

    Article  CAS  Google Scholar 

  • Lin FR, Metter EJ, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L (2011) Hearing loss and incident dementia. Arch Neurol 68(2):214–220

    Article  PubMed  PubMed Central  Google Scholar 

  • Lopez-Real A, Rey P, Soto-Otero R, Mendez-Alvarez E, Labandeira-Garcia JL (2005) Angiotensin-converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6-hydroxydopamine rat model of Parkinsonism. J Neurosci Res 81(6):865–873

    Article  CAS  PubMed  Google Scholar 

  • Maier EC, Saxena A, Alsina B, Bronner ME, Whitfielda TT (2014) Sensational placodes: Neurogenesis in the otic and olfactory systems. Dev Biol 389(1):50–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mares JA, Voland R, Sondel SA, Millen AE, Larowe T, Moeller SM, Klein ML, Blodi BA, Chappell RJ, Tinker L, Ritenbaugh C, Gehrs KM, Sarto GE, Johnson E, Snodderly DM, Wallace RB (2011) Healthy lifestyles related to subsequent prevalence of age-related macular degeneration. Arch Ophthalmol 129(4):470–480

    Article  PubMed  PubMed Central  Google Scholar 

  • Martin GM, Oshima J (2000) Lessons from human progeroid syndromes. Nature 408:263–266

    Article  CAS  PubMed  Google Scholar 

  • Mercer LD, Kelly BL, Horne MK, Beart PM (2005) Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem Pharmacol 69(2):339–345

    Article  CAS  PubMed  Google Scholar 

  • Miners JS, Baig S, Palmer J, Palmer LE, Kehoe PG, Love S (2008) Abeta-degrading enzymes in Alzheimer’s disease. Brain Pathol 18(2):240–252

    Article  CAS  PubMed  Google Scholar 

  • Morales I, Sanchez A, Rodriguez-Sabate C, Rodriguez M (2015) The degeneration of dopaminergic synapses in Parkinson’s disease: a selective animal model. Behav Brain Res 289:19–28

    Article  CAS  PubMed  Google Scholar 

  • Murphy C, Schubert CR, Cruickshanks KJ, Klein BE, Klein R, Nondahl DM (2002) Prevalence of olfactory impairment in older adults. JAMA 288:2307–2312

    Article  PubMed  Google Scholar 

  • Nussey DH, Froy H, Lemaitre JF, Gaillard JM, Austad SN (2013) Senescence in natural populations of animals: widespread evidence and its implications for bio-gerontology. Ageing Res Rev 12:214–225

    Article  PubMed  PubMed Central  Google Scholar 

  • Nuytemans K, Theuns J, Cruts M, Van Broeckhoven C (2010) Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum Mutat 31(7):763–780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Obeso JA, Rodríguez-Oroz MC, Benitez-Temino B, Blesa FJ, Guridi J, Marin C, Rodriguez M (2008) Functional organization of the basal ganglia: therapeutic implications for Parkinson’s disease. Mov Disord 23(Suppl 3):S548–S559

    Article  PubMed  Google Scholar 

  • Obeso JA, Rodriguez-Oroz MC, Goetz CG, Marin C, Kordower JH, Rodriguez M, Hirsch EC, Farrer M, Schapira AH, Halliday G (2010) Missing pieces in the Parkinson’s disease puzzle. Nat Med 16(6):653–661

    Article  CAS  PubMed  Google Scholar 

  • Price WA (1939) Nutrition and Physical Degeneration. Paul B. Hoeber, New York–London

    Google Scholar 

  • Qiu WQ, Walsh DM, Ye Z, Vekrellis K, Zhang J, Podlisny MB, Rosner MR, Safavi A, Hersh LB, Selkoe DJ (1998) Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J Biol Chem 273:32730–32738

    Article  CAS  PubMed  Google Scholar 

  • Rosendorff C, Beeri MS, Silverman JM (2007) Cardiovascular risk factors for Alzheimer’s disease. Am J Geriatr Cardiol 16(3):143–149

    Article  PubMed  Google Scholar 

  • Samii A, Nutt JG, Ransom BR (2004) Parkinson’s disease. Lancet 363(9423):1783–1793

    Article  CAS  PubMed  Google Scholar 

  • Schubert CR, Cruickshanks KJ, Fischer ME, Huang GH, Klein BE, Klein R, Pankow JS, Nondahl DM (2012) Olfactory impairment in an adult population: the Beaver Dam Offspring Study. Chem Senses 37:325–334

    Article  PubMed  PubMed Central  Google Scholar 

  • Schulz-Schaeffer WJ (2010) The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson’s disease and Parkinson’s disease dementia. Acta Neuropathol 120(2):131–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sergeyenko Y, Lall K, Liberman MC, Kujawa SG (2013) Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline. J Neurosci 33:13686–13694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoshani J (2000) Elephants: majestic creatures of the wild. Checkmark Books, New York

    Google Scholar 

  • Single G, Dickman CR, MacDonald DW (2001) Rodents. In: MacDonald DW. Oxford University Press, Oxford, The Encyclopedia of Mammals, pp. 578–587

    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. Biochem (Moscow) 62:1191–1195

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Sonsalla PK, Coleman C, Wong LY, Harris SL, Richardson JR, Gadad BS, Li W, German DC (2013) The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism. Exp Neurol 250:376–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sparrow JR (2003) Therapy for macular degeneration: Insights from acne. Proc Natl Acad Sci U S A 100:4353–4354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sturm E, Stefanova N (2014) Multiple system atrophy: genetic or epigenetic? Exp Neurobiol 23(4):277–291

    Article  PubMed  PubMed Central  Google Scholar 

  • Tassin J, Malaise E, Courtois Y (1979) Human lens cells have an in vitro proliferative capacity inversely proportional to the donor age. Exp Cell Res 123:388–392

    Article  CAS  PubMed  Google Scholar 

  • Tomlinson DR, Gardiner NJ (2008) Glucose neurotoxicity. Nat Rev Neurosci 9(1):36–45

    Article  CAS  PubMed  Google Scholar 

  • Undela K, Gudala K, Malla S, Bansal D (2013) Statin use and risk of Parkinson’s disease: a meta-analysis of observational studies. J Neurol 260(1):158–165

    Article  CAS  PubMed  Google Scholar 

  • Vaziri H (1998) Extension of life span in normal human cells by telomerase activation: a revolution in cultural senescence. J Anti-Aging Med 1:125–130

    Article  CAS  Google Scholar 

  • Vaziri H, Benchimol S (1998) Reconstitution of telomerase activity in normal cells leads to elongation of telomeres and extended replicative life span. Curr Biol 8:279–282

    Article  CAS  PubMed  Google Scholar 

  • Vekrellis K, Ye Z, Qiu WQ, Walsh D, Hartley D, Chesneau V, Rosner MR, Selkoe DJ (2000) Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J Neurosci 20:1657–1665

    CAS  PubMed  Google Scholar 

  • Vitale C, Marcelli V, Allocca R, Santangelo G, Riccardi P, Erro R, Amboni M, Pellecchia MT, Cozzolino A, Longo K, Picillo M, Moccia M, Agosti V, Sorrentino G, Cavaliere M, Marciano E, Barone P (2012) Hearing impairment in Parkinson’s disease: expanding the nonmotor phenotype. Mov Disord 27(12):1530–1535

    Article  PubMed  Google Scholar 

  • Vogel T, Benetos A, Verreault R, Kaltenbach G, Kiesmann M, Berthel M (2006) Risk factors for Alzheimer: towards prevention?] [Article in French. Presse Med 35:1309–1316

    Article  PubMed  Google Scholar 

  • von Zglinicki T, Serra V, Lorenz M, Saretzki G, Lenzen-Grossimlighaus R, Gessner R, Risch A, Steinhagen-Thiessen E (2000) Short telomeres in patients with vascular dementia: an indicator of low antioxidative capacity and a possible risk factor? Lab Investig 80:1739–1747

    Article  Google Scholar 

  • Watt FM, Lo Celso C, Silva-Vargas V (2006) Epidermal stem cells: an update. Curr Opin Genet Dev 16:518–524

    Article  CAS  PubMed  Google Scholar 

  • Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP Jr., Yaffe K (2005) Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ 330(7504):1360–1362

    Article  PubMed  PubMed Central  Google Scholar 

  • Williams RW, Herrup K (1988) The control of neuron number. Annu Rev Neurosc 11(1):423–453

    Article  CAS  Google Scholar 

  • Wong AC, Ryan AF (2015) Mechanisms of sensorineural cell damage, death and survival in the cochlea. Front Aging Neurosci 7:58

    PubMed  PubMed Central  Google Scholar 

  • Woo KS, Chook P, Lolin YI, Cheung AS, Chan LT, Sun YY, Sanderson JE, Metreweli C, Celermajer DS (1997) Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 96:2542–2544

    Article  CAS  PubMed  Google Scholar 

  • Wu P, Wu X, Jiang T-X, Elsey RM, Temple BL, Divers SJ, Glenn TC, Yuan K, Chen M-H, Widelitz RB, Chuon C-M (2013) Specialized stem cell niche enables repetitive renewal of alligator teeth. Proc Natl Acad Sci U S A 110(22):E2009–E2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong AC, Loh TL, Du L, Grati M, Vlajkovic SM, Blanton S, Ryan AF, Chen ZY, Thorne PR, Kachar B, Tekin M, Zhao HB, Housley GD, King MC, Liu XZ (2013) Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci U S A 110:2228–2233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao SC, Hart AD, Terzella MJ (2013) An evidence-based osteopathic approach to Parkinson disease. Osteopath Fam Physician 5(3):96–101

    Article  Google Scholar 

  • Zhan W, Cruickshanks KJ, Klein BE, Klein R, Huang GH, Pankow JS, Gangnon RE, Tweed TS (2010) Generational differences in the prevalence of hearing impairment in older adults. Am J Epidemiol 171:260–266

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang P, Tian B (2014) Metabolic syndrome: an important risk factor for Parkinson’s disease. Oxidative Med Cell Longev 2014:729194

    Google Scholar 

  • Zhao C, Deng W, Gage FH (2008) Mechanisms and functional implications of adult neurogenesis. Cell 132(4):645–660

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Translational Medical Sciences, Federico II University, Naples, Italy

    Giacinto Libertini & Nicola Ferrara

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  1. Giacinto Libertini
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Correspondence to Giacinto Libertini.

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Libertini, G., Ferrara, N. Aging of perennial cells and organ parts according to the programmed aging paradigm. AGE 38, 35 (2016). https://doi.org/10.1007/s11357-016-9895-0

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