Abstract
Senescence is an irreversible process by which cells enter to a permanent cell cycle arrest with generalized molecular changes. Senescent cells remain metabolically active and most of them show a secretory phenotype; through its secretion may induce senescence or cancer in other cells. The secretory cells in the so-called transient senescence may participate in embryogenesis, tissue regeneration and immune response. The deleterious changes associated with age affect the immune system members and the immune senescence cause poor response to vaccines and susceptibility to cancer and infections. These latter are a frequent cause of asthma mostly in the elderly, the incidence is increasing in old people, and it may be related with those anatomical, physiological and immune changes caused by age, asthma chronicity and external agents. Comorbidity in the elderly worsens the ailment and hinders diagnosis, therefore, knowledge and handling of these clinical entities must be in control by the physicians responsible of the first level attention to old patients.
References
Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, et al. INK4a/Arf expression is a biomarker of aging. J Clin Invest. 2004;114(9):1299-1307. DOI: http://dx.doi.org/10.1172/JCI22475
Deursen I. The role of senescent cells in ageing. Nature. 2014;509(7501):439-446. DOI: http://dx.doi.org/10.1038/nature13193
Prokocimer M, Barkan R. Gruenbaum Y. Hutchinson-Gilford progeria syndrome through the lens of transcription. Aging Cell. 2013;12(4):533-543. DOI: http://dx.doi.org/10.1111/acel.12070
Swajari V, Nakamura A. Speeding up the clock. The past, present and future of progeria. Dev Growth Differ. 2016;58(1):116-130. DOI: http://dx.doi.org/10.1111/dgd.12251
Oliveira BF, Nogueira-Machado JA, Chaves MM. The role of oxidative stress in the aging process. ScientificWorldJournal. 2010;10:1121-1128. DOI: http://dx.doi.org/10.1100/tsw.2010.94
Williams GC. Pleiotroy, natural selection, and the evolution of senescence. Evolution. 1957;11(4):398-411. DOI: http://dx.doi.org/10.2307/2406060
Opesko P, Shay J. Telomere-associated aging disorders. Aging Res Rev. 2017;33:52-66. DOI: http://dx.doi.org/10.1016/j.arr.2016.05.009
Greider CW. Molecular biology Wnt regulates TERT-putting the horse before the cart. Science. 2012;336(6088):1519-1520. DOI: http://dx.doi.org/10.1126/science.1223785
Akincilar S, Unal B, Tergaonkar V. Reactivation of telomerase in cancer. Cell Mol Life Sci. 2016;73(8):1659-1670. DOI: http://dx.doi.org/10.1007/s00018-016-2146-9
Lin Y, Uemura H, Fujinami K, Hosaka M, Harada M, Kubota Y. Telomerase activity in primary prostate cancer. J Urol. 1997;157(3):1161-1165. DOI: http://dx.doi.org/10.1016/S0022-5347(01)65160-7
Choi J, Fauce SR, Effros RB. Reduced telomerase activity in human T lymphocytes exposed to cortisol. Brain Behav Immun. 2008;22(4):600-605. DOI: http://dx.doi.org/10.1016/j.bbi.2007.12.004
Weng NP, Hathcock KS, Hode RJ. Regulation of telomere length and telomerase in T and B cells a mechanism for maintaining replicative potential. Immunity. 1998;9(2):151-157. DOI: http://dx.doi.org/10.1016/S1074-7613(00)80597-X
Norrback K, Dahlenborg K, Carlsson R, Roos G. Telomerase activation in normal B lymphocytes and non-Hodgkin’s lymphomas. Blood. 1996;88(1):222-229. Disponible en: http://www.bloodjournal.org/content/88/1/222
Davalos AR, Coppé JP, Campisi J, Desprez PY. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev. 2010;29(2):273-283. DOI: http://dx.doi.org/10.1007/s10555-010-9220-9
Rodier F. Detection of the senescence-associated secretory phenotype (SASP). Methods Mol Biol. 2013;96:165-173.
Ohtani N, Hara E. Roles and mechanisms of cellular senescence in regulation of tissue. Cancer Sci. 2013;104(5):525-530. DOI: http://dx.doi.org/10.1111/cas.12118
Adams PD, Sedivy JM. Cellular senescence and tumor suppression. London: Springer; 2010.
Kulman T, Peeper DS. Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer. 2009;9(2):81-94. DOI: http://dx.doi.org/10.1038/nrc2560
Coppé JP, Patil CK, Rodier F, Krtolica A, Beauséjour CM, Parrinello S, et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE. 2010;5(2):e9188. DOI: http://dx.doi.org/10.1371/journal.pone.0009188
Campisi J. Aging, cellular senescence and cancer. Annu Rev Physiol. 2013;75;685-705. DOI: http://dx.doi.org/10.1146/annurev-physiol-030212-183653
Muñoz-Espin D, Canamaro M, Marauer A, Gómez-López G, Contreras J, Murillo-Cuesta S, et al. Programmed cell senescence during mammalian embryonic development. Cell. 2013;155(5):1104-1118. DOI: http://dx.doi.org/10.1016/j.cell.2013.10.019
Chou P, Effros RB. T cell replicative senescence in human aging. Curr Pharm Des. 2013;19(9):1680-1698. DOI: http://dx.doi.org/10.2174/1381612811319090016
Rajapopalan S, Lee E, DuPrie M, Long EO. TNFR-associated factor 6 and TGFβ activated kinase 1 control signals for a senescence response by an endosomal NK receptor. J Immunol. 20014;192(2):714-721. DOI: http://dx.doi.org/10.4049/jimmunol.1302384
Ye J, Huang X, Hsueh E, Zhang Q, Ma C, Zhang Y, et al. Human regulatory T cells induce T-lymphocyte senescence. Blood. 2012;120(10):2021-2031. DOI: http://dx.doi.org/10.1182/blood-2012-03-416040
Jun JI, Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol. 2010;12(7):676-685. DOI: http://dx.doi.org/10.1038/ncb2070
Heffner KL. Neuroendocrine effects of stress on immunity in the elderly: implications for inflammatory disease. Immunol Allergy Clin North Am. 2011;31(1):95-108. DOI: http://dx.doi.org/10.1016/j.iac.2010.09.005
Fülöp T Jr, Fouquet C, Allaire P, Perrin N, Lacombe G, Stankova J, et al. Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev. 1997; 96(1-3):15-34.
Corberand J, Ngyen F, Laharrague P, Fontanilles AM, Gleyzes B, Gyrard E, et al. Polymorphonuclear functions and aging in humans. J Am Geriatr Soc. 1981;29(9):391-397. DOI: http://dx.doi.org/10.1111/j.1532-5415.1981.tb02376.x
Plowden J, Renshaw-Hoelscher M, Panda A, Katz K, Sambhara E. Innate immunity in aging impact on macrophage function. Aging Cell. 2004;3(4):161-167.
Fülöp T Jr, Fons G, Worum I, Paragh G, Leövey A. Age related variations of some polymorphonuclear leukocyte functions. Mech Ageing Dev. 1985;19:1-8. DOI: http://dx.doi.org/10.1111/j.1474-9728.2004.00102.x
van-Duin D, Allore H, Mohanty S, Ginter S, Newman FK, Belshe RB, et al. Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. J Infect Dis. 2007;195(11):1590-1597. DOI: https://doi.org/10.1086/516788
Agrawal A, Agrawal S, Gupta S. Dendritic cells in human aging. Exp Gerontol. 2007;42(5):421-426. doi: 10.1016/j.exger.2006.11.007
Chuang SY, Lin Ch, Fang JY. Natural compounds and aging: between autophagy and inflammasome. Biomed Res Int. 2014; 10 pages. DOI: http://dx.doi.org/10.1155/2014/297293
Nyugen J, Agrawal S, Gollapudi S, Gupta S. Impaired function of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol. 2010;30(6):806-813. DOI: http://dx.doi.org/10.1007/s10875-010-9448-8
Hazeldine J, Lord J. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013;12(4):1069-1078. DOI: http://dx.doi.org/10.1016/j.arr.2013.04.00336.
Iannello A, Thompson TW, Ardolino M, Lowe SW, Raulet DH. P-53 dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. J Exp Med. 213;210(10):2057-2069. DOI: http://dx.doi.org/10.1084/jem.2013078337.
Iannello A, Raulet DH. Immunosurveillance of senescent cancer cells by natural killer cells. Oncoimmunology. 2014;3:e27616. DOI: http://dx.doi.org/10.4161/onci.27616
De-la-Rosa O, Tarazona R, Casado JG, Alonso C, Belén Ostos, Peña J, et al. Vα24(+) NKT cells are decreased in elderly humans. Exp Gerontol. 2002;37:213-217. DOI: https://doi.org/10.1016/S0531-5565(01)00186-3
Mahbub S, Brubaker A, Kovaks EJ. Aging of the innate immune system an update. Curr Imunol Rev. 2011;7(1):104-115. DOI: http://dx.doi.org/10.2174/157339511794474181
Salminen A, Kauppinen A, Kaarnironta K. Emerging role of NFkB signaling in the induction of the senescence-associated secretory phenotype (SASP). Cell Signal. 2012;24(4):835-845. DOI: http://dx.doi.org/10.1016/j.cellsig.2011.12.006
Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, et al. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA-4. Science. 2015;349(6255):aaa5612. DOI: http://dx.doi.org/10.1126/science.aaa5612
Fitzpatrick AL, Kronmal RA, Gardner JP, Psaty BM, Jenny NS, Tracy RP, et al. Leukocyte telomere length and cardiovascular diseases in the cardiovascular health study. Am J Epidemiol. 2007;165(1):14-21. DOI: http://dx.doi.org/10.1093/aje/kwj346
Lang S, Xue Q, Tian J, Walston JD, Fried LP. Inflammation and fraility in older woman. J Am Geriatr Soc. 2007;55(6):864-871. DOI: http://dx.doi.org/10.1111/j.1532-5415.2007.01186.x
Gruver AL, Hudson LL, Sempowsky GD. Imunosenescence of ageing. J Pathol. 2007;211(2):144-156. DOI: 10.1002/path.2104
Savino W. Neuroendocrine control of T cell development in mammals role of growth hormone in modulating thymocyte migration. Exp Physiol. 2007;92(5):813-817. DOI: http://dx.doi.org/10.1113/expphysiol.2007.038422
Mackall C, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is imited in diversity and prone to skewing. J Immunol. 1996;156(12):4609-4616.
Effros RB. Replicative senescence of CD8T cells: Effect on human ageing. Exp Gerontol. 2004;39(4):517-524. DOI: http://dx.doi.org/10.1016/j.exger.2003.09.024
Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, et al. The influence of age on T cell generation and TCR diversity. J Immunol 2005;174(119:7446-7452.
Weng N, Akbar A, Goronzy J. CD28- T cells: their role in the age-associated decline of immune function. Trends Immunol. 2009;30(7):306-312. DOI: http://dx.doi.org/10.1016/j.it.2009.03.013
Fullop T, Le Page A, Fortin C, Witkowski JM, Dupuis G, Larbi A. Cellular signaling in the aging immune system. Curr Opin Immunol. 2014;29:105-111. DOI: http://dx.doi.org/10.1016/j.coi.2014.05.007
Effross RB, Dagarag M, Spaulding C, Man J. The role of CD8+ T cell replicative senescence in human aging. Immunol Rev. 2005;205:147-157. DOI: http://dx.doi.org/10.1111/j.0105-2896.2005.00259.x
Simone R, Zicca A, Saverino D. The frequency of regulatory CD3+, CD8+, CD28-, CD25+ T lymphocytes in human peripheral blood increases with age. J Leukoc Biol. 2008;84(6):1454-1461. DOI: http://dx.doi.org/10.1189/jlb.0907627
Lages CS, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, et al. Functional regulatory T cells accumulate in aged host and promote chronic infectious disease reactivation. J Immunol. 2008;181(3):1835-1848. DOI: https://doi.org/10.4049/jimmunol.181.3.1835
Jagger A, Shimojima Y, Goronzy JJ, Weyand CM. Regulatory T cells and the immune aging process: a mini-review. Gerontology. 2014;60(2):130-137. DOI: http://dx.doi.org/10.1159/000355303
Gark SK, Delaney C, Toubai T, Ghosh A, Reddy P, Banerjee R, et al. Aging is associated with increased regulatory T-cell function. Aging Cell. 2014;13(3):441-448. DOI: http://dx.doi.org/10.1111/acel.12191.
Herman A, List C, Habisch HJ, Vukicevic V, Ehrhart-Bornstein M, Brenner R. Age-dependent neuroectodermal differentiation capacity of human mesenchymal stromal cells: limitations for autologous cell replacement strategies. Cytotherapy. 2010;12(1):17-30. DOI: http://dx.doi.org/10.3109/14653240903313941
Cho RH, Sieburg HB, Muller-Sieburg CE. 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. 2008;111(12):5553-5561. DOI: http://dx.doi.org/10.1182/blood-2007-11-123547
Pang WW, Price EA, Sahoo D, Beerman I, Maloney WJ, Rossi DJ, et al. Human bone marrow hematopoietic stem cell are increased in frequency and myeloid-based with age. Proc Natl Acad Sci USA. 211;108(50):2012-2017. DOI: http://dx.doi.org/10.1073/pnas.1116110108
Lichtman M, Rowe J. The relationship of patient age to the pathobiology of the clonal myeloid diseases. Semin Oncol. 2004;31(2):185-197. DOI: http://dx.doi.org/10.1053/j.seminoncol.2003.12.029
van-Deursen J. The role of senescent cells in ageing. Nature. 2014;509(7501):439-446. DOI: http://dx.doi.org/10.1038/nature13193
Weiskoff D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009;22(11):1041-1050. DOI: http://dx.doi.org/10.1111/j.1432-2277.2009.00927.x
Frasca D. Blomberg BB. Aging affects human B cell responses. J Clin Immunol. 2011;31(3):430-435. DOI: http://dx.doi.org/10.1007/s10875-010-9501-7
Buffa S, Bulati M, Pellicano M, Dunn-Walters DK, Wu YC, Candore G, et al. B cell immunosenescence: different features of naive and memory B cell in elderly. Biogerontology. 2011;12(5):473-483. DOI: http://dx.doi.org/10.1007/s10522-011-9353-4
Bartek J, Hodny Z, Lukas J. Cytokine loops driving senescence. Nat Cell Biol. 2008;10(8):887-889. DOI: http://dx.doi.org/10.1038/ncb0808-887
Kuilman T, Michaloglou Ch, Vredeveld L, Douma S, van-Doorn R, Desmet CJ, et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell. 2008;133(6):1019-1031. DOI: http://dx.doi.org/10.1016/j.cell.2008.03.039
Fernández-Morera J, Calvanese V, Rodríguez-Rodere S, Menéndez-Torre E, Fraga MF. Epigenetic regulation of the immune system in health and disease. Tissue Antigens. 2010;76(6):431-439. DOI: http://dx.doi.org/10.1111/j.1399-0039.2010.01587.x
Rink L, Cakmann I, Kirchner H. Altered cytokine production in the elderly. Mech Ageing Dev. 1998;102(2-3):199-209.
Ongrády J, Kövesdi V. Factors that may impact on immunosenescence: an appraisal. Immun Ageing. 2010;7:7. DOI: http://dx.doi.org/10.1186/1742-4933-7-7.
Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis. 2000;182 Suppl 1:S62-S68. DOI: 10.1086/315916
Ibs KH, Rink L. Zinc-altered immune function. J Nutr. 2003;133(5 Suppl 1):1452S-1452S.
Mathur S. Allergy and asthma in the ederly. Sem Resp Crit Care Med. 2010;31(5):587-595. DOI: http://dx.doi.org/10.1055/s-0030-1265899
Tsai C, Lee W, Hanania N, Camargo CA Jr. Age-related differences in clinical outcomes for acute asthma in the United States, 2006-2008. J Allergy Clin Immunol. 2012;129(5):1252-1258.e1. DOI: http://dx.doi.org/10.1016/j.jaci.2012.01.061
Meyer K, Rosenthal N, Soergel P, Peterson K. Neutrophils and low-grade inflammation in the seemingly normal aging human lung. Mech Ageing Dev. 1998:104(2):169-181. DOI: https://doi.org/10.1016/S0047-6374(98)00065-7
Holgate ST. Rhinoviruses in the pathogenesis of asthma: The bronquial epitelium as a mayor disease target. J Allergy Clin Immunol. 2006;118(3):587-590.
Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. Br Med J. 1993;307(6910):982-986. Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1679193/
Delespesse G, De Maubege J, Kennes B, Nicaise R, Govaerts A. IgE mediated hypersensitivity in ageing. Clin Exp Allergy. 1977;7(2):155-160. DOI: http://dx.doi.org/10.1111/j.1365-2222.1977.tb01436.x
Jarvis D, Luczynska C, Chinn S, Potts J, Sunyer J, Janson C, et al. Change in prevalence of IgE sensitization and mean total IgE with age and cohort. J Allergy Clin Immunol. 2005;116(3):675-682.
King M, Bukantz S, Phillips S, Mohapatra SS, Tamulis T, Lockey RF. Serum total IgE an specific IgE to Dermatophagoides pteronyssinus, but not eosinophil cationic protein, are more likely to be elevated in elderly asthmatic patients. Allergy Asthma Proc. 2004;25(5):321-325.
Annema J, Sparrow D, O’Connor G, Rijcken B, Koëter GH, Postma DS, et al. Chronic respiratory symptoms and airway responsiveness to methacholine are associated with eosinophilia in older men. The normative aging study. Eur Respir J. 1995;8:62-69. DOI: http://dx.doi.org/10.1183/09031936.95.08010062
Mathur S, Schwantes E Jarjour NN, Busse WW. Age-related changes in eosinophil function in human subjects. Chest. 2008;133(2):412-419. DOI: http://dx.doi.org/10.1378/chest.07-2114
Thomas RA, Green RH, Brightling CE, Birring SS, Parker D, Wardlaw AJ, et al. The influence of age on induced sputum differential cell counts in normal subjects. Chest. 2004;126(6):1811-1814. DOI: http://dx.doi.org/10.1378/chest.126.6.1811
Nyenhuis SM, Schwantes EA, Evans MD, Mathur SK. Airway neutrophil inflammatory phenotype in older subjects with asthma. J Allergy Clin Immunol. 2010;125(5):1163-1165. DOI: http://dx.doi.org/10.1016/j.jaci.2010.02.015
Busse P, Kilaru K. Complexitus of diagnosis and treatment of allergic respiratory disease in the elderly. Drug Aging. 2009;26(1):1-22.
Al-Alawi, Hassan T, Chotermall S. Advances in the diagnosis and management of asthma in older adults. Am J Med. 2014;127:370-378. DOI: http://dx.doi.org/10.2165/0002512-200926010-00001
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