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GeroScience

, Volume 40, Issue 3, pp 221–242 | Cite as

The potential of non-myeloablative heterochronous autologous hematopoietic stem cell transplantation for extending a healthy life span

  • Primož Rožman
Review Article

Abstract

Aging is a complex multifactorial process, a prominent component being the senescence of the immune system. Consequently, immune-related diseases develop, including atherosclerosis, cancer, and life-threatening infections, which impact on health and longevity. Rejuvenating the aged immune system could mitigate these diseases, thereby contributing to longevity and health. Currently, an appealing option for rejuvenating the immune system is heterochronous autologous hematopoietic stem cell transplantation (haHSCT), where healthy autologous bone marrow/peripheral blood stem cells are collected during the youth of an individual, cryopreserved, and re-infused when he or she has reached an older age. After infusion, young hematopoietic stem cells can reconstitute the compromised immune system and improve immune function. Several studies using animal models have achieved substantial extension of the life span of animals treated with haHSCT. Therefore, haHSCT could be regarded as a potential procedure for preventing age-related immune defects and extending healthy longevity. In this review, the pros, cons, and future feasibility of this approach are discussed.

Keywords

Immunosenescence Reconstitution Cryopreservation Immune-related diseases of old age Longevity 

Notes

Acknowledgements

I thank Daniel McCloskey and Zoran Ivanović for their critical reading of the manuscript and Thomas Bart for the illustration. The work was supported by the Slovenian Research Agency (Grant No. P3-0371).

Compliance with ethical standards

Conflict of interest

P.R. is a coinventor on a patent on method of providing cellular-based immune enhancement for restoring immunity and preventing age-related diseases (US9867853).

References

  1. Abkowitz JL, Persik MT, Shelton GH, Ott RL, Kiklevich JV, Catlin SN, Guttorp P (1995) Behavior of hematopoietic stem cells in a large animal. Proc Natl Acad Sci U S A 92:2031–2035PubMedPubMedCentralCrossRefGoogle Scholar
  2. Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S (2007) Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178:6912–6922PubMedCrossRefGoogle Scholar
  3. Ahmadi O, McCall JL, Stringer MD (2013) Does senescence affect lymph node number and morphology?A systematic review 54. ANZ J Surg 83:612–618.  https://doi.org/10.1111/ans.12067 PubMedCrossRefGoogle Scholar
  4. Alexander T, Thiel A, Rosen O, Massenkeil G, Sattler A, Kohler S, Mei H, Radtke H, Gromnica-Ihle E, Burmester GR, Arnold R, Radbruch A, Hiepe F (2009) Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood 113:214–223.  https://doi.org/10.1182/blood-2008-07-168286 PubMedCrossRefGoogle Scholar
  5. Alonso-Fernandez P, Puerto M, Mate I, Ribera JM, De la Fuente M (2008) Neutrophils of centenarians show function levels similar to those of young adults. J Am GeriatrSoc 56:2244–2251CrossRefGoogle Scholar
  6. Alvarez E, Ruiz-Gutiérrez V, Sobrino F, Santa-Maria C (2001) Age-related changes in membrane lipid composition, fluidity and respiratory burst in rat peritoneal neutrophils. Clin Exp Immunol 124:95–102PubMedPubMedCentralCrossRefGoogle Scholar
  7. Anisimov VN, Sikora E, Pawelec G (2009) Relationships between cancer and aging: a multilevel approach. Biogerontology 10:323–338PubMedCrossRefGoogle Scholar
  8. Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, von Zglinicki T (2015) Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2:1549–1558.  https://doi.org/10.1016/j.ebiom.2015.07.029 PubMedPubMedCentralCrossRefGoogle Scholar
  9. Arranz L, Fernandez C, Rodriguez A, Ribera JM, De la Fuente M (2008) The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radic Biol Med 45:1252–1262PubMedCrossRefGoogle Scholar
  10. Aspinall R (1997) Age-associated thymic atrophy in the mouse is due to a deficiency affecting rearrangement of the TCR during intrathymic T cell development Journal of immunology (Baltimore, Md: 1950) 158:3037–3045Google Scholar
  11. Aspinall R, Govind S, Lapenna A, Lang PO (2013) Dose response kinetics of CD8 lymphocytes from young animals transfused into old animals and challenged with influenza. Immun Ageing 10:34.  https://doi.org/10.1186/1742-4933-10-34 PubMedPubMedCentralCrossRefGoogle Scholar
  12. Baumgartner WA, Makinodan T, Blahd WH (1980) In vivo evaluation of age-associated changes in delayed-type hypersensitivity. Mech Ageing Dev 12:261–268PubMedCrossRefGoogle Scholar
  13. Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman IL, Bryder D (2010) Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A 107:5465–5470PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bektas A, Schurman SH, Sen R, Ferrucci L (2017) Human T cell immunosenescence and inflammation in aging. J Leukoc Biol 102:977–988.  https://doi.org/10.1189/jlb.3RI0716-335R PubMedCrossRefPubMedCentralGoogle Scholar
  15. Beyret E, Martinez Redondo P, Platero Luengo A, Izpisua Belmonte JC (2018) Elixir of life: thwarting aging with regenerative reprogramming. Circ Res 122:128–141.  https://doi.org/10.1161/CIRCRESAHA.117.311866 PubMedCrossRefGoogle Scholar
  16. Biagi E, Candela M, Fairweather-Tait S, Franceschi C, Brigidi P (2012) Aging of the human metaorganism: the microbial counterpart. Age (Dordr) 34:247–267.  https://doi.org/10.1007/s11357-011-9217-5 CrossRefGoogle Scholar
  17. Biagi E, Candela M, Turroni S, Garagnani P, Franceschi C, Brigidi P (2013) Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res 69:11–20.  https://doi.org/10.1016/j.phrs.2012.10.005 PubMedCrossRefGoogle Scholar
  18. Biagi E, Franceschi C, Rampelli S, Severgnini M, Ostan R, Turroni S, Consolandi C, Quercia S, Scurti M, Monti D, Capri M, Brigidi P, Candela M (2016) Gut microbiota and extreme longevity. Curr Biol 26:1480–1485.  https://doi.org/10.1016/j.cub.2016.04.016 PubMedCrossRefGoogle Scholar
  19. Billen A, Madrigal JA, Shaw BE (2014) A review of the haematopoietic stem cell donation experience: is there room for improvement? Bone Marrow Transplant 49:729–736.  https://doi.org/10.1038/bmt.2013.227 PubMedCrossRefGoogle Scholar
  20. Bitto A, Ito T.K., Pineda V.V., LeTexier N.J., Huang H.Z., Sutlief E., Tung H., Vizzini N., Chen B., Smith K., Meza D., Yajima M., Beyer R.P., Kerr K.F., Davis D.J., Gillespie C.H., Snyder J.M., Treuting P.M., Kaeberlein M. (2016) Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice Elife 5 doi: https://doi.org/10.7554/eLife.16351
  21. Blackburn EH, Epel ES, Lin J (2015) Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science 350:1193–1198.  https://doi.org/10.1126/science.aab3389 PubMedCrossRefPubMedCentralGoogle Scholar
  22. Bodine DM, Seidel NE, Zsebo KM, Orlic D (1993) In vivo administration of stem cell factor to mice increases the absolute number of pluripotent hematopoietic stem cells. Blood 82:445–455PubMedGoogle Scholar
  23. Boehm T, Bleul CC (2007) The evolutionary history of lymphoid organs. Nat Immunol 8:131–135.  https://doi.org/10.1038/ni1435 PubMedCrossRefGoogle Scholar
  24. Borrego F, Alonso MC, Galiani MD, Carracedo J, Ramirez R, Ostos B, Peña J, Solana R (1999) NK phenotypic markers and IL2 response in NK cells from elderly people. Exp Gerontol 34:253–265PubMedCrossRefGoogle Scholar
  25. Boyette LB, Tuan RS (2014) Adult stem cells and diseases of aging. Journal of clinical medicine 3:88–134.  https://doi.org/10.3390/jcm3010088 PubMedPubMedCentralCrossRefGoogle Scholar
  26. Brasel K, McKenna H, Morrissey PJ, Charrier K, Morris AE, Lee CC, Williams DE, Lyman SD (1996) Hematologic effects of flt3 ligand in vivo in mice. Blood 88:2004–2012PubMedGoogle Scholar
  27. Burnet M (2013) Cancer-a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications. Br Med J 1(5023):841–847CrossRefGoogle Scholar
  28. Burt RK, Cohen BA, Russell E, Spero K, Joshi A, Oyama Y, Karpus WJ, Luo K, Jovanovic B, Traynor A, Karlin K, Stefoski D, Burns WH (2003) Hematopoietic stem cell transplantation for progressive multiple sclerosis: failure of a total body irradiation-based conditioning regimen to prevent disease progression in patients with high disability scores. Blood 102:2373–2378.  https://doi.org/10.1182/blood-2003-03-0877 PubMedCrossRefGoogle Scholar
  29. Burt RK, Traynor A, Statkute L, Barr WG, Rosa R, Schroeder J, Verda L, Krosnjar N, Quigley K, Yaung K, Villa Bs M, Takahashi M, Jovanovic B, Oyama Y (2006) Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. Jama 295:527–535.  https://doi.org/10.1001/jama.295.5.527 PubMedCrossRefGoogle Scholar
  30. Butcher SK, Chahal H, Nayak L, Sinclair A, Henriquez NV, Sapey E, O'Mahony D, Lord JM (2001) Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol 70:881–886PubMedGoogle Scholar
  31. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230PubMedCrossRefGoogle Scholar
  32. Charron D (2007) Autologous white blood cell transfusion: toward a younger immunity. HumImmunol 68:805–812Google Scholar
  33. Chen C, Liu Y, Liu Y, Zheng P (2009) mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2:ra75.  https://doi.org/10.1126/scisignal.2000559 PubMedPubMedCentralCrossRefGoogle Scholar
  34. Chen SH, Wang TF, Yang KL (2013) Hematopoietic stem cell donation. Int J Hematol 97:446–455.  https://doi.org/10.1007/s12185-013-1298-8 PubMedCrossRefGoogle Scholar
  35. Cheshier SH, Morrison SJ, Liao X, Weissman IL (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A 96:3120–3125PubMedPubMedCentralCrossRefGoogle Scholar
  36. Chinn IK, Blackburn CC, Manley NR, Sempowski GD (2012) Changes in primary lymphoid organs with aging. SeminImmunol 24:309–320Google Scholar
  37. Cho RH, Sieburg HB, Muller-Sieburg CE (2008) A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 111:5553–5561PubMedPubMedCentralCrossRefGoogle Scholar
  38. Chung HY, Kim HJ, Kim JW, Yu BP (2001) The inflammation hypothesis of aging: molecular modulation by calorie restriction. Ann N Y Acad Sci 928:327–335PubMedCrossRefGoogle Scholar
  39. Columbo M et al (1992) The human recombinant c-kit receptor ligand, rhSCF, induces mediator release from human cutaneous mast cells and enhances IgE-dependent mediator release from both skin mast cells and peripheral blood basophils. J Immunol (Baltimore, Md : 1950) 149:599–608Google Scholar
  40. Conboy IM, Conboy MJ, Rebo J (2015) Systemic problems: a perspective on stem cell aging and rejuvenation. Aging (Albany NY) 7:754–765CrossRefGoogle Scholar
  41. Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354:1813–1826PubMedCrossRefGoogle Scholar
  42. Currais A (2015) Ageing and inflammation—a central role for mitochondria in brain health and disease. Ageing Res Rev 21:30–42.  https://doi.org/10.1016/j.arr.2015.02.001 PubMedCrossRefGoogle Scholar
  43. Dan Dunn J, Alvarez LA, Zhang X, Soldati T (2015) Reactive oxygen species and mitochondria: a nexus of cellular homeostasis. Redox Biol 6:472–485.  https://doi.org/10.1016/j.redox.2015.09.005 PubMedPubMedCentralCrossRefGoogle Scholar
  44. de Kleer I, Vastert B, Klein M, Teklenburg G, Arkesteijn G, Yung GP, Albani S, Kuis W, Wulffraat N, Prakken B (2006) Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network. Blood 107:1696–1702.  https://doi.org/10.1182/blood-2005-07-2800 PubMedCrossRefGoogle Scholar
  45. De la Fuente M (2008) Role of neuroimmunomodulation in aging. Neuroimmunomodulation 15:213–223PubMedCrossRefGoogle Scholar
  46. De la Fuente M et al (2004) Changes with ageing in several leukocyte functions of male and female rats. Biogerontology 5:389–400PubMedCrossRefGoogle Scholar
  47. De la Fuente M, Hernanz A, Vallejo MC (2005) The immune system in the oxidative stress conditions of aging and hypertension: favorable effects of antioxidants and physical exercise. AntioxidRedoxSignal 7:1356–1366Google Scholar
  48. De la Fuente M, Miquel J (2009) An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr PharmDes 15:3003–3026CrossRefGoogle Scholar
  49. de Pooter RF, Cho SK, Carlyle JR, Zuniga-Pflucker JC (2003) In vitro generation of T lymphocytes from embryonic stem cell-derived prehematopoietic progenitors. Blood 102:1649–1653.  https://doi.org/10.1182/blood-2003-01-0224 PubMedCrossRefGoogle Scholar
  50. DelaRosa O, Tarazona R, Casado JG, Alonso C, Ostos B, Pena J, Solana R (2002) Valpha24+ NKT cells are decreased in elderly humans. Exp Gerontol 37:213–217PubMedCrossRefGoogle Scholar
  51. Dolivo DH, Hernandez S, Dominko T (2016) Cellular lifespan and senescence: a complex balance between multiple cellular pathways. Inside the Cell 1:36–46.  https://doi.org/10.1002/icl3.1036 CrossRefGoogle Scholar
  52. Donmez A, Arik B, Tombuloglu M, Cagirgan S (2011) Risk factors for adverse events during collection of peripheral blood stem cells. Transfusion and apheresis science : official journal of the World Apheresis Association: official journal of the European Society for Haemapheresis 45:13–16.  https://doi.org/10.1016/j.transci.2011.06.015 CrossRefGoogle Scholar
  53. Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836–848PubMedCrossRefGoogle Scholar
  54. Dykstra B, Olthof S, Schreuder J, Ritsema M, de Haan G (2011) Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med 208:2691–2703.  https://doi.org/10.1084/jem.20111490 PubMedPubMedCentralCrossRefGoogle Scholar
  55. Egger G, Aigner R, Glasner A, Hofer HP, Mitterhammer H, Zelzer S (2004) Blood polymorphonuclear leukocyte migration as a predictive marker for infections in severe trauma: comparison with various inflammation parameters. Intensive Care Med 30:331–334PubMedCrossRefGoogle Scholar
  56. Egger G, Burda A, Mitterhammer H, Baumann G, Bratschitsch G, Glasner A (2003) Impaired blood polymorphonuclear leukocyte migration and infection risk in severe trauma. The Journal of infection 47:148–154PubMedCrossRefGoogle Scholar
  57. Esparza B, Sanchez H, Ruiz M, Barranquero M, Sabino E, Merino F (1996) Neutrophil function in elderly persons assessed by flow cytometry. Immunol Investig 25:185–190CrossRefGoogle Scholar
  58. Finegold JA, Asaria P, Francis DP (2012) Mortality from ischaemic heart disease by country, region, and age: Statistics from World Health Organisation and United Nations International journal of cardiologyGoogle Scholar
  59. Fortin CF, Lesur O, Fulop T (2007) Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions. FEBS Lett 581:1173–1178PubMedCrossRefGoogle Scholar
  60. Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173–S176PubMedCrossRefGoogle Scholar
  61. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254PubMedCrossRefGoogle Scholar
  62. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105.  https://doi.org/10.1016/j.mad.2006.11.016 PubMedCrossRefGoogle Scholar
  63. Franceschi C, Cossarizza A (1995) Introduction: the reshaping of the immune system with age. Int Rev Immunol 12:1–4PubMedCrossRefGoogle Scholar
  64. Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S (2017) Inflammaging and 'Garb-aging’. Trends Endocrinol Metab 28:199–212.  https://doi.org/10.1016/j.tem.2016.09.005 PubMedCrossRefGoogle Scholar
  65. Franceschi C, Monti D, Barbieri D, Grassilli E, Troiano L, Salvioli S, Negro P, Capri M, Guido M, Azzi R, Sansoni P, Paganelli R, Fagiolo U, Baggio G, Donazzan S, Mariotti S, D'addato S, Gaddi A, Ortolani C, Cossarizza A (1995) Immunosenescence in humans: deterioration or remodelling? Int Rev Immunol 12:57–74PubMedCrossRefGoogle Scholar
  66. Frasca D, Blomberg BB (2009) Effects of aging on B cell function. Curr Opin Immunol 21:425–430PubMedPubMedCentralCrossRefGoogle Scholar
  67. Frasca D, Blomberg BB (2011) Aging impairs murine B cell differentiation and function in primary and secondary lymphoid tissues 67. Aging Dis 2:361–373PubMedPubMedCentralGoogle Scholar
  68. Frasca D, Landin AM, Lechner SC, Ryan JG, Schwartz R, Riley RL, Blomberg BB (2008) Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol 180:5283–5290PubMedCrossRefGoogle Scholar
  69. Frasca D, Riley RL, Blomberg BB (2005) Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans. Semin Immunol 17:378–384PubMedCrossRefGoogle Scholar
  70. Frasca D, Riley RL, Blomberg BB (2007) Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF. Exp Gerontol 42:192–203PubMedCrossRefGoogle Scholar
  71. Fulop T, Dupuis G, Baehl S, le Page A, Bourgade K, Frost E, Witkowski JM, Pawelec G, Larbi A, Cunnane S (2016) From inflamm-aging to immune-paralysis: a slippery slope during aging for immune-adaptation. Biogerontology 17:147–157.  https://doi.org/10.1007/s10522-015-9615-7 PubMedCrossRefGoogle Scholar
  72. Fulop T et al (2017) Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes? Front Immunol 8:1960PubMedCrossRefGoogle Scholar
  73. Fulop T, Larbi A, Kotb R, Pawelec G (2013) Immunology of aging and cancer development 43 InterdiscipTopGerontol 38:38–48Google Scholar
  74. Fulop T, Witkowski JM, Pawelec G, Alan C, Larbi A (2014) On the immunological theory of aging. Interdiscip Top Gerontol 39:163–176.  https://doi.org/10.1159/000358904 PubMedCrossRefGoogle Scholar
  75. Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, Chambert K, Mick E, Neale BM, Fromer M, Purcell SM, Svantesson O, Landén M, Höglund M, Lehmann S, Gabriel SB, Moran JL, Lander ES, Sullivan PF, Sklar P, Grönberg H, Hultman CM, McCarroll SA (2014) Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 371:2477–2487.  https://doi.org/10.1056/NEJMoa1409405 PubMedPubMedCentralCrossRefGoogle Scholar
  76. Giachino C et al (1994) Clonal expansions of V delta 1+ and V delta 2+ cells increase with age and limit the repertoire of human gamma delta T cells. Eur J Immunol 24:1914–1918.  https://doi.org/10.1002/eji.1830240830 PubMedCrossRefGoogle Scholar
  77. Ginaldi L, De MM, Monti D, Franceschi C (2004) The immune system in the elderly: activation-induced and damage-induced apoptosis. ImmunolRes 30:81–94Google Scholar
  78. Gomez CR, Boehmer ED, Kovacs EJ (2005) The aging innate immune system. CurrOpinImmunol 17:457–462Google Scholar
  79. Goodell MA, Rando TA (2015) Stem cells and healthy aging. Science 350:1199–1204.  https://doi.org/10.1126/science.aab3388 PubMedCrossRefGoogle Scholar
  80. Goodman JW, Hodgson GS (1962) Evidence for stem cells in the peripheral blood of mice. Blood 19:702–714PubMedGoogle Scholar
  81. Goronzy JJ, Fulbright JW, Crowson CS, Poland GA, O'Fallon WM, Weyand CM (2001) Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. J Virol 75:12182–12187PubMedPubMedCentralCrossRefGoogle Scholar
  82. Goronzy JJ, Zettl A, Weyand CM (1998) T cell receptor repertoire in rheumatoid arthritis. Int Rev Immunol 17:339–363PubMedCrossRefGoogle Scholar
  83. Gratwohl A (2013) Principles of conditioning. In: EBMT-ESH Handbook on haemopoietic stem cell transplantation. In: Apperley J, Carreras E, Gluckman E, Masszi T (eds) EBMT-ESH handbook on haemopoietic stem Cell Transplant EBMT, Amsterdam, pp 128–144Google Scholar
  84. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, Gratwohl M, Bouzas LF, Confer D, Frauendorfer K, Gluckman E, Greinix H, Horowitz M, Iida M, Lipton J, Madrigal A, Mohty M, Noel L, Novitzky N, Nunez J, Oudshoorn M, Passweg J, van Rood J, Szer J, Blume K, Appelbaum FR, Kodera Y, Niederwieser D, Worldwide Network for Blood and Marrow Transplantation (WBMT) (2015) One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol 2:e91–e100.  https://doi.org/10.1016/S2352-3026(15)00028-9
  85. Grubeck-Loebenstein B, Wick G (2002) The aging of the immune system. Adv Immunol 80:243–284PubMedCrossRefGoogle Scholar
  86. Guidi N, Geiger H (2017) Rejuvenation of aged hematopoietic stem cells. Semin Hematol 54:51–55.  https://doi.org/10.1053/j.seminhematol.2016.10.005 PubMedCrossRefGoogle Scholar
  87. Gupta S (2014) Role of dendritic cells in innate and adaptive immune response in human aging. Exp Gerontol 54:47–52.  https://doi.org/10.1016/j.exger.2013.12.009 PubMedCrossRefGoogle Scholar
  88. Guttorp P, Newton MA, Abkowitz JL (1990) A stochastic model for haematopoiesis in cats. IMA J Math Appl Med Biol 7:125–143PubMedCrossRefGoogle Scholar
  89. Gyurkocza B, Rezvani A, Storb RF (2010) Allogeneic hematopoietic cell transplantation: the state of the art. Expert Rev Hematol 3:285–299PubMedPubMedCentralCrossRefGoogle Scholar
  90. Hadrup SR et al (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol (Baltimore, Md : 1950) 176:2645–2653CrossRefGoogle Scholar
  91. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695.  https://doi.org/10.1056/NEJMra043430 PubMedCrossRefGoogle Scholar
  92. Hare KJ, Jenkinson EJ, Anderson G (1999) In vitro models of T cell development. Semin Immunol 11:3–12.  https://doi.org/10.1006/smim.1998.0151 PubMedCrossRefGoogle Scholar
  93. Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20:145–147PubMedCrossRefGoogle Scholar
  94. Harman D (2003) The free radical theory of aging. Antioxid Redox Signal 5:557–561PubMedCrossRefGoogle Scholar
  95. Hayflick L (2004) The not-so-close relationship between biological aging and age-associated pathologies in humans. J GerontolA BiolSciMedSci 59:B547–B550CrossRefGoogle Scholar
  96. Herbert KE, Levesque JP, Haylock DN, Prince HM (2008) The use of experimental murine models to assess novel agents of hematopoietic stem and progenitor cell mobilization. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 14:603–621.  https://doi.org/10.1016/j.bbmt.2008.02.003 CrossRefGoogle Scholar
  97. Heron M (2015) Deaths: leading causes for 2012, vol 64. National Center for Health Statistics, HyattsvilleGoogle Scholar
  98. Hess DA, Bonde J, Craft TC, Wirthlin L, Hohm S, Lahey R, Todt LM, Dipersio JF, Devine SM, Nolta JA (2007) Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 13:398–411.  https://doi.org/10.1016/j.bbmt.2006.12.445 CrossRefGoogle Scholar
  99. High KP (2004) Infection as a cause of age-related morbidity and mortality. Ageing Res Rev 3:1–14PubMedCrossRefGoogle Scholar
  100. Hölig K (2013) G-CSF in Healthy Allogeneic Stem Cell Donors Transfusion medicine and hemotherapy: offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 40:225–235 doi: https://doi.org/10.1159/000354196
  101. Holstege H, Pfeiffer W, Sie D, Hulsman M, Nicholas TJ, Lee CC, Ross T, Lin J, Miller MA, Ylstra B, Meijers-Heijboer H, Brugman MH, Staal FJT, Holstege G, Reinders MJT, Harkins TT, Levy S, Sistermans EA (2014) Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis. Genome Res 24:733–742.  https://doi.org/10.1101/gr.162131.113 PubMedPubMedCentralCrossRefGoogle Scholar
  102. Honda K, Takenaka K, Shinagawa K, Ishimaru F, Ikeda K, Niiya K, Harada M (2001) Synergistic effects of pegylated recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor on mobilization of hematopoietic progenitor and stem cells with long-term repopulating ability into peripheral blood in mice. Bone Marrow Transplant 28:329–334.  https://doi.org/10.1038/sj.bmt.1703140 PubMedCrossRefGoogle Scholar
  103. Hsu HC, Scott DK, Mountz JD (2005) Impaired apoptosis and immune senescence—cause or effect? ImmunolRev 205:130–146Google Scholar
  104. Hulsdunker J, Zeiser R (2015) Insights into the pathogenesis of GvHD: what mice can teach us about man. Tissue Antigens 85:2–9.  https://doi.org/10.1111/tan.12497 PubMedCrossRefGoogle Scholar
  105. Iwasaki A, Medzhitov R (2015) Control of adaptive immunity by the innate immune system. Nat Immunol 16:343–353PubMedPubMedCentralCrossRefGoogle Scholar
  106. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, Lindsley RC, Mermel CH, Burtt N, Chavez A, Higgins JM, Moltchanov V, Kuo FC, Kluk MJ, Henderson B, Kinnunen L, Koistinen HA, Ladenvall C, Getz G, Correa A, Banahan BF, Gabriel S, Kathiresan S, Stringham HM, McCarthy MI, Boehnke M, Tuomilehto J, Haiman C, Groop L, Atzmon G, Wilson JG, Neuberg D, Altshuler D, Ebert BL (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371:2488–2498.  https://doi.org/10.1056/NEJMoa1408617 PubMedPubMedCentralCrossRefGoogle Scholar
  107. Jazbec K, Jež M, Smrekar B, Miceska S, Rožman JŽ, Švajger U, Završnik J, Malovrh T, Rožman P (2018) Chimerism and gene therapy—lessons learned from non-conditioned murine bone marrow transplantation models. Eur J Haematol 100:372–382.  https://doi.org/10.1111/ejh.13024 PubMedCrossRefGoogle Scholar
  108. Kaeberlein M, Rabinovitch PS, Martin GM (2015) Healthy aging: the ultimate preventative medicine. Science 350:1191–1193.  https://doi.org/10.1126/science.aad3267 PubMedPubMedCentralCrossRefGoogle Scholar
  109. Kamminga LM, van Os R, Ausema A, Noach EJK, Weersing E, Dontje B, Vellenga E, de Haan G (2005) Impaired hematopoietic stem cell functioning after serial transplantation and during normal aging. Stem Cells 23:82–92PubMedCrossRefGoogle Scholar
  110. Kaufmann SHE, Dorhoi A (2016) Molecular determinants in phagocyte-bacteria interactions. Immunity 44:476–491.  https://doi.org/10.1016/j.immuni.2016.02.014 PubMedCrossRefGoogle Scholar
  111. Khan M, Mohsin S, Khan SN, Riazuddin S (2011) Repair of senescent myocardium by mesenchymal stem cells is dependent on the age of donor mice. JCell MolMed 15:1515–1527Google Scholar
  112. Kim D, Kyung J, Park D, Choi EK, Kim KS, Shin K, Lee H, Shin IS, Kang SK, Ra JC, Kim YB (2015) Health span-extending activity of human amniotic membrane- and adipose tissue-derived stem cells in F344 rats. Stem Cells Transl Med 4:1–11.  https://doi.org/10.5966/sctm.2015-0011 CrossRefGoogle Scholar
  113. King AG, Horowitz D, Dillon SB, Levin R, Farese AM, MacVittie TJ, Pelus LM (2001) Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GRObeta. Blood 97:1534–1542PubMedCrossRefGoogle Scholar
  114. Klein L, Hinterberger M, Wirnsberger G, Kyewski B (2009) Antigen presentation in the thymus for positive selection and central tolerance induction. Nat Rev Immunol 9:833–844.  https://doi.org/10.1038/nri2669 PubMedCrossRefGoogle Scholar
  115. Kollman C (2001) Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 98:2043–2051PubMedCrossRefGoogle Scholar
  116. Kollman C et al (2016) The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy. Blood 127:260–267.  https://doi.org/10.1182/blood-2015-08-663823 PubMedPubMedCentralCrossRefGoogle Scholar
  117. Kopp EB, Medzhitov R (2009) Infection and inflammation in somatic maintenance, growth and longevity. Evol Appl 2:132–141PubMedPubMedCentralCrossRefGoogle Scholar
  118. Kovina MV, Zuev VA, Kagarlitskiy GO, Khodarovich YM (2013) Effect on lifespan of high yield non-myeloablating transplantation of bone marrow from young to old mice. Front Genet 4:144PubMedPubMedCentralCrossRefGoogle Scholar
  119. Kritchevsky SB, Cesari M, Pahor M (2005) Inflammatory markers and cardiovascular health in older adults. Cardiovasc Res 66:265–275PubMedCrossRefGoogle Scholar
  120. Lakatta EG, Levy D (2003) Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation 107:139–146PubMedCrossRefGoogle Scholar
  121. Lang PO, Govind S, Aspinall R (2013) Reversing T cell immunosenescence: why, who, and how 70 Age (Dordr) 35:609–620Google Scholar
  122. Lang PO, Mitchell WA, Govind S, Aspinall R (2011) Real time-PCR assay estimating the naive T-cell pool in whole blood and dried blood spot samples: pilot study in young adults. J Immunol Methods 369:133–140.  https://doi.org/10.1016/j.jim.2011.05.002 PubMedCrossRefGoogle Scholar
  123. Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G (2008) Aging of the immune system as a prognostic factor for human longevity Physiology (Bethesda, Md) 23:64–74Google Scholar
  124. Laterveer L, Lindley IJ, Hamilton MS, Willemze R, Fibbe WE (1995) Interleukin-8 induces rapid mobilization of hematopoietic stem cells with radioprotective capacity and long-term myelolymphoid repopulating ability. Blood 85:2269–2275PubMedGoogle Scholar
  125. Lavasani M, Robinson AR, Lu A, Song M, Feduska JM, Ahani B, Tilstra JS, Feldman CH, Robbins PD, Niedernhofer LJ, Huard J (2012) Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 3:608–608PubMedPubMedCentralCrossRefGoogle Scholar
  126. Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B (2005) Age-related loss of naive T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology 114:37–43PubMedPubMedCentralCrossRefGoogle Scholar
  127. Li L, Hsu HC, William GE, Stockard CR, Ho KJ, Lott P, Yang PA, Zhang HG, Mountz JD (2003) Cellular mechanism of thymic involution. Scand J Immunol 57:410–422PubMedCrossRefGoogle Scholar
  128. Li Y, Hisha H, Inaba M, Lian Z, Yu C, Kawamura M, Yamamoto Y, Nishio N, Toki J, Fan H, Ikehara S (2000) Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: a role of stromal cells in positive selection. Exp Hematol 28:950–960PubMedCrossRefGoogle Scholar
  129. Listi F et al (2006) A study of serum immunoglobulin levels in elderly persons that provides new insights into B cell immunosenescence. Ann N Y Acad Sci 1089:487–495PubMedCrossRefGoogle Scholar
  130. Liu JP (2014) Molecular mechanisms of ageing and related diseases. Clin Exp Pharmacol Physiol 41:445–458.  https://doi.org/10.1111/1440-1681.12247 PubMedCrossRefGoogle Scholar
  131. Longo VD, Antebi A, Bartke A, Barzilai N, Brown-Borg HM, Caruso C, Curiel TJ, de Cabo R, Franceschi C, Gems D, Ingram DK, Johnson TE, Kennedy BK, Kenyon C, Klein S, Kopchick JJ, Lepperdinger G, Madeo F, Mirisola MG, Mitchell JR, Passarino G, Rudolph KL, Sedivy JM, Shadel GS, Sinclair DA, Spindler SR, Suh Y, Vijg J, Vinciguerra M, Fontana L (2015) Interventions to slow aging in humans: are we ready? Aging Cell 14:497–510.  https://doi.org/10.1111/acel.12338 PubMedPubMedCentralCrossRefGoogle Scholar
  132. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217.  https://doi.org/10.1016/j.cell.2013.05.039 PubMedPubMedCentralCrossRefGoogle Scholar
  133. Lord JM, Butcher S, Killampali V, Lascelles D, Salmon M (2001) Neutrophil ageing and immunesenescence. Mech Ageing Dev 122:1521–1535PubMedCrossRefGoogle Scholar
  134. Mancardi G, Saccardi R (2008) Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol 7:626–636.  https://doi.org/10.1016/S1474-4422(08)70138-8 PubMedCrossRefGoogle Scholar
  135. Mannick JB, del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, Lonetto MA, Maecker HT, Kovarik J, Carson S, Glass DJ, Klickstein LB (2014) mTOR inhibition improves immune function in the elderly. Sci Transl Med 6:268ra179.  https://doi.org/10.1126/scitranslmed.3009892 PubMedCrossRefGoogle Scholar
  136. Manz RA, Thiel A, Radbruch A (1997) Lifetime of plasma cells in the bone marrow. Nature 388:133–134PubMedCrossRefGoogle Scholar
  137. McCurdy SR et al (2018) Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide. Blood Adv 2:299–307.  https://doi.org/10.1182/bloodadvances.2017014829 PubMedPubMedCentralCrossRefGoogle Scholar
  138. McGeer EG, McGeer PL (1999) Brain inflammation in Alzheimer disease and the therapeutic implications. Curr Pharm Des 5:821–836PubMedGoogle Scholar
  139. Mehta J, Gordon LI, Tallman MS, Winter JN, Evens AO, Frankfurt O, Williams SF, Grinblatt D, Kaminer L, Meagher R, Singhal S (2006) Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially? Bone Marrow Transplant 38:95–100.  https://doi.org/10.1038/sj.bmt.1705388 PubMedCrossRefGoogle Scholar
  140. Miller RA (1996) The aging immune system: primer and prospectus. Science 273:70–74PubMedCrossRefGoogle Scholar
  141. Moalic V (2013) Mobilization and collection of peripheral blood stem cells in healthy donors: risks, adverse events and follow-up. Pathologie-Biologie 61:70–74.  https://doi.org/10.1016/j.patbio.2012.10.003 PubMedCrossRefGoogle Scholar
  142. Molony RD, Malawista A, Montgomery RR (2017a) Reduced dynamic range of antiviral innate immune responses in aging Exp Gerontol doi: https://doi.org/10.1016/j.exger.2017.08.019
  143. Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A (2017b) Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Sci Signal 10:eaan2392.  https://doi.org/10.1126/scisignal.aan2392 PubMedCrossRefGoogle Scholar
  144. Moskalev A, Anisimov V, Aliper A, Artemov A, Asadullah K, Belsky D, Baranova A, de Grey A, Dixit VD, Debonneuil E, Dobrovolskaya E, Fedichev P, Fedintsev A, Fraifeld V, Franceschi C, Freer R, Fülöp T, Feige J, Gems D, Gladyshev V, Gorbunova V, Irincheeva I, Jager S, Jazwinski SM, Kaeberlein M, Kennedy B, Khaltourina D, Kovalchuk I, Kovalchuk O, Kozin S, Kulminski A, Lashmanova E, Lezhnina K, Liu GH, Longo V, Mamoshina P, Maslov A, Pedro de Magalhaes J, Mitchell J, Mitnitski A, Nikolsky Y, Ozerov I, Pasyukova E, Peregudova D, Popov V, Proshkina E, Putin E, Rogaev E, Rogina B, Schastnaya J, Seluanov A, Shaposhnikov M, Simm A, Skulachev V, Skulachev M, Solovev I, Spindler S, Stefanova N, Suh Y, Swick A, Tower J, Gudkov AV, Vijg J, Voronkov A, West M, Wagner W, Yashin A, Zemskaya N, Zhumadilov Z, Zhavoronkov A (2017) A review of the biomedical innovations for healthy longevity. Aging (Albany NY) 9:7–25.  https://doi.org/10.18632/aging.101163 CrossRefGoogle Scholar
  145. Muraro PA, Martin R, Mancardi GL, Nicholas R, Sormani MP, Saccardi R (2017) Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol 13:391–405.  https://doi.org/10.1038/nrneurol.2017.81 PubMedCrossRefGoogle Scholar
  146. Niwa Y, Kasama T, Miyachi Y, Kanoh T (1989) Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci 44:1655–1664PubMedCrossRefGoogle Scholar
  147. Ogata K, An E, Shioi Y, Nakamura K, Luo S, Yokose N, Minami S, Dan K (2001) Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol 124:392–397PubMedPubMedCentralCrossRefGoogle Scholar
  148. Okin D, Medzhitov R (2012) Evolution of inflammatory diseases. Curr Biol 22:R733–R740PubMedPubMedCentralCrossRefGoogle Scholar
  149. Ortega E, Garcia JJ, De la Fuente M (2000) Ageing modulates some aspects of the non-specific immune response of murine macrophages and lymphocytes. Exp Physiol 85:519–525PubMedCrossRefGoogle Scholar
  150. Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E, Monti D, Franceschi C (2008) Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation 15:224–240PubMedCrossRefGoogle Scholar
  151. Pamphilon D, Siddiq S, Brunskill S, Doree C, Hyde C, Horowitz M, Stanworth S (2009) Stem cell donation—what advice can be given to the donor? Br J Haematol 147:71–76.  https://doi.org/10.1111/j.1365-2141.2009.07832.x PubMedPubMedCentralCrossRefGoogle Scholar
  152. Papayannopoulou T (2004) Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization. Blood 103:1580–1585.  https://doi.org/10.1182/blood-2003-05-1595 PubMedCrossRefGoogle Scholar
  153. Passweg JR et al (2013) Hematopoietic SCT in Europe: data and trends in 2011 4. Bone Marrow Transplant 48:1161–1167PubMedPubMedCentralCrossRefGoogle Scholar
  154. Pawelec G, Goldeck D, Derhovanessian E (2014) Inflammation, ageing and chronic disease. Curr Opin Immunol 29:23–28.  https://doi.org/10.1016/j.coi.2014.03.007 PubMedCrossRefGoogle Scholar
  155. Pawelec G, Koch S, Griesemann H, Rehbein A, Hahnel K, Gouttefangeas C (2006) Immunosenescence, suppression and tumour progression. Cancer immunology, immunotherapy: CII 55:981–986 doi: https://doi.org/10.1007/s00262-005-0109-3,
  156. Peralbo E, DelaRosa O, Gayoso I, Pita ML, Tarazona R, Solana R (2006) Decreased frequency and proliferative response of invariant Valpha24Vbeta11 natural killer T (iNKT) cells in healthy elderly. Biogerontology 7:483–492.  https://doi.org/10.1007/s10522-006-9063-5 PubMedCrossRefGoogle Scholar
  157. Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ (2004) Aging and innate immune cells. J Leukoc Biol 76:291–299PubMedCrossRefGoogle Scholar
  158. Potter JM, O'Donnel B, Carman WF, Roberts MA, Stott DJ (1999) Serological response to influenza vaccination and nutritional and functional status of patients in geriatric medical long-term care. Age Ageing 28:141–145PubMedCrossRefGoogle Scholar
  159. Pulsipher MA, Chitphakdithai P, Logan BR, Navarro WH, Levine JE, Miller JP, Shaw BE, O’Donnell PV, Majhail NS, Confer DL (2014) Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation. Blood 123:3655–3663.  https://doi.org/10.1182/blood-2013-12-542464 PubMedPubMedCentralCrossRefGoogle Scholar
  160. Quesenberry PJ, Stewart MF, Peters S, Nillson S, Rao S, Tiarks C, Zhong S, Frimberger A, Reilly J, Ramshaw H (1997) Engraftment of hematopoietic stem cells in nonmyeloablated and myeloablated hosts. Stem Cells 15(Suppl 1):167–169PubMedCrossRefGoogle Scholar
  161. Rao SS, Peters SO, Crittenden RB, Stewart FM, Ramshaw HS, Quesenberry PJ (1997) Stem cell transplantation in the normal nonmyeloablated host: relationship between cell dose, schedule, and engraftment. ExpHematol 25:114–121Google Scholar
  162. Rivera A, Siracusa MC, Yap GS, Gause WC (2016) Innate cell communication kick-starts pathogen-specific immunity. Nat Immunol 17:356–363.  https://doi.org/10.1038/ni.3375 PubMedPubMedCentralCrossRefGoogle Scholar
  163. Rosen O, Thiel A, Massenkeil G, Hiepe F, Häupl T, Radtke H, Burmester GR, Gromnica-Ihle E, Radbruch A, Arnold R (2000) Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells. Arthritis Res 2:327–336.  https://doi.org/10.1186/ar107 PubMedPubMedCentralCrossRefGoogle Scholar
  164. Rosenberg C, Bovin NV, Bram LV, Flyvbjerg E, Erlandsen M, Vorup-Jensen T, Petersen E (2013) Age is an important determinant in humoral and T cell responses to immunization with hepatitis B surface antigen 35. HumVaccinImmunother 9:1466–1476.  https://doi.org/10.4161/hv.24480 CrossRefGoogle Scholar
  165. Rosenberg SA, Sports C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, Stetler-Stevenson M, Morton KE, Mavroukakis SA, Morre M, Buffet R, Mackall CL, Gress RE (2006) IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother 29:313–319PubMedPubMedCentralCrossRefGoogle Scholar
  166. Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ, Weissman IL (2005) Cell intrinsic alterations underlie hematopoietic stem cell aging. ProcNatlAcadSciUSA 102:9194–9199CrossRefGoogle Scholar
  167. Roy S, Sen CK, Kobuchi H, Packer L (1998) Antioxidant regulation of phorbol ester-induced adhesion of human Jurkat T-cells to endothelial cells. Free Radic Biol Med 25:229–241PubMedCrossRefGoogle Scholar
  168. Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L, Telera A, Lucchini G, Passeri G, Monti D, Franceschi C, Passeri M (2008) The immune system in extreme longevity. Exp Gerontol 43:61–65PubMedCrossRefGoogle Scholar
  169. Santoro A, Ostan R, Candela M, Biagi E, Brigidi P, Capri M, Franceschi C (2018) Gut microbiota changes in the extreme decades of human life: a focus on centenarians. Cell Mol Life Sci 75:129–148.  https://doi.org/10.1007/s00018-017-2674-y PubMedCrossRefGoogle Scholar
  170. Schultz MB, Sinclair DA (2016) When stem cells grow old: phenotypes and mechanisms of stem cell aging. Development 143:3–14.  https://doi.org/10.1242/dev.130633 PubMedPubMedCentralCrossRefGoogle Scholar
  171. Scudellari M (2015) Ageing research: blood to blood. Nature 517:426–429.  https://doi.org/10.1038/517426a PubMedCrossRefGoogle Scholar
  172. Sebastian C, Espia M, Serra M, Celada A, loberas J (2005) MacrophAging: a cellular and molecular review. Immunobiology 210:121–126PubMedCrossRefGoogle Scholar
  173. Selesniemi K, Lee HJ, Niikura T, Tilly JL (2009) Young adult donor bone marrow infusions into female mice postpone age-related reproductive failure and improve offspring survival. Aging 1:49–57CrossRefGoogle Scholar
  174. Sharpless NE, Depinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8:703–713PubMedCrossRefGoogle Scholar
  175. Sharpless NE, Schatten G (2009) Stem cell aging. JGerontolA BiolSciMedSci 64:202–204Google Scholar
  176. Shaw BE, Confer DL, Hwang W, Pulsipher MA (2015) A review of the genetic and long-term effects of G-CSF injections in healthy donors: a reassuring lack of evidence for the development of haematological malignancies. Bone Marrow Transplant 50:334–340.  https://doi.org/10.1038/bmt.2014.278 PubMedCrossRefGoogle Scholar
  177. Shen J, Tsai YT, Dimarco NM, Long MA, Sun X, Tang L (2011) Transplantation of mesenchymal stem cells from young donors delays aging in mice. SciRep 1:67Google Scholar
  178. Shepherd BE, Kiem HP, Lansdorp PM, Dunbar CE, Aubert G, LaRochelle A, Seggewiss R, Guttorp P, Abkowitz JL (2007) Hematopoietic stem-cell behavior in nonhuman primates. Blood 110:1806–1813.  https://doi.org/10.1182/blood-2007-02-075382 PubMedPubMedCentralCrossRefGoogle Scholar
  179. Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K (2005) Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol 175:3262–3267PubMedCrossRefGoogle Scholar
  180. Shlush LI (2018) Age-related clonal hematopoiesis blood 131:496–504Google Scholar
  181. Shu Z, Heimfeld S, Gao D (2014) Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion. Bone Marrow Transplant 49:469–476.  https://doi.org/10.1038/bmt.2013.152 PubMedCrossRefGoogle Scholar
  182. Solana R, Pawelec G, Tarazona R (2006) Aging and innate immunity. Immunity 24:491–494PubMedCrossRefGoogle Scholar
  183. Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T (2012) Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans 50. SeminImmunol 24:331–341Google Scholar
  184. Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, Mancardi GL (2017) Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology 88:2115–2122.  https://doi.org/10.1212/WNL.0000000000003987 PubMedCrossRefGoogle Scholar
  185. Sportès C et al (2010) Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res 16:727–735PubMedPubMedCentralCrossRefGoogle Scholar
  186. Sportès C, Hakim FT, Memon SA, Zhang H, Chua KS, Brown MR, Fleisher TA, Krumlauf MC, Babb RR, Chow CK, Fry TJ, Engels J, Buffet R, Morre M, Amato RJ, Venzon DJ, Korngold R, Pecora A, Gress RE, Mackall CL (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205:1701–1714PubMedPubMedCentralCrossRefGoogle Scholar
  187. Stephan RP, Sanders VM, Witte PL (1996) Stage-specific alterations in murine B lymphopoiesis with age. Int Immunol 8:509–518PubMedCrossRefGoogle Scholar
  188. Stewart FM, Crittenden RB, Lowry PA, Pearson-White S, Quesenberry PJ (1993) Long-term engraftment of normal and post-5-fluorouracil murine marrow into normal nonmyeloablated mice. Blood 81:2566–2571PubMedGoogle Scholar
  189. Tabas I, Lichtman AH (2017) Monocyte-macrophages and T cells in atherosclerosis. Immunity 47:621–634PubMedPubMedCentralCrossRefGoogle Scholar
  190. Takaki T, Hosaka N, Miyake T, Cui W, Nishida T, Inaba M, Ikehara S (2008) Presence of donor-derived thymic epithelial cells in [B6-->MRL/lpr] mice after allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT). J Autoimmun 31:408–415.  https://doi.org/10.1016/j.jaut.2008.09.003 PubMedCrossRefGoogle Scholar
  191. Thomas ED (1999) A history of haemopoietic cell transplantation. Br J Haematol 105:330–339PubMedCrossRefGoogle Scholar
  192. Thomas ED, Lochte HL Jr, Lu WC, Ferrebee JW (1957) Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med 257:491–496.  https://doi.org/10.1056/NEJM195709122571102 PubMedCrossRefGoogle Scholar
  193. To LB et al (2003) Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim. Bone Marrow Transplant 31:371–378.  https://doi.org/10.1038/sj.bmt.1703860 PubMedCrossRefGoogle Scholar
  194. Tortorella C, Simone O, Piazzolla G, Stella I, Antonaci S (2007) Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. Ageing Res Rev 6:81–93PubMedCrossRefGoogle Scholar
  195. Toubert A (2012) Immune reconstitution after allogeneic HSCT. In: Apperley J, Carreras E, Gluckman E, Massszi T (eds) The EBMT handbook 6th edition. Haemopoietic stem cell transplantation. ESH & EBMTGoogle Scholar
  196. Trzonkowski P, Myśliwska J, Szmit E, Wickiewicz J, Łukaszuk K, Brydak LB, Machała M, Myśliwski A (2003) Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination—an impact of immunosenescence. Vaccine 21:3826–3836PubMedCrossRefGoogle Scholar
  197. Ventevogel MS, Sempowski GD (2013) Thymic rejuvenation and aging. CurrOpinImmunol 25:516–522Google Scholar
  198. Verovskaya E, Broekhuis MJ, Zwart E, Ritsema M, van Os R, de Haan G, Bystrykh LV (2013) Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding. Blood 122:523–532.  https://doi.org/10.1182/blood-2013-01-481135 PubMedCrossRefGoogle Scholar
  199. Wahlestedt M, Bryder D (2017) The slippery slope of hematopoietic stem cell aging. Exp Hematol 56:1–6.  https://doi.org/10.1016/j.exphem.2017.1009.1008
  200. Wahlestedt M, Pronk CJ, Bryder D (2015) Concise review: hematopoietic stem cell aging and the prospects for rejuvenation. Stem Cells Transl Med 4(2):186–194.  https://doi.org/10.5966/sctm.2014-0132
  201. Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS (1990) Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol 45:M45–M48PubMedCrossRefGoogle Scholar
  202. Weinberger B, Herndler-Brandstetter D, Schwanninger A, Weiskopf D, Grubeck-Loebenstein B (2008) Biology of immune responses to vaccines in elderly persons. Clin Infect Dis 46:1078–1084PubMedCrossRefGoogle Scholar
  203. Weinert BT, Timiras PS (2003) Invited review: theories of aging. J Appl Physiol 95:1706–1716PubMedCrossRefGoogle Scholar
  204. Weksler ME (2000) Changes in the B-cell repertoire with age. Vaccine 18:1624–1628PubMedCrossRefGoogle Scholar
  205. Weng NP, Akbar AN, Goronzy J (2009) CD28(-) T cells: their role in the age-associated decline of immune function. Trends Immunol 30:306–312PubMedPubMedCentralCrossRefGoogle Scholar
  206. Wenisch C, Patruta S, Daxbîck F, Krause R, Hîrl W (2000) Effect of age on human neutrophil function. J Leukoc Biol 67:40–45PubMedCrossRefGoogle Scholar
  207. Westin ER, Chavez E, Lee KM, Gourronc FA, Riley S, Lansdorp PM, Goldman FD, Klingelhutz AJ (2007) Telomere restoration and extension of proliferative lifespan in dyskeratosis congenita fibroblasts. Aging Cell 6:383–394.  https://doi.org/10.1111/j.1474-9726.2007.00288.x PubMedPubMedCentralCrossRefGoogle Scholar
  208. Winkler IG, Levesque JP (2006) Mechanisms of hematopoietic stem cell mobilization: when innate immunity assails the cells that make blood and bone. Exp Hematol 34:996–1009.  https://doi.org/10.1016/j.exphem.2006.04.005 PubMedCrossRefGoogle Scholar
  209. Wong C, Goldstein DR (2013) Impact of aging on antigen presentation cell function of dendritic cells. Curr Opin Immunol 25:535–541.  https://doi.org/10.1016/j.coi.2013.05.016 PubMedPubMedCentralCrossRefGoogle Scholar
  210. Woollard KJ (2013) Immunological aspects of atherosclerosis. Clin Sci 125:221–235PubMedCrossRefGoogle Scholar
  211. Woolthuis CM, Mariani N, Verkaik-Schakel RN, Brouwers-Vos AZ, Schuringa JJ, Vellenga E, de Wolf JTM, Huls G (2014) Aging impairs long-term hematopoietic regeneration after autologous stem cell transplantation. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 20:865–871.  https://doi.org/10.1016/j.bbmt.2014.03.001 CrossRefGoogle Scholar
  212. Yang Y, Li T, Nielsen ME (2012) Aging and cancer mortality: dynamics of change and sex differences. Exp Gerontol 47:695–705.  https://doi.org/10.1016/j.exger.2012.06.009 PubMedPubMedCentralCrossRefGoogle Scholar
  213. Yu BP, Chung HY (2001) Oxidative stress and vascular aging. Diabetes Res Clin Pract 54(Suppl 2):S73–S80PubMedCrossRefGoogle Scholar
  214. Yun J, Finkel T (2014) Mitohormesis. Cell Metab 19:757–766.  https://doi.org/10.1016/j.cmet.2014.01.011 PubMedPubMedCentralCrossRefGoogle Scholar
  215. Zheng B, Han S, Takahashi Y, Kelsoe G (1997) Immunosenescence and germinal center reaction. Immunol Rev 160:63–77PubMedCrossRefGoogle Scholar
  216. Zou Y, Jung KJ, Kim JW, Yu BP, Chung HY (2004) Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction. FASEB J 18:320–322PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2018

Authors and Affiliations

  1. 1.Blood Transfusion Centre of SloveniaLjubljanaSlovenia

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