Top

Published in:

Open Access 01-12-2018 | Review

Interventions to restore appropriate immune function in the elderly

Authors: Richard Aspinall, Pierre Olivier Lang

Published in: Immunity & Ageing | Issue 1/2018

Abstract

Advanced age is one indicator of likely immune dysfunction. As worldwide, the global population contains progressively more and more older individuals there is likelihood of an increased prevalence and incidence of infectious diseases due to common and emergent pathogens. The resultant increase in mortality and morbidity would be matched by the risk of functional decline and disability. Maintaining immune function at a plateau throughout life may therefore be associated with considerable cost savings. The aim of improving immune function in older individuals may be achieved through considering a therapeutic approach to rejuvenate, stimulate or support the indigenous immune system to perform in a more optimal manner. In terms of cost effectiveness a therapeutic approach may prove difficult because of issues associated with; identifying those who would benefit the most from this treatment, identifying the type of treatment which would suit them and identifying whether the treatment was successful. The alternative of supporting or providing a stronger stimulus through vaccination, whilst more cost effective, may be a more valuable option in the short term. Both approaches will be addressed in this review.

Fulop T, et al. Aging, frailty and age-related diseases. Biogerontology. 2010;11:547–63. https://doi.org/10.1007/s10522-010-9287-2.CrossRefPubMed

Lang PO, Mitchell WA, Lapenna A, Pitts D, Aspinall R. Immunological pathogenesis of main aged-related disease and frailty: role of immunosenescence. Eur Geriatric Med. 2010;1:9.CrossRef

Cliff A, Haggett P. Time, travel and infection. Br Med Bull. 2004;69:87–99. https://doi.org/10.1093/bmb/ldh011.CrossRefPubMed

Lang, P. O., Loulergue, P. & Aspinall, R. Chikungunya Virus Infection: Why Should U.S. Geriatricians Be Aware of It? J Am Geriatr Soc. 2017. https://doi.org/10.1111/jgs.15104.

Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2017; https://doi.org/10.1111/resp.13196.

Aspinall R, Lang PO. Vaccination choices for older people, looking beyond age specific approaches. Expert Rev Vaccines. 2018;17:23-30. https://doi.org/10.1080/14760584.2018.1411197.

Lang PO, Trivalle C, Vogel T, Proust J, Papazian JP. Markers of metabolic and cardiovascular health in adults: comparative analysis of DEXA-based body composition components and BMI categories. J Cardiol. 2015;65:42–9. https://doi.org/10.1016/j.jjcc.2014.03.010.CrossRefPubMed

Lang PO, et al. Is obesity a marker of robustness in vulnerable hospitalized aged populations? Prospective, multicenter cohort study of 1 306 acutely ill patients. J Nutr Health Aging. 2014;18:66–74. https://doi.org/10.1007/s12603-013-0352-9.CrossRefPubMed

Dixit VD. Thymic fatness and approaches to enhance thymopoietic fitness in aging. Curr Opin Immunol. 2010;22:521–8. https://doi.org/10.1016/j.coi.2010.06.010.CrossRefPubMedCentralPubMed

10.

Yang H, et al. Obesity accelerates thymic aging. Blood. 2009;114:3803–12. https://doi.org/10.1182/blood-2009-03-213595.CrossRefPubMedCentralPubMed

11.

Yang H, Youm YH, Dixit VD. Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution. J Immunol. 2009;183:3040–52. https://doi.org/10.4049/jimmunol.0900562.CrossRefPubMedCentralPubMed

12.

Siegrist CA, Aspinall R. B-cell responses to vaccination at the extremes of age. Nat Rev Immunol. 2009;9:185–94. https://doi.org/10.1038/nri2508.CrossRefPubMed

13.

Bharath LP, Ip BC, Nikolajczyk BS. Adaptive immunity and metabolic health: harmony becomes dissonant in obesity and aging. Compr Physiol. 2017;7:1307–37. https://doi.org/10.1002/cphy.c160042.CrossRefPubMed

14.

Choi CHJ, Cohen P. Adipose crosstalk with other cell types in health and disease. Exp Cell Res. 2017;360:6–11. https://doi.org/10.1016/j.yexcr.2017.04.022.CrossRefPubMed

15.

Calder PC, et al. Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res Rev. 2017;40:95–119. https://doi.org/10.1016/j.arr.2017.09.001.CrossRefPubMed

16.

Johnson MO, Siska PJ, Contreras DC, Rathmell JC. Nutrients and the microenvironment to feed a T cell army. Semin Immunol. 2016;28:505–13. https://doi.org/10.1016/j.smim.2016.09.003.CrossRefPubMedCentralPubMed

17.

Seman K, Abdul Manaf H, Ismail AR. Association between functional dentition with inadequate calorie intake and underweight in elderly people living in “Pondok” in Kelantan. Arch Orofac Sci. 2007;2(1):10-9.

18.

Langkamp-Henken B, et al. Nutritional formula improved immune profiles of seniors living in nursing homes. J Am Geriatr Soc. 2006;54:1861–70. https://doi.org/10.1111/j.1532-5415.2006.00982.x.CrossRefPubMed

19.

Akatsu H, et al. Enhanced vaccination effect against influenza by prebiotics in elderly patients receiving enteral nutrition. Geriatr Gerontol Int. 2016;16:205–13. https://doi.org/10.1111/ggi.12454.CrossRefPubMed

20.

Vidal K, et al. Immunomodulatory effects of dietary supplementation with a milk-based wolfberry formulation in healthy elderly: a randomized, double-blind, placebo-controlled trial. Rejuvenation Res. 2012;15:89–97. https://doi.org/10.1089/rej.2011.1241.CrossRefPubMed

21.

Girodon F, et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN VIT AOX Geriatr Netw Arch Intern Med. 1999;159:748–54.CrossRef

22.

Freeman SL, et al. Dairy proteins and the response to pneumovax in senior citizens: a randomized, double-blind, placebo-controlled pilot study. Ann N Y Acad Sci. 2010;1190:97–103. https://doi.org/10.1111/j.1749-6632.2009.05264.x.CrossRefPubMed

23.

Moriguti JC, Ferriolli E, Donadi EA, Marchini JS. Effects of arginine supplementation on the humoral and innate immune response of older people. Eur J Clin Nutr. 2005;59:1362–6. https://doi.org/10.1038/sj.ejcn.1602247.CrossRefPubMed

24.

Pae M, Meydani SN, Wu D. The role of nutrition in enhancing immunity in aging. Aging Dis. 2012;3:91–129.PubMed

25.

Braga CB, et al. Effect of zinc supplementation on serological response to vaccination against streptococcus Pneumoniae in patients undergoing chemotherapy for colorectal cancer. Nutr Cancer. 2015;67:926–32. https://doi.org/10.1080/01635581.2015.1053497.CrossRefPubMed

26.

Lang PO, Aspinall R. Vitamin D status and the host resistance to infections: what it is currently (not) understood. Clin Ther. 2017;39:930–45. https://doi.org/10.1016/j.clinthera.2017.04.004.CrossRefPubMed

27.

Keating R, et al. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol. 2013;14:1266–76. https://doi.org/10.1038/ni.2741.CrossRefPubMedCentralPubMed

28.

Mannick, J. B. et al. mTOR inhibition improves immune function in the elderly. Science translational medicine 6, 268ra179, https://doi.org/10.1126/scitranslmed.3009892 (2014).

29.

Lefebvre JS, Haynes L. Vaccine strategies to enhance immune responses in the aged. Curr Opin Immunol. 2013;25:523–8. https://doi.org/10.1016/j.coi.2013.05.014.CrossRefPubMedCentralPubMed

30.

Cunningham AL, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375:1019–32. https://doi.org/10.1056/NEJMoa1603800.CrossRefPubMed

31.

Levin MJ. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr Opin Immunol. 2012;24:494–500. https://doi.org/10.1016/j.coi.2012.06.002.CrossRefPubMed

32.

Stowe RP, et al. Chronic herpesvirus reactivation occurs in aging. Exp Gerontol. 2007;42:563–70. https://doi.org/10.1016/j.exger.2007.01.005.CrossRefPubMedCentralPubMed

33.

Cobbold M, et al. Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med. 2005;202:379–86. https://doi.org/10.1084/jem.20040613.CrossRefPubMedCentralPubMed

34.

Neuenhahn, M. et al. Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 31, 2161-2171, https://doi.org/10.1038/leu.2017.16 (2017).

35.

Dave H, et al. Toward a rapid production of multivirus-specific T cells targeting BKV, adenovirus, CMV, and EBV from umbilical cord blood. Mol Ther Methods Clin Dev. 2017;5:13–21. https://doi.org/10.1016/j.omtm.2017.02.001.CrossRefPubMedCentralPubMed

36.

Loffredo FS, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013;153:828–39. https://doi.org/10.1016/j.cell.2013.04.015.CrossRefPubMedCentralPubMed

37.

Villeda SA, et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014;20:659–63. https://doi.org/10.1038/nm.3569.CrossRefPubMedCentralPubMed

38.

Davies J, Pulko V, Thompson H, Nikolich-Zugich J. Hetero.Chronic parabiosis: allowing the dissection of the aged immune system. J Immunol. 2015;194:1.CrossRef

39.

Pishel I, et al. Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis. Rejuvenation Res. 2012;15:239–48. https://doi.org/10.1089/rej.2012.1331.CrossRefPubMed

40.

Huestis D, Alexander W. Bogdanov: the forgotten pioneer of blood transfusion. Transfus Med Rev. 2007;21:337–40. https://doi.org/10.1016/j.tmrv.2007.05.008.CrossRefPubMed

41.

Aspinall R, Govind S, Lapenna A, Lang PO. Dose response kinetics of CD8 lymphocytes from young animals transfused into old animals and challenged with influenza. Immun Ageing : I & A. 2013;10:34. https://doi.org/10.1186/1742-4933-10-34.CrossRef

42.

Mackall CL, Fry TJ, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol. 2011;11:330–42. https://doi.org/10.1038/nri2970.CrossRefPubMed

43.

Andrew D, Aspinall R. Il-7 and not stem cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice. J Immunol. 2001;166:1524–30.CrossRefPubMed

44.

Muegge K, Vila MP, Durum SK. Interleukin-7: a cofactor for V(D)J rearrangement of the T cell receptor beta gene. Science. 1993;261:93–5.CrossRefPubMed

45.

Lundstrom W, Fewkes NM, Mackall CL. IL-7 in human health and disease. Semin Immunol. 2012;24:218–24. https://doi.org/10.1016/j.smim.2012.02.005.CrossRefPubMedCentralPubMed

46.

Fry TJ, Mackall CL. The many faces of IL-7: from lymphopoiesis to peripheral T cell maintenance. J Immunol. 2005;174:6571–6.CrossRefPubMed

47.

Bhatia SK, Tygrett LT, Grabstein KH, Waldschmidt TJ. The effect of in vivo IL-7 deprivation on T cell maturation. J Exp Med. 1995;181:1399–409.CrossRefPubMed

48.

Henson SM, Snelgrove R, Hussell T, Wells DJ, Aspinall R. An IL-7 fusion protein that shows increased thymopoietic ability. J Immunol. 2005;175:4112–8.CrossRefPubMed

49.

El Kassar N, et al. A dose effect of IL-7 on thymocyte development. Blood. 2004;104:1419–27. https://doi.org/10.1182/blood-2004-01-0201.CrossRefPubMed

50.

El-Kassar N, et al. High levels of IL-7 cause dysregulation of thymocyte development. Int Immunol. 2012;24:661–71. https://doi.org/10.1093/intimm/dxs067.CrossRefPubMedCentralPubMed

51.

Aspinall R, et al. Old rhesus macaques treated with interleukin-7 show increased TREC levels and respond well to influenza vaccination. Rejuvenation Res. 2007;10:5–17. https://doi.org/10.1089/rej.2006.9098.CrossRefPubMed

52.

Rosenberg SA, et al. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006;29:313–9. https://doi.org/10.1097/01.cji.0000210386.55951.c2.CrossRefPubMedCentralPubMed

53.

Tredan O, et al. ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4+ lymphocyte count in lymphopenic metastatic breast cancer patients. Ann Oncol. 2015;26:1353–62. https://doi.org/10.1093/annonc/mdv173.CrossRefPubMed

54.

Goldberg GL, et al. Sex steroid ablation enhances lymphoid recovery following autologous hematopoietic stem cell transplantation. Transplantation. 2005;80:1604–13.CrossRefPubMed

55.

Heng TS, et al. Effects of castration on thymocyte development in two different models of thymic involution. J Immunol. 2005;175:2982–93.CrossRefPubMed

56.

Min H, Montecino-Rodriguez E, Dorshkind K. Reassessing the role of growth hormone and sex steroids in thymic involution. Clin Immunol. 2006;118:117–23. https://doi.org/10.1016/j.clim.2005.08.015.CrossRefPubMed

57.

Greenstein BD, Fitzpatrick FT, Kendall MD, Wheeler MJ. Regeneration of the thymus in old male rats treated with a stable analogue of LHRH. J Endocrinol. 1987;112:345–50.CrossRefPubMed

58.

Scalea JR, et al. The rejuvenating effects of leuprolide acetate on the aged baboon's thymus. Transpl Immunol. 2014;31:134–9. https://doi.org/10.1016/j.trim.2014.09.001.CrossRefPubMedCentralPubMed

59.

Velardi E, et al. Sex steroid blockade enhances thymopoiesis by modulating notch signaling. J Exp Med. 2014;211:2341–9. https://doi.org/10.1084/jem.20131289.CrossRefPubMedCentralPubMed

60.

Velardi E, Dudakov JA, van den Brink MR. Sex steroid ablation: an immunoregenerative strategy for immunocompromised patients. Bone Marrow Transplant. 2015;50(Suppl 2):S77–81. https://doi.org/10.1038/bmt.2015.101.CrossRefPubMedCentralPubMed

61.

Sutherland JS, et al. Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol. 2005;175:2741–53.CrossRefPubMed

62.

Ornitz DM, Itoh N. Fibroblast growth factors. Genome Biol. 2001;2(3):REVIEWS3005. Epub 2001 Mar 9.

63.

Berzins SP, et al. Thymic regeneration: teaching an old immune system new tricks. Trends Mol Med. 2002;8:469–76.CrossRefPubMed

64.

Min D, et al. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007;109:2529–37. https://doi.org/10.1182/blood-2006-08-043794.CrossRefPubMedCentralPubMed

65.

Seggewiss R, et al. Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood. 2007;110:441–9. https://doi.org/10.1182/blood-2006-12-065623.CrossRefPubMedCentralPubMed

66.

Jacobson JM, et al. A randomized controlled trial of palifermin (recombinant human keratinocyte growth factor) for the treatment of inadequate CD4+ T-lymphocyte recovery in patients with HIV-1 infection on antiretroviral therapy. J Acquir Immune Defic Syndr. 2014;66:399–406. https://doi.org/10.1097/QAI.0000000000000195.CrossRefPubMedCentralPubMed

67.

Benetos A, et al. Polypharmacy in the aging patient: Management of Hypertension in octogenarians. JAMA. 2015;314:170–80. https://doi.org/10.1001/jama.2015.7517.CrossRefPubMed

68.

Lang PO, Govind S, Aspinall R. Reversing T cell immunosenescence: why, who, and how. Age. 2013;35:609–20. https://doi.org/10.1007/s11357-012-9393-y.CrossRefPubMed

69.

Lang PO, et al. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence. Clin Interv Aging. 2012;7:55–64. https://doi.org/10.2147/CIA.S25215.CrossRefPubMedCentralPubMed

70.

Pica N, et al. Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. Proc Natl Acad Sci U S A. 2012;109:2573–8. https://doi.org/10.1073/pnas.1200039109.CrossRefPubMedCentralPubMed

71.

Lang PO, Bonduelle O, Benhabiles N, Combadiere B. Prior contact with the 2000-2003 seasonal vaccines extends the 2009 pandei a/H1N1 vaccine specific immune protection to non-numoral compartments. Eur Geriatric Med. 2014;5:2.CrossRef

72.

Musher DM, et al. Safety and antibody response, including antibody persistence for 5 years, after primary vaccination or revaccination with pneumococcal polysaccharide vaccine in middle-aged and older adults. J Infect Dis. 2010;201:516–24. https://doi.org/10.1086/649839.CrossRefPubMed

73.

Percival SS. Aged garlic extract modifies human immunity. J Nutr. 2016;146:433S–6S. https://doi.org/10.3945/jn.115.210427.CrossRefPubMed

74.

Moro-Garcia MA, et al. Oral supplementation with lactobacillus delbrueckii subsp. bulgaricus 8481 enhances systemic immunity in elderly subjects. Age. 2013;35:1311–26. https://doi.org/10.1007/s11357-012-9434-6.CrossRefPubMed

75.

Akbar AN, et al. Investigation of the cutaneous response to recall antigen in humans in vivo. Clin Exp Immunol. 2013;173:163–72. https://doi.org/10.1111/cei.12107.CrossRefPubMedCentralPubMed

76.

Ndumbi P, Gilbert L, Tsoukas CM. Comprehensive evaluation of the immune risk phenotype in successfully treated HIV-infected individuals. PLoS One. 2015;10:e0117039. https://doi.org/10.1371/journal.pone.0117039.CrossRefPubMedCentralPubMed

77.

Pera A, et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015;82:50–5. https://doi.org/10.1016/j.maturitas.2015.05.004.CrossRefPubMed

Title: Interventions to restore appropriate immune function in the elderly
Authors: Richard Aspinall
Pierre Olivier Lang
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Immunity & Ageing / Issue 1/2018
Electronic ISSN: 1742-4933
DOI: https://doi.org/10.1186/s12979-017-0111-6

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Interventions to restore appropriate immune function in the elderly

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications

Correction to: Virtual memory cells make a major contribution to the response of aged influenza-naïve mice to influenza virus infection

A comprehensive characterization of aggravated aging-related changes in T lymphocytes and monocytes in end-stage renal disease: the iESRD study

The association of high sensitivity C-reactive protein and incident Alzheimer disease in patients 60 years and older: The HUNT study, Norway

The baseline levels and risk factors for high-sensitive C-reactive protein in Chinese healthy population

CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page