Polymorphic variants of innate immunity genes in longevity and age-associated diseases

Abstract

Aging is one of the most complex biological phenomena that affects all human physiological systems, including the immune system, causing the process of immunosenescence. One of the manifestations of immunosenescence is the so-called inflammaging, which is considered an important risk factor for morbidity and mortality in the elderly, since chronic inflammation underlies age-related diseases. Genetic variants of pro-/anti-inflammatory factors of the innate immune response can be associated with the level of the inflammation and influence the predisposition to age-associated diseases, survival and achievement of longevity, altering the host’s response to the environment and endogenous stress. The review presents data on the association of polymorphic variants of innate immunity genes – TLR, NLRP3, pro-/anti-inflammatory cytokines – with longevity and age-associated pathology.

Keywords:immunosenescence; inflammaging; innate immunity; polymorphic variants of genes; TLR; NLRP3; proinflammatory cytokines; longevity; age-associated diseases

For citation. Artemyeva O.V., Gankovskaya L.V. Polymorphic variants of innate immunity genes in longevity and age-associated diseases. Immunologiya. 2022; 43 (3): 333–42. DOI: https://doi.org/10.33029/0206-4952-2022-43-3-333-342 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. Authors declare no conflict of interests.

Authors contribution. General concept of the review – Gankovskaya L.V.; search and analysis of literature, writing the text – Artemyeva O.V., Gankovskaya L.V.; editing – Artemyeva O.V.

References

1. Kennedy B.K., Berger S.L., Brunet A., Campisi J., Cuervo A.M., Epel E.S., et al. Geroscience: linking aging to chronic disease. Cell. 2014; 159: 709–13. DOI: https://doi.org/10.1016/j.cell.2014.10.039

2. Lopez-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G. The hallmarks of aging. Cell. 2013; 153: 1194–217. DOI: https://doi.org/10.1016/j.cell.2013.05.039

3. Rodrigues L.P., Teixeira V.R., Alencar-Silva T., Simonassi-Paiva B., Pereira R.W., Pogue R., et al. Hallmarks of aging and immunosenescence: connecting the dots. Cytokine Growth Factor Rev. 2021; 59: 9–21. DOI: https://doi.org/10.1016/j.cytogfr.2021.01.006

4. Barbe-Tuana F., Funchal G., Schmitz C.R.R., Maurmann R.M., Bauer M.E. The interplay between immunosenescence and age-related diseases. Semin. Immunopathol. 2020; 42 (5): 545–57. DOI: https://doi.org/10.1007/s00281-020-00806-z

5. Sayed N., Huang Y., Nguyen K., Krejciova-Rajaniemi Z., Grawe A.P., Gao T., et al. An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging. Nat. Aging. 2021; 1: 598–615.

6. Franceschi C., Bonafe M., Valensin S., Olivieri F., De Luca M., Ottaviani E., De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci. 2000; 908: 208–18.

7. Franceschi C., Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci. 2014; 69 (1): S4–9. DOI: https://doi.org/10.1093/gerona/glu057

8. Fulop T., Witkowski J.M., Olivieri F., Larbi A. The integration of inflammaging in age-related diseases. Semin. Immunol. 2018; 40: 17–35.

9. Gankovskaya L.V., Artem’eva O.V., Namazova-Baranova L.S., Semenkov V.F., Svitich O.A., Grechenko V.V. Immunological aspects of aging and age-associated pathology. Moscow: Pediatr, 2021: 156 с. ISBN: 978-5-6042576-7-8. (in Russian)

10. Pawelec G., Bronikowski A., Cunnane S.C., Ferrucci L., Franceschi C., Fülop T., et al. The conundrum of human immune system «senescence». Mech. Ageing Dev. 2020; 192: 111357. DOI: https://doi.org/10.1016/j. mad.2020.111357

11. Fulop T., Larbi A., Hirokawa K., Cohen A.A., Witkowski J.M. Immunosenescence is both functional/adaptive and dysfunctional/maladaptive. Semin. Immunopathol. 2020; 42 (5): 521–36. DOI: https://doi.org/10.1007/s00281-020-00818-9

12. Franceschi C., Garagnani P., Morsiani C., Conte M., Santoro A., Grignolio A., Monti D., Capri M., Salvioli S. The continuum of aging and age-related diseases: common mechanisms but different rates. Front. Med. 2018; 5: 61. DOI: https://doi.org/10.3389/fmed.2018.00061

13. Moskalev A.A., Aliper A.M., Smit-McBride Z., Buzdin A., Zhavoronkov A. Genetics and epigenetics of aging and longevity. Cell Cycle. 2014; 13: 1063–77. DOI: https://doi.org/10.4161/cc.28433

14. Pawelec G. The human immunosenescence phenotype: does it exist? Semin. Immunopathol. 2020; 42 (5): 537–44. DOI: https://doi.org/10.1007/s00281-020-00810-3

15. Franceschi C., Capri M., Monti D., et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 2007; 128 (1): 92–105.

16. Williams G.C. Pleiotropy, natural selection, and the evolution of senescence. Evolution. 1957; 11: 398–411.

17. Capri M., Salvioli S., Monti D., Caruso C., Candore G., Vasto S., et al. Human longevity within an evolutionary perspective: the peculiar paradigm of a post-reproductive genetics. Exp. Gerontol. 2008; 43: 53–60. DOI: https://doi.org/10.1016/j.exger.2007.06.004

18. Vasto S., Candore G., Balistreri C.R., Caruso M., Colonna-Romano G., Grimaldi M.P., et al. Inflammatory networks in ageing, age-related diseases and longevity. Mech. Ageing Dev. 2007; 128: 83–91. DOI: https://doi.org/10.1016/j.mad.2006.11.015

19. Solana R., Tarazona R., Gayoso I., Lesur O., Dupuis G., Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin. Immunol. 2012; 24 (5): 331–41.

20. Tilstra J.S., Clauson C.L., Niedernhofer L.J., Robbins P.D. NF-κB in aging and disease. Aging Dis. 2011; 2 (6): 449–65.

21. Balistreri C.R., Caruso C., Listi F., Colonna-Romano G., Lio D., Candore G. LPS-mediated production of pro/anti-inflammatory anti-inflammatory cytokines and eicosanoids in whole blood samples: biological effects of +896A/G TLR4 polymorphism in a Sicilian population of healthy subjects. Mech. Ageing Dev. 2011; 132: 86–92.

22. Balistreri C.R., Colonna-Romano G., Lio D., Candore G., Caruso C. TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases. J. Clin. Immunol. 2009; 29: 406–15.

23. Jablonska A., Studzinska M., Szenborn L., Wisniewska-Ligier M., Karlikowska-Skwarnik M., Gesicki T., Paradowska E. TLR4 896A/G and TLR9 1174G/A polymorphisms are associated with the risk of infectious mononucleosis. Sci. Rep. 2020; 10 (1): 13154. DOI: https://doi.org/10.1038/s41598-020-70129-4

24. Balistreri C.R., Candore G., Colonna-Romano G., Lio D., Caruso M., Hoffmann E., Franceschi C., Caruso C. Role of Toll-like receptor 4 in acute myocardial infarction and longevity. JAMA. 2004; 292: 2339–40.

25. Balistreri C.R., Candore G., Accardi G., Bova M., Buffa S., Bulati M., et al. Genetics of longevity. data from the studies on Sicilian centenarians. Immun. Ageing. 2012; 9: 8.

26. Balistreri C.R., Grimaldi M.P., Chiappelli M., Licastro F., Castiglia L., Listi F., Vasto S., Lio D., Caruso C., Candore G. Association between the polymorphisms of TLR4 and CD14 genes and Alzheimer’s disease. Curr. Pharm. Des. 2008; 14: 2672–7.

27. Kutikhin A.G. Impact of Toll-like receptor 4 polymorphisms on risk of cancer. Hum. Immunol, 2011; 72: 193–206.

28. Liu F., Lu W., Qian Q., Qi W., Hu J., Feng B. Frequency of TLR 2, 4, and 9 gene polymorphisms in Chinese population and their susceptibility to type 2 diabetes and coronary artery disease. Biomed. Biotechnol, 2012; 2012: 373945.

29. Zhang L.S., Qin H.J., Guan X., Zhang K., Liu Z.R. The TLR9 gene polymorphisms and the risk of cancer: evidence from a meta-analysis. PLoS One. 2013; 8 (8): e71785.

30. Gankovskaya L.V., Svitich O.A., Artem’eva O.V., Miroshnichenkova A.M., Rusanova K.V. Association of polymorphisms in innate immunity genes TLR9 and DEFB1 with human longevity. Byulleten’ eksperimental’noi biologii i meditsiny. 2015; 159 (1): 77–80. (in Russian)

31. Latz E., Duewell P. NLRP3 inflammasome activation in inflammaging. Semin. Immunol. 2018; 40: 61–73.

32. Gritsenko A., Green J.P., Brough D., Lopez-Castejon G. Mechanisms of NLRP3 priming in inflammaging and age related diseases. Cytokine Growth Factor Rev. 2020; 55: 15–25.

33. Fusco R., Siracusa R., Genovese T., Cuzzocrea S., Di Paola R. Focus on the Role of NLRP3 inflammasome in diseases Int. J. Mol. Sci. 2020; 21: 4223. DOI: https://doi.org/10.3390/ijms21124223

34. Lee Y.H., Bae S.C. Association between functional NLRP3 polymorphisms and susceptibility to autoimmune and inflammatory diseases: a meta-analysis. Lupus. 2016; 25 (14): 1558–66.

35. Zhang Q., Fan H.W., Zhang J.Z., Wang Y.M., Xing H.J. NLRP3 rs35829419 polymorphism is associated with increased susceptibility to multiple diseases in humans. Genet. Mol. Res. 2015; 14 (4): 13 968–80.

36. Verma D., Sarndahl E., Andersson H., Eriksson P., Fredrikson M., Jonsson J.I., et al. The Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to excessive interleukin-1β and IL-18 production. PLoS One. 2012; 7: e34977.

37. Varghese G.P., Fransen K., Hurtig-Wennlof A., Bengtsson T., Jansson J.H., Sirsjo A. Q705K variant in NLRP3 gene confers protection against myocardial infarction in female individuals. Biomed. Rep. 2013; 1 (6): 879–82.

38. Marín-Aguilar F., Lechuga-Vieco A.V., Alcocer-Gomez E., Castejon-Vega B., Lucas J., et al. NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice. Aging Cell. 2020; 19 (1): e13050.

39. Roubenoff R., Parise H., Payette H.A., Abad L.W., D’Agostino R., Jacques P.F., Wilson P.W., Dinarello C.A., Harris T.B. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am. J. Med. 2003; 115 (6): 429–35.

40. Rea I.M., Gibson D.S., McGilligan V., McNerlan S.E., Alexander H.D., Ross O.A. Age and age-related diseases: role of inflammation triggers and cytokines. Front. Immunol. 2018; 9: 586.

41. Singh M., Mastana S., Singh S., Juneja P.K., Kaur T., Singh P. Promoter polymorphisms in IL-6 gene influence pro-inflammatory cytokines for the risk of osteoarthritis. Cytokine. 2020; 127: 154985. DOI: https://doi.org/10.1016/j.cyto.2020.154985

42. Christiansen L., Bathum L., Andersen-Ranberg K., Jeune B., Christensen K. Modest implication of interleukin-6 promoter polymorphisms in longevity. Mech. Ageing Dev. 2004; 125: 391–5.

43. Hurme M., Lehtimaki T., Jylha M., Karhunen P.J., Hervonen A. Interleukin-6 −174G/C polymorphism and longevity: a follow-up study. Mech. Ageing Dev. 2005; 126: 417–8.

44. Bonafe M., Olivieri F., Cavallone L., Giovagnetti S., Mayegiani F., Cardelli M., et al. A genderdependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur. J. Immunol. 2001; 31: 2357–61.

45. Capurso C., Solfrizzi V., D’Introno A., Colacicco A.M., Capurso S.A., Semeraro C., Capurso A., Panza F. Interleukin 6 variable number of tandem repeats (VNTR) gene polymorphism in centenarians. Ann. Hum. Genet. 2007; 71: 843–8.

46. Di Bona D., Vasto S., Capurso C., et al. Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis. Ageing Res. Rev. 2009; 8: 36–42.

47. Hou H., Wang C., Sun F., Zhao L., Dun A., Sun Z. Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis. Inflamm. Res. 2015; 64: 707–20.

48. Li L., Li E., Zhang L.H., Jian L.G., Liu H.P., Wang T. IL-6-174G/C and IL-6-572C/G polymorphisms are associated with increased risk of coronary artery disease. Genet. Mol. Res. 2015; 14: 8451–7.

49. Cardelli M., Cavallone L., Marchegiani F., Oliveri F., Dato S., Montesanto A., Lescai F., Lisa R., De Benedictis G., Franceschi C. A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism. J. Gerontol. A Biol. Sci. Med. Sci. 2008; 63: 454–60.

50. Mustafina О.Е., Pauk V.V., Mustafina R.Sh., Tuktarova I.A., Nasibullin T.R. Polymorphism of cytokine genes and human longevity. Uspekhi gerontologii. 2010; 23 (3): 339–45. (in Russian)

51. Antonicelli R., Olivieri F., Cavallone L., Spazzafumo L., Bonafè M., Marchegiani F., et al. Tumor necrosis factor-alpha gene -308G>A polymorphism is associated with ST-elevation myocardial infarction and with high plasma levels of biochemical ischemia markers Coron. Artery Dis. 2005; 16: 489–93.

52. Zhao Y., Li Z., Zhang L., Zhang Y., Yang Y., Tang Y., et al. The TNF-alpha -308G/A polymorphism is associated with type 2 diabetes mellitus: an updated meta-analysis. Mol. Biol. Rep. 2014; 41: 73–83.

53.Zhang Y., Cui X., Ning L., Wei D. The effects of tumor necrosis factor-α (TNF-α) rs1800629 and rs361525 polymorphisms on sepsis risk. Oncotarget. 2017; 8: 111 456–69.

54.Shi C., Zhao H. Association between tumor necrosis factor-308 G/A polymorphism and chronic obstructive pulmonary disease risk in Chinese population: evidence from a meta-analysis. Clin. Lab. 2019; 65 (10).

55.Kang S.W., Kim S.K., Han Y.R., Hong D., Chon J., Chung J.H., Hong S.J., Park M.S., Ban J.Y. Promoter polymorphism (-308G/A) of tumor necrosis factor-alpha (TNF-α) gene and asthma risk: an updated meta-analysis. Genet. Test. Mol. Biomarkers. 2019; 23: 363–72.

56.Santos N.C.D., Gomes T.N., Gois I.A.F., Oliveira J.S., Coelho L.F.L., Ferreira G.P., Silva F.R.P.D., Pereira A.C.T.D.C. Association of single nucleotide polymorphisms in TNF-α (-308G/A and -238G/A) to dengue: case-control and meta-analysis study. Cytokine. 2020; 134: 155183.

57.Saleh A., Sultan A., Elashry M.A., Farag A., Mortada M.I., Ghannam M.A., Saed A.M., Ghoneem S. Association of TNF-α G-308 a promoter polymorphism with the course and outcome of COVID-19 patients. Immunol. Invest. 2022; 51 (3): 546–57.

58.Lio D., Scola L., Crivello A., Bonafe M., Franceschi, C., Olivieri F., Colonna-Romano G., Candore G., Caruso C. Allele frequencies of +874 T-&A single nucleotide polymorphism at the first intron of interferon gamma gene in a group of Italian centenarians. Exp. Gerontol. 2002; 37: 315–9. DOI: https://doi.org/10.1016/s0531-5565(01)00198-x

59.Lio D., Scola L., Crivello A., Colonna-Romano G., Candore G., Bonafe M., Cavallone L., Franceschi C., Caruso C. Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun. 2002; 3: 30–3. DOI: 10.1038/sj.gene.6363827

60.Lio D., Scola L., Crivello A., Colonna-Romano G., Candore G., Bonafe M., Cavallone L., Marchegiani F., Olivieri F., Franceschi C., Caruso C. Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10-1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP. J. Med. Genet. 2003; 40: 296–9. DOI: https://doi.org/10.1136/jmg.40.4.296

61.Naumova E., Ivannova M., Pawelec G. Immunogenetics of ageing. Int. J. Immunogenet. 2011; 38: 373–81.

62.Khabour O.F., Barnawi J.M. Association of longevity with IL-10 -1082 G⁄A and TNF-alpha -308 G⁄A polymorphisms. Int. J. Immunogenet. 2010; 37: 293–8.

63.Lio D., Licastro F., Scola L., Chiappelli M., Grimaldi L.M., Crivello A., Colonna-Romano G., Candore G., Franceschi C., Caruso C. Interleukin-10 promoter polymorphism in sporadic Alzheimer’s disease. Genes Immun. 2003; 4 (3): 234–8.

64.Lio D., Candore G., Crivello A., Scola L., Colonna-Romano G., Cavallone L., et al. Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease. J. Med. Genet. 2004; 41: 790–4.

65.Lio D., Scola L., Giarratana R.M., Candore G., Colonna-Romano G., Caruso C., Balistreri C.R. SARS CoV2 infection. The longevity study perspectives. Ageing Res. Rev. 2021; 67: 101299. DOI: https://doi.org/10.1016/j.arr.2021.101299

66.Franceschi C., Salvioli S., Garagnani P., de Eguileor M., Monti D., Capri M. Immunobiography and the heterogeneity of immune responses in the elderly: a focus on inflammaging and trained immunity. Front. Immunol. 2017; 8: 982. DOI: https://doi.org/10.3389/fimmu.2017.00982

67.Netea M.G., Domínguez-Andrés J., Barreiro L.B., Chavakis T., Divangahi M., Fuchs E., Joosten L.A.B., van der Meer J.W.M., Mhlanga M.M., Mulder W.J.M., Riksen N.P., Schlitzer A., Schultze J.L., Stabell Benn C., Sun J.C., Xavier R.J., Latz E. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol. 2020; 20 (6): 375–88. DOI: https://doi.org/10.1038/s41577-020-0285-6

EDITOR-IN-CHIEF
EDITOR-IN-CHIEF
Musa R. Khaitov

Corresponding member of Russian Academy of Sciences, MD, Professor, Director of the NRC Institute of Immunology FMBA of Russia

Вскрытие
Medicine today

II Всероссийская конференция с международным участием "Воспаление глаза" 12 ноября 2022 года, Москва Воспалительные заболевания глаза - широко распространенная и многогранная проблема, с которой может столкнуться в своей практике любой специалист. Найти оптимальные алгоритмы...

Масштабное событие в области дерматовенерологии и косметологии - II конференция InteDeCo 2022 "Интегративная дерматовенерология и косметология. Новые стандарты взаимодействия" - состоится 16-17 декабря 2022 года. Программа мероприятия пройдет на современной...

VIII Московский Городской Съезд педиатров с межрегиональным и международным участием "Трудный диагноз в педиатрии" Приглашаем педиатров, детских эндокринологов, реаниматологов, гинекологов, неонатологов, кардиологов, хирургов, урологов, психологов, специалистов по лучевой...


JOURNALS of «GEOTAR-Media»