Skip to main content

Advertisement

SpringerLink
Log in

Biologia dell’invecchiamento

Biology of aging

  • Atti Vicenza 26–27 Maggio 2011
  • Published:
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine

Riassunto

Dagli inizi del XX secolo lo studio dei processi legati all’invecchiamento rappresenta uno degli argomenti più affascinanti della biologia. Numerose teorie furono elaborate per riuscire a comprendere del tutto o parzialmente quale siano i fattori chiave dell’invecchiamento: dalla teoria dei radicali liberi a quella della regolazione genica, dalla teoria della senescenza cellulare all’inflammaging, la definizione di senescenza oggi universalmente accettata è “processo multifattoriale che opera a diversi livelli di organizzazione funzionale”.

Studi condotti sui centenari sani mostrano che sono coinvolte vie di regolazione genetiche che guidano verso un invecchiamento di successo, quali i geni della via dell’insulina/ IGF-1, il gene dell’APO-C e i geni che codificano per citochine pro- e anti-infiammatorie. Parte del meccanismo dell’invecchiamento può essere dovuto al danno cumulativo generato dalle specie reattive dell’ossigeno (ROS), che si traducono in una ridotta capacità del proteasoma di degradare le proteine danneggiate, e dai difetti di riparazione del DNA, anomalie genetiche e fattori ambientali. La relazione tra i cambiamenti legati all’età che producono un fenotipo di invecchiamento sembra avere una comune origine in un processo globale che altera la funzione delle cellule o degli organi. La progressiva incapacità di resistere alle sollecitazioni ambientali rende l’organismo più vulnerabile alle malattie e aumenta il rischio di morte. Riportiamo di seguito le teorie dell’invecchiamento comunemente accettate.

Summary

Since the beginning of the twentieth century the study of processes related to aging has been one of the most fascinating topics in biology. Several theories have been developed to understand the key factors of aging, from free radical theory to gene regulation, from the theory of cellular senescence to inflammaging. The definition of senescence is now universally accepted as a ‘multifactorial process that operates at different levels of functional organization’. Studies in healthy centenarians have shown that genetic regulation pathways are involved in successful aging, including genes via the insulin/IGF-1, AP-C gene and the genes that code for cytokines and pro- and antiinflammatory properties. Some of the mechanisms of aging may be related to cumulative damage generated by reactive oxygen species that results in reduced ability of the proteasome to degrade damaged proteins, and to DNA repair defects, genetic abnormalities and environmental factors. The relationship between the age-related changes that produce an aging phenotype seems to have a common origin in a global process that alters cell and organ function. Indeed, this progressive inability to withstand stresses makes the organism vulnerable to disease increasing the risk of death. In this overview we briefly look at the most commonly accepted theories of aging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Bibliografia

  1. Weinert BT, Timiras PS (2003) Theories of aging. J Appl Physiol 95:1706–1716

    PubMed  CAS  Google Scholar 

  2. Kowald A, Kirkwood TB (1996) A network theory of ageing: the interactions of defective mitochondria, aberrant proteins, free radicals and scavengers in the ageing process. Mutat Res 316:209–236

    PubMed  CAS  Google Scholar 

  3. Franceschi C, Bonafè M, Valensin S et al (2000) Inflammaging-An evolutionary perspective on immunosenescence. Ann N Y Aca Sci 908:244–254

    Article  CAS  Google Scholar 

  4. Harman D (2003) The free radical theory of aging. Antioxid Redox Signal 5:557–561

    Article  PubMed  CAS  Google Scholar 

  5. Ferrara N, Corbi G, Scarpa D et al (2005) The aging theories. G Gerontol 53:57–74

    Google Scholar 

  6. Franceschi C (1989) Cell proliferation, cell death and aging. Aging 1:3–15

    PubMed  CAS  Google Scholar 

  7. Kirkwood TB, Franceschi C (1992) Is aging as complex as it would appear? New perspectives in aging research. Ann N Y Acad. Sci 663:412–417

    Article  PubMed  CAS  Google Scholar 

  8. Medvedev ZA (1990) An attempt at a rational classification of theories of aging. Biol Rev 65:375–398

    Article  PubMed  CAS  Google Scholar 

  9. Pletcher SD, Macdonald SJ, Marguerie R et al (2002) Genomewide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr Biol 12:712–723

    Article  PubMed  CAS  Google Scholar 

  10. Kanungo MS (1975) A model for ageing. J Theor Biol 53:253–261

    Article  PubMed  CAS  Google Scholar 

  11. Finch CE, Ruvkun G (2001) The genetics of aging. Annu Rev Genomics Hum Genet 2:435–462

    Article  PubMed  CAS  Google Scholar 

  12. Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351

    Article  PubMed  CAS  Google Scholar 

  13. Bonafè M, Olivieri F, Mari D et al (1999) P53 codon 72 polymorphism and longevity: additional data on centenarians from continental Italy and Sardinia. Am J Hum Genet 65:1782–1785

    Article  PubMed  Google Scholar 

  14. Franceschi C, Bonafè M (2003) Centenarians as a model for healthy aging, Biochem Soc Trans 31:457–461

    Article  PubMed  CAS  Google Scholar 

  15. McElwee JJ, Schuster E, Blanc E et al (2007) Evolutionary conservation of regulated longevity assurance mechanisms. Genome Biol 8:R132. doi:10.1186/gb-2007-8-7-r132

    Article  PubMed  Google Scholar 

  16. Barbieri, M, Gambardella A, Paolisso G, Varricchio M (2007) Metabolic aspects of the extreme longevity. Exp Gerontol 43:74–78

    Article  PubMed  Google Scholar 

  17. Bartke A (2002) Insulin-like growth factor 1 and mammalian aging. Sci Aging Know Environ 16:vp4. doi: 10.1126/sageke.2002.16.vp4

    Google Scholar 

  18. Russell SJ, Kahn CR (2007) Endocrine regulation of ageing. Nat Rev Mol Cell Biol 8:681–691

    Article  PubMed  CAS  Google Scholar 

  19. Hwangbo DS, Gershman B. Tu MP et al (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429:562–566

    Article  PubMed  CAS  Google Scholar 

  20. Bonafè M, Barbieri M, Marchegiani F (2003) Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab 88:3299–3304

    Article  PubMed  Google Scholar 

  21. Minagawa S, Araya J, Numata T et al (2011) Accelerated Epithelial Cell Senescence in IPF and the Inhibitory Role of SIRT6 in TGF-ta-induced Senescence of Human Bronchial Epithelial Cells. Am J Physiol Lung Cell Mol Physiol 300:L391–L401

    Google Scholar 

  22. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    Article  PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  24. Yang W, Hekimi S (2010) A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLos Biology 8:e1000556. doi: 10.1371/journal.pbio.1000556

    Article  PubMed  Google Scholar 

  25. Brunelle JK, Bell EL, Quesada NM et al (2005) Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab 1:409–414

    Article  PubMed  CAS  Google Scholar 

  26. Van Raamsdonk JM, Hekimi S (2009) Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5:e1000361. doi: 10.1371/journal.pgen.1000361

    Article  PubMed  Google Scholar 

  27. Tower J (2000) Transgenic methods for increasing Drosophila life span. Mech Ageing Dev 118:1–4

    Article  PubMed  CAS  Google Scholar 

  28. Arking R, Burde V, Graves K et al (2000) Forward and reverse selection for longevity in Drosophila is characterized by alteration of antioxidant gene expression and oxidative damage patterns. Exp Gerontol 35:167–185

    Article  PubMed  CAS  Google Scholar 

  29. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    Article  PubMed  CAS  Google Scholar 

  30. Rogina B, Helfand S, Frankel S (2002) Longevity Regulation by Drosophila Rpd3 Deacetylase and Caloric Restriction. Science 298:1745

    Article  PubMed  CAS  Google Scholar 

  31. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 5:59–63

    Article  Google Scholar 

  32. Shringarpure R, Davies KJ (2002) Protein turnover by the proteasome in aging and disease. Free Radic Biol Med 32:1084–1089

    Article  PubMed  CAS  Google Scholar 

  33. Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581

    PubMed  CAS  Google Scholar 

  34. Merry BJ (2002) Molecular mechanisms linking calorie restriction and longevity. Int J Biochem Cell Biol 34:1340–1354

    Article  PubMed  CAS  Google Scholar 

  35. Franceschi C (1989) Cell proliferation, cell death and aging. Aging 1:3–15

    PubMed  CAS  Google Scholar 

  36. Franceschi C, Valensin S, Bonafe M et al (2000) The network and remodelling theories of aging: historical background and new perspectives. Exp Gerontol 35:879–896

    Article  PubMed  CAS  Google Scholar 

  37. Franceschi C, Bonafe M, Valensin S, et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Aca Sci 908:244–254

    Article  CAS  Google Scholar 

  38. George AJ, Ritter MA (1996) Thymic involution with ageing: obsolescence or good housekeeping? Immunol Today 17:267–272

    Article  PubMed  CAS  Google Scholar 

  39. Franceschi C, Monti D, Sansoni P, Cossarizza A (1995) The immunology of exceptional individuals: the lesson of centenarians. Immunol Today 16:12–16

    Article  PubMed  CAS  Google Scholar 

  40. Samani NJ, Boultby R, Butler R et al (2001) Telomere shortening in atherosclerosis. Lancet 358:472–473

    Article  PubMed  CAS  Google Scholar 

  41. Jonasson L, Tompa A, Wikby A (2003) Expansion of peripheral CD8 ? T cells in patients with coronary artery disease: relation to cytomegalovirus infection. J Intern Med 254:472–478

    Article  PubMed  CAS  Google Scholar 

  42. de Boer OJ, Becker AE, van der Wal AC (2003) T lymphocytes in atherogenesis-functional aspects and antigenic repertoire. Cardiovasc Res 60:78–86

    Article  PubMed  Google Scholar 

  43. Pawelek G, Effros C, Caruso C et al (1999) T cells and aging. Front Biosci 4:216–269

    Article  Google Scholar 

  44. Wayne SJ, Rhyne RL, Garry PJ et al (1990) Cell-mediated immunity as predictor of morbidity and mortality in subjects over 60. J Gerontol 45:M45–M48

    PubMed  CAS  Google Scholar 

  45. Campisi J (2003) Cellular Senescence and Cell Death. In: Timiras PS, Physiological Basis of Aging and Geriatrics, 3rd edn. CRC Press, Boca Raton, pp 47–59

    Google Scholar 

  46. Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    Article  PubMed  CAS  Google Scholar 

  47. Campisi J (2000) Cancer, aging and cellular senescence. In Vivo 14:183–188

    PubMed  CAS  Google Scholar 

  48. Blackburn EH (2000) Telomere states and cell fates. Nature 408:53–56

    Article  PubMed  CAS  Google Scholar 

  49. Otani N, Yamakoshi K, Takahashi A, Hara E (2004) The p16INK4A -RB pathway: molecular link between cellular senescence and tumor suppression. J Med Invest 51:146–153

    Article  Google Scholar 

  50. Dimri GP (2005) What has senescence got to do with cancer? Cancer Cell 7:505–512

    Article  PubMed  CAS  Google Scholar 

  51. Maehara K, Yamakoshi K, Otani N et al (2005) Reduction of total E2F/DP activity induces senescent-like cell cycle arrest in cancer cell lacking functional pRb and p53. J Cell Biol 168:553–560

    Article  PubMed  CAS  Google Scholar 

  52. Mason DX, Jackson TJ, Lin AW (2004) Molecular signature of oncogenic ras-induced senescence. Oncogene 23:9238–9246

    PubMed  CAS  Google Scholar 

  53. Collins K (2000) Mammalian telomeres and telomerase. Curr Opin Cell Biol 12:378–383

    Article  PubMed  CAS  Google Scholar 

  54. Wright WE, Piatyszek MA, Rainey WE et al (1996) Telomerase activity in human germline and embryonic tissues and cells. Dev Genet 18:173–179

    Article  PubMed  CAS  Google Scholar 

  55. Kim NW, Piatyszek MA, Prowse KR et al (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015

    Article  PubMed  CAS  Google Scholar 

  56. Reddel RR (2000) The role of senescence and immortalization in carcinogenesis. Carcinogenesis 21:477–484

    Article  PubMed  CAS  Google Scholar 

  57. Ben-Porath I, Weinberg RA (2004) When cells get stressed: an integrative view of cellular senescence. J Clin Invest 113:8–13

    PubMed  CAS  Google Scholar 

  58. Blackburn EH (2000) Telomere states and cell fates. Nature 408:53–56

    Article  PubMed  CAS  Google Scholar 

  59. Donehower LA, Harvey M, Slagle BL et al (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221

    Article  PubMed  CAS  Google Scholar 

  60. Promislow DE (2004) Protein networks, pleiotropy and the evolution of senescence. Proc R Soc Lond B Biol Sci 22:1225–1234

    Article  Google Scholar 

  61. Testa R, Bonfigli AR, Marra M, Testa I (2010) In the light of the metabolic memory theory, should not all aged people with dysglycemia be treated? Rejuvenation Res 13:599–605

    Article  PubMed  Google Scholar 

  62. Paolisso G, Barbieri M, Rizzo MR et al (2001) Low insulin resistance and preserved beta-cell function contribute to human longevity but are not associated with TH-INS genes. Exp Gerontol 37:149–156

    Article  PubMed  CAS  Google Scholar 

  63. Gerstein HC, Yusuf S (1996) Dysglycaemia and risk of cardiovascular disease. Lancet 347:949–950

    Article  PubMed  CAS  Google Scholar 

  64. Gerstein HC (2009) Dysglycemia and cardiovascular risk in the general population. Circulation 119:773–775

    Article  PubMed  Google Scholar 

  65. Wong TY, Liew G, Tapp RJ et al (2008) Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based crosssectional studies. Lancet 371:736–743

    Article  PubMed  CAS  Google Scholar 

  66. Gerstein HC, Pogue J, Mann JF et al (2005) The relationship between dysglycemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis. Diabetologia 48:1749–1755

    Article  PubMed  CAS  Google Scholar 

  67. Diabetes Prevention Program Research Group (2007) The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med 24:137–144

    Article  Google Scholar 

  68. Yashin AI, Ukraintseva SV, Arbeev KG et al (2009) Maintaining physiological state for exceptional survival: What is the normal level of blood glucose and does it change with age? Mech Ageing Dev 130:611–618.

    Article  PubMed  CAS  Google Scholar 

  69. Yashin AI, Arbeev KG, Akushevich I et al (2010) Exceptional survivors have lower age trajectories of blood glucose: lessons from longitudinal data. Biogerontology 11:257–265

    Article  PubMed  Google Scholar 

  70. Ihnat MA, Thorpe JE, Ceriello A (2007) Hypothesis: the “metabolic memory”, the new challenge of diabetes. Diabet Med 24:582–586

    Article  PubMed  CAS  Google Scholar 

  71. The diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986

    Article  Google Scholar 

  72. Writing team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2002) Effect of intensive therapy on the micro-vascular complications of type 1 diabetes mellitus. J Am Med Assoc 287:2563–2569

    Article  Google Scholar 

  73. Writing team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2003) Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephopathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. J Am Med Assoc 290:2159–2167

    Article  Google Scholar 

  74. Nathan DM, Lachin J, Cleary P et al (2003) Diabetes Control and Complications Trial. Epidemiology of Diabetes Interventions and Complications Research Group. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 348:2294–2303

    Article  PubMed  Google Scholar 

  75. Nathan DM, Cleary PA, Backlund JY et al (2005) Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653

    Article  PubMed  Google Scholar 

  76. Colagiuri S, Cull CA, Holman RR; UKPDS Group (2002) Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes? UK prospective diabetes study 61. Diab Care 25:1410–1417

    Article  Google Scholar 

  77. Ceriello A, Esposito K, Piconi L et al (2008) Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 57:1349–1354

    Article  PubMed  CAS  Google Scholar 

  78. Ceriello A, Testa R (2009) Antioxidant anti-inflammatory treatment in type 2 diabetes. Diabetes Care 32:S232–S236

    Article  PubMed  CAS  Google Scholar 

  79. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Metabolic and Nutrition Research Centre on Diabetes, INRCA, Ancona, Italy

    Roberto Testa

  2. Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy

    Fabiola Olivieri & Lucia La Sala

  3. Clinical Pathology and Innovative Therapy, INRCA, Ancona, Italy

    Fabiola Olivieri

  4. Institut d’Investigacions Biomèdique August Pi I Sunyer (IDIBAPS), Barcelona, Spain

    Antonio Ceriello & Lucia La Sala

  5. Centro Ricerche Metaboliche sul Diabete e gli Alimenti, INRCAIRCCS, Via della Montagnola 81, 60131, Ancona, Italy

    Roberto Testa

Authors
  1. Roberto Testa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabiola Olivieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Ceriello
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lucia La Sala
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Testa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Testa, R., Olivieri, F., Ceriello, A. et al. Biologia dell’invecchiamento. Riv Ital Med Lab 7, 65–72 (2011). https://doi.org/10.1007/s13631-011-0010-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13631-011-0010-3

Parole chiave

Key words

Search

Navigation