Chance and Causality in Ageing and Longevity



The improvement of the quality of life of elderly people is going to become a priority because of the continuous increase in the number of oldest people. This renders the studies of the processes involved in longevity, a complex process influenced by several biological, environmental, and lifestyle factors as well as by chance, of critical importance. Centenarians have been proposed as a model of “positive biology” because they have reached the extreme limits of lifespan, avoiding or delaying major age-related diseases. The identification of the factors that predispose to long and healthy life is of tremendous interest for translational medicine. Here we briefly describe the results obtained so far and their meaning, focusing on the role of chance and causality.


Centenarians Chance Causality Inflamm-ageing Longevity Nutrient-sensing pathways Oxidative stress Physical activity Psychological stress 


  1. 1.
    Ruby JG, Wright KM, Rand KA, Kermany A, Noto K, Curtis D, et al. Estimates of the heritability of human longevity are substantially inflated due to assortative mating. Genetics. 2018;210:1109–24.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Avery P, Barzilai N, Benetos A, Bilianou H, Capri M, Caruso C, et al. Ageing, longevity, exceptional longevity and related genetic and non genetic markers: panel statement. Curr Vasc Pharmacol. 2014;12:659–61.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Dong X, Milholland B, Vijg J. Evidence for a limit to human lifespan. Nature. 2016;538:257–9.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Barbi E, Lagona F, Marsili M, Vaupel JW, Wachter KW. The plateau of human mortality: demography of longevity pioneers. Science. 2018;360:1459–61.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Gavrilov LA, Gavrilova NS. Season of birth and exceptional longevity: comparative study of American centenarians, their siblings, and spouses. J Aging Res. 2011;2011:104616.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Accardi G, Caruso C. Causality and chance in ageing, age-related diseases and longevity. In: Accardi G, Caruso C, editors. Updates in pathobiology: causality and chance in ageing, age-related diseases and longevity. Palermo University Press; 2017. p. 13–23.Google Scholar
  7. 7.
    Caruso C, Passarino G, Puca A, Scapagnini G. “Positive biology”: the centenarian lesson. Immun Ageing. 2012;9:5.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Passarino G, De Rango F, Montesanto A. Human longevity: genetics or lifestyle? It takes two to tango. Immun Ageing. 2016;13:12.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Lutz W, Kebede E. Education and health: redrawing the Preston curve. Popul Dev Rev. 2018;44:343–61.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet. 2009;374:1196–208.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Farrelly C. ‘Positive biology’ as a new paradigm for the medical sciences. Focusing on people who live long, happy, healthy lives might hold the key to improving human well-being. EMBO Rep. 2012;13:186–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Luzzatto L, Pandolfi PP. Causality and chance in the development of cancer. N Engl J Med. 2015;373:84–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Monod J. Le hasard et la nécessité: Essai sur la philosophie naturelle de la biologie moderne, Éditions du Seuil, coll. Points Essais. 1970.Google Scholar
  14. 14.
    Kirkwood TB, Feder M, Finch CE, Franceschi C, Globerson A, Klingenberg CP, et al. What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment? Mech Ageing Dev. 2005;126:439–43.PubMedCrossRefGoogle Scholar
  15. 15.
    Kirkwood TB. Understanding ageing from an evolutionary perspective. J Intern Med. 2008;263:117–27.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kaern M, Elston TC, Blake WJ, Collins JJ. Stochasticity in gene expression: from theories to phenotypes. Nat Rev Genet. 2005;6:451–64.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Losick R, Desplan C. Stochasticity and cell fate. Science. 2008;320:65–8.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Beltrán-Sánchez H, Finch CE, Crimmins EM. Twentieth century surge of excess adult male mortality. Proc Natl Acad Sci U S A. 2015;112:8993–8.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Candore G, Balistreri CR, Colonna-Romano G, Lio D, Listì F, Vasto S, et al. Gender-related immune-inflammatory factors, age-related diseases, and longevity. Rejuvenation Res. 2010;13:292–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Vina J, Gambini J, Lopez-Grueso R, Abdelaziz KM, Jove M, Borras C. Females live longer than males: role of oxidative stress. Curr Pharm Des. 2011;17:3959–65.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Caruso C, Accardi G, Virruso C, Candore G. Sex, gender and immunosenescence: a key to understand the different lifespan between men and women? Immun Ageing. 2013;10:20.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Caruso C, Vasto S. Immunity and aging. In: Ratcliffe MJH, editor. Encyclopedia of immunobiology, vol. 5. Oxford: Academic; 2016. p. 127–32.CrossRefGoogle Scholar
  23. 23.
    Accardi G, Caruso C. Immune-inflammatory responses in the elderly: an update. Immun Ageing. 2018;15:11.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Finch CE, Crimmins EM. Inflammatory exposure and historical changes in human life-spans. Science. 2004;305:1736–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Balistreri CR, Candore G, Caruso C. Role of TLR polymorphisms in aging and age-related diseases. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G, editors. Handbook of immunosenescence. Cham: Springer; 2019. In press.Google Scholar
  26. 26.
    Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing. 2005;2:8.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Candore G, Caruso C, Jirillo E, Magrone T, Vasto S. Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Curr Pharm Des. 2010;16:584–96.PubMedCrossRefGoogle Scholar
  28. 28.
    Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, et al. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine. 2015;2:1549–58.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Storci G, De Carolis S, Papi A, Bacalini MG, Gensous N, Marasco E, et al. Genomic stability, anti-inflammatory phenotype, and up-regulation of the RNAseH2 in cells from centenarians. Cell Death Differ. 2019.
  30. 30.
    De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflammaging. Curr Pharm Des. 2009;15:3003–26.PubMedCrossRefGoogle Scholar
  31. 31.
    Biswas SK. Does the Interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxidative Med Cell Longev. 2016;2016:5698931.CrossRefGoogle Scholar
  32. 32.
    Barja G. Rate of generation of oxidative stress-related damage and animal longevity. Free Radic Biol Med. 2002;33:1167–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Sohal RS, Mockett RJ, Orr WC. Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med. 2002;33:575–86.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757–72.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Bernadotte A, Mikhelson VM, Spivak IM. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence. Aging (Albany NY). 2016;8:3–11.CrossRefGoogle Scholar
  36. 36.
    Rizvi SI, Maurya PK. Alterations in antioxidant enzymes during aging in humans. Mol Biotechnol. 2007;37:58–61.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Gill R, Tsung A, Billiar T. Linking oxidative stress to inflammation: toll-like receptors. Free Radic Biol Med. 2010;48:1121–32.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Marinin F. Signaling by ROS drives inflammasome activation. Eur J Immunol. 2010;40:595–603.CrossRefGoogle Scholar
  39. 39.
    Sharma A, Tate M, Mathew G, Vince JE, Ritchie RH, de Haan JB. Oxidative stress and NLRP3-inflammasome activity as significant drivers of diabetic cardiovascular complications: therapeutic implications. Front Physiol. 2018;9:114.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of beginning). Free Radic Res. 1999;31:261–72.PubMedCrossRefGoogle Scholar
  41. 41.
    Paolisso G, Barbieri M, Bonafè M, Franceschi C. Metabolic age modelling: the lesson from centenarians. Eur J Clin Invest. 2000;30:888–94.PubMedCrossRefGoogle Scholar
  42. 42.
    Mecocci P, Polidori MC, Troiano L, Cherubini A, Cecchetti R, Pini G, et al. Plasma antioxidants and longevity: a study on healthy centenarians. Free Radic Biol Med. 2000;28:1243–8. Erratum in: Free Radic Biol Med. 2000;29:486.PubMedCrossRefGoogle Scholar
  43. 43.
    Polidori MC, Mariani E, Baggio G, Deiana L, Carru C, Pes GM, et al. Different antioxidant profiles in Italian centenarians: the Sardinian peculiarity. Eur J Clin Nutr. 2007;61:922–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G, et al. Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Curr Pharm Des. 2010;16:609–18.PubMedCrossRefGoogle Scholar
  45. 45.
    Vasto S, Buscemi S, Barera A, Di Carlo M, Accardi G, Caruso C. Mediterranean diet and healthy ageing: a Sicilian perspective. Gerontology. 2014;60:508–18.CrossRefGoogle Scholar
  46. 46.
    Aiello A, Accardi G, Candore G, Gambino CM, Mirisola M, Taormina G, et al. Nutrient sensing pathways as therapeutic targets for healthy ageing. Expert Opin Ther Targets. 2017;21:371–80.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Leonardi GC, Accardi G, Monastero R, Nicoletti F, Libra M. Ageing: from inflammation to cancer. Immun Ageing. 2018;15:1.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Dato S, Crocco P, D’Aquila P, de Rango F, Bellizzi D, Rose G, et al. Exploring the role of genetic variability and lifestyle in oxidative stress response for healthy aging and longevity. Int J Mol Sci. 2013;14:16443–72.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, et al. Interventions to slow aging in humans: are we ready? Aging Cell. 2015;14:497–510.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Partridge L. The new biology of ageing. Philos Trans R Soc Lond Ser B Biol Sci. 2010;365:147–54.CrossRefGoogle Scholar
  51. 51.
    Fontana L, Kennedy BK, Longo VD, Seals D, Melov S. Medical research: treat ageing. Nature. 2014;511:405–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1:a001651.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Soultoukis GA, Partridge L. Dietary protein, metabolism, and aging. Annu Rev Biochem. 2016;85:5–34.PubMedCrossRefGoogle Scholar
  54. 54.
    Blumenthal HT. The aging-disease dichotomy: true or false? J Gerontol A Biol Sci Med Sci. 2003;58:138–45.PubMedCrossRefGoogle Scholar
  55. 55.
    Schumacher B, van der Pluijm I, Moorhouse MJ, Kosteas T, Robinson AR, Suh Y, et al. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet. 2008;4:e1000161.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Garinis GA, van der Horst GT, Vijg J, Hoeijmakers JH. DNA damage and ageing: new-age ideas for an age-old problem. Nat Cell Biol. 2008;10:1241–7.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature. 2013;493:338–45.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Di Bona D, Accardi G, Virruso C, Candore G. Caruso l. Association between genetic variations in the insulin/insulin-like growth factor (Igf-1) signaling pathway and longevity: a systematic review and meta-analysis. Curr Vasc Pharmacol. 2014;12:674–81.CrossRefGoogle Scholar
  59. 59.
    Siddle K. Signalling by insulin and IGF receptors: supporting acts and new players. J Mol Endocrinol. 2011;47:R1–10.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13:225–38.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Wątroba M, Szukiewicz D. The role of sirtuins in aging and age related diseases. Adv Med Sci. 2016;61:52–62.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Martin DE, Hall MN. The expanding TOR signaling network. Curr Opin Cell Biol. 2005;17:158–66.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Galluzzi L, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cecconi F, et al. Molecular definitions of autophagy and related processes. EMBO J. 2017;36:1811–36.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Puca AA, Spinelli C, Accardi G, Villa F, Caruso C. Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing. Mech Ageing Dev. 2018;174:95–102.CrossRefGoogle Scholar
  65. 65.
    Accardi G, Aprile S, Candore G, Caruso C, Cusimano R, Cristaldi L, et al. Genotypic and phenotypic aspects of longevity: results from a Sicilian survey and implication for the prevention and the treatment of age-related diseases. Curr Pharm Des. 2019;25:228–35.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Aiello A, Accardi G, Candore G, Carruba G, Davinelli S, Passarino G, et al. Nutrigerontology: a key for achieving successful ageing and longevity. Immun Ageing. 2016;13:17.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Aiello A, Caruso C, Accardi G. Slow-aging diets. In: Danan G, Matthew Dupre E, editors. Encyclopedia of gerontology and population aging. Springer; 2019. In press. Scholar
  68. 68.
    Mirzaei H, Suarez JA, Longo VD. Protein and amino acid restriction, aging and disease: from yeast to humans. Trends Endocrinol Metab. 2014;25:55866.CrossRefGoogle Scholar
  69. 69.
    Fontana L, Partridge L, Longo VD. Extending healthy life span—from yeast to humans. Science. 2010;328:321–6.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Most J, Tosti V, Redman LM, Fontana L. Calorie restriction in humans: an update. Ageing Res Rev. 2017;39:36–45.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Speakman JR, Mitchell SE. Caloric restriction. Mol Asp Med. 2011;32:159–221.CrossRefGoogle Scholar
  72. 72.
    Redman LM, Kraus WE, Bhapkar M, Das SK, Racette SB, Martin CK, et al. Energy requirements in nonobese men and women: results from CALERIE. Am J Clin Nutr. 2014;99:71–8.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Rakowski W, Mor V. The association of physical activity with mortality among older adults in the Longitudinal Study of Aging (1984-1988). J Gerontol. 1992;47:M122–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Warburton DER, Charlesworth S, Ivey A, Nettlefold L, Bredin SSD. A systematic review of the evidence for Canada’s Physical Activity Guidelines for Adults. Int J Behav Nutr Phys Act. 2010;7:39.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Samitz G, Egger M, Zwahlen M. Domains of physical activity and all-cause mortality: systematic review and dose-response meta-analysis of cohort studies. Int J Epidemiol. 2011;40:1382–400.PubMedCrossRefGoogle Scholar
  76. 76.
    Reimers CD, Knapp G, Reimers AK. Does physical activity increase life expectancy? A review of the literature. J Aging Res. 2012;2012:243958.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Garatachea N, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Fiuza-Luces C, Morán M, et al. Exercise attenuates the major hallmarks of aging. Rejuvenation Res. 2015;18:57–89.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Rebelo-Marques A, De Sousa Lages A, Andrade R, Ribeiro CF, Mota-Pinto A, Carrilho F, et al. Aging hallmarks: the benefits of physical exercise. Front Endocrinol (Lausanne). 2018;9:258.CrossRefGoogle Scholar
  80. 80.
    Radák Z, Naito H, Kaneko T, Tahara S, Nakamoto H, Takahashi R, et al. Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle. Pflügers Arch. 2002;445:273–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Gomez-Cabrera M-C, Domenech E, Viña J. Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med. 2008;44:126–31.PubMedCrossRefGoogle Scholar
  82. 82.
    Leick L, Lyngby SS, Wojtasewski JF, Pilegaard H. PGC-1α is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle. Exp Gerontol. 2010;45:336–42.PubMedCrossRefGoogle Scholar
  83. 83.
    Puterman E, Lin J, Blackburn E, O’Donovan A, Adler N, Epel E. The power of exercise: buffering the effect of chronic stress on telomere length. PLoS One. 2010;5:e10837.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Grazioli E, Dimauro I, Mercatelli N, Wang G, Pitsiladis Y, Di Luigi L, et al. Physical activity in the prevention of human diseases: role of epigenetic modifications. BMC Genomics. 2017;18:802.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Perry CG, Lally J, Holloway GP, Heigenhauser GJ, Bonen A, Spriet LL. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle. J Physiol. 2010;588:4795–810.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Nakajima K, Takeoka M, Mori M, Hashimoto S, Sakurai A, Nose H, et al. Exercise effects on methylation of ASC gene. Int J Sports Med. 2010;31:671–5.PubMedCrossRefGoogle Scholar
  87. 87.
    Kim YA, Kim YS, Oh SL, Kim H-J, Song W. Autophagic response to exercise training in skeletal muscle with age. J Physiol Biochem. 2013;69:697–705.PubMedCrossRefGoogle Scholar
  88. 88.
    Yarasheski KE, Pak-Loduca J, Hasten DL, Obert KA, Brown MB, Sinacore DR. Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men ≥ 76 yr old. Am J Physiol Endocrinol Metab. 1999;277:E118–25.CrossRefGoogle Scholar
  89. 89.
    Woods JA, Wilund KR, Martin SA, Kistler BM. Exercise, inflammation and aging. Aging Dis. 2012;3:130–40.PubMedPubMedCentralGoogle Scholar
  90. 90.
    Kokkinos P, Sheriff H, Kheirbek R. Physical inactivity and mortality risk. Cardiol Res Pract. 2011;2011:924945.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Wade KH, Richmond RC, Davey Smith G. Physical activity and longevity: how to move closer to causal inference. Br J Sports Med. 2018;52:890–1.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Kujala UM. Is physical activity a cause of longevity? It is not as straightforward as some would believe. A critical analysis. Br J Sports Med. 2018;52:914–8.PubMedCrossRefGoogle Scholar
  93. 93.
    Brefczynski-Lewis JA, Lutz A, Schaefer HS, Levinson DB, Davidson RJ. Neural correlates of attentional expertise in long-term meditation practitioners. Proc Natl Acad Sci U S A. 2007;104:11483–8.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Gard T, Hölzel BK, Lazar SW. The potential effects of meditation on age-related cognitive decline: a systematic review. Ann N Y Acad Sci. 2014;1307:89–103.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Sharma H. Meditation: process and effects. Ayu. 2015;36:233–7.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Rosenkranz MA, Lutz A, Perlman DM, Bachhuber DR, Schuyler BS, MacCoon DG, et al. Reduced stress and inflammatory responsiveness in experienced meditators compared to a matched healthy control group. Psychoneuroendocrinology. 2016;68:117–25.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Epel E, Blackburn E, Lin J, Dhabhar F, Adler N, Morrow JD, et al. Accelerated telomere shortening in response to exposure to life stress. Proc Natl Acad Sci U S A. 2004;101:17312–5.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Bakaysa SL, Mucci LA, Slagboom E, Boomsma DI, McClearn GE, Johansson B, et al. Telomere length predicts survival independent of genetic influences. Aging Cell. 2007;6:769–74.PubMedCrossRefGoogle Scholar
  99. 99.
    Damjanovic AK, Yang Y, Glaser R, Kiecolt-Glaser JK, Nguyen H, Laskowski B, et al. Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. J Immunol. 2007;179:4249–54.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Hathcock KS, Chiang Y, Hodes RJ. In vivo regulation of telomerase activity and telomere length. Immunol Rev. 2005;205:104–13.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Calabrese J, Baldwin LA. Defining hormesis. Hum Exp Toxicol. 2002;21:91–7.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neurosciences and Advanced DiagnosticsUniversity of PalermoPalermoItaly
  2. 2.Department of Biological, Chemical and Pharmaceutical Sciences and TechnologiesUniversity of PalermoPalermoItaly

Personalised recommendations