SpringerLink
Log in

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

  • Published:
AGE Aims and scope Submit manuscript

Abstract

The transcription rate of interleukin-6 (IL-6) can be reduced by the C-allele of a polymorphism (rs1800795) located in the 5′-flanking region of the IL-6 gene (NM_000600), and IL-6 plasma levels increase with age. We assembled an elderly Italian population [“The Treviso Longeva (Trelong) study”, age range 70–106 years, n = 668 subjects] and assessed rs1800795 genotype and plasma IL-6 concentrations. The rs1800795 genotype was also assessed in an independent Italian study (“Milan” study, age range 70–96, n = 245 subjects). To verify an age- or sex-specific effect of rs1800795 genotype we compared people younger (70–85) and older (85+) than 85 years of age. We found a significant reduction in the frequency of rs1800795 C/C genotype in 85+ men from the Trelong study, while in the Milan study this data did not reach significance. However, considering the two studies together, the frequency of the rs1800795 C/C genotype was significantly lower in 85+ than in 70–85 males (4.0% and 10.7%, respectively), while it remained unchanged in females. As for IL-6 plasma levels, after a multivariate analysis to control for confounders, a correlation between age and plasma IL-6 concentrations was revealed (P < 0.0001). An increase in circulating IL-6 levels in the entire 85+ group compared to the 70–85 group (P < 0.05, Tukey′s test) was also noticed. We suggest a sex-specific pattern for genetic variability linked to inflammatory response and longevity, consistent with the age-related increase in IL-6.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Antebi A (2007) Genetics of aging in Caenorhabditis elegans. PLoS Genet 3:1565–1571. doi:10.1371/journal.pgen.0030129

    Article  PubMed  CAS  Google Scholar 

  • Barbieri M, Bonafè M, Rizzo MR, Ragno E, Olivieri F, Marchegiani F, Franceschi C, Paolisso G (2004) Gender specific association of genetic variation in peroxisome proliferator-activated receptor (PPAR) gamma-2 with longevity. Exp Gerontol 39:1095–1100. doi:10.1016/j.exger.2004.03.034

    Article  PubMed  CAS  Google Scholar 

  • Bonafè M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C (2001) A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 31:2357–2361. doi:10.1002/1521-4141(200108) 31:8 &lt; 2357::AID-IMMU2357 &gt; 3.0.CO;2-X

    Article  PubMed  Google Scholar 

  • Capurso C, Solfrizzi V, D′Introno A, Colacicco AM, Capurso SA, Semeraro C, Capurso A, Panza F (2004) Interleukin 6-174 G/C promoter gene polymorphism in centenarians: no evidence of association with human longevity or interaction with apolipoprotein E alleles. Exp Gerontol 39:1109–1114. doi:10.1016/j.exger.2004.03.037

    Article  PubMed  CAS  Google Scholar 

  • Caruso C, Lio D, Cavallone L, Franceschi C (2004) Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci 1028:1–13. doi:10.1196/annals.1322.001

    Article  PubMed  CAS  Google Scholar 

  • Cederholm T, Persson M, Andersson P, Stenvinkel P, Nordfors L, Madden J, Vedin I, Wretlind B, Grimble RF, Palmblad J (2007) Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. J Intern Med 262:215–223. doi:10.1111/j.1365-2796.2007.01803.x

    Article  PubMed  CAS  Google Scholar 

  • Christiansen L, Bathum L, Andersen-Ranberg K, Jeune B, Christensen K (2004) Modest implication of interleukin-6 promoter polymorphisms in longevity. Mech Ageing Dev 125:391–395. doi:10.1016/j.mad.2004.03.004

    Article  PubMed  CAS  Google Scholar 

  • Colinet B, Jacot W, Bertrand D, Lacombe S, Bozonnat MC, Daures JP, Pujol JL (2005) A new simplified comorbidity score as a prognostic factor in non-small-cell lung cancer patients: description and comparison with the Charlson′s index. Br J Cancer 93:1098–1105. doi:10.1038/sj.bjc.6602836

    Article  PubMed  CAS  Google Scholar 

  • Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376. doi:10.1172/JCI2629

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000a) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254

    Article  PubMed  CAS  Google Scholar 

  • Franceschi C, Motta L, Valensin S, Rapisarda R, Franzone A, Berardelli M, Motta M, Monti D, Bonafè M, Ferrucci L, Deiana L, Pes GM, Carru C, Desole MS, Barbi C, Sartoni G, Gemelli C, Lescai F, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Gueresi P, Cossarizza A, Troiano L, Pini G, Sansoni P, Passeri G, Lisa R, Spazzafumo L, Amadio L, Giunta S, Stecconi R, Morresi R, Viticchi C, Mattace R, De Benedictis G, Baggio G (2000b) Do men and women follow different trajectories to reach extreme longevity? Italian Multicenter Study on Centenarians (IMUSCE) Aging (Milano) 12:77–84

    CAS  Google Scholar 

  • Gallucci M, Amici GP, Ongaro F, Gajo GB, De Angeli S, Forloni GL, Albani D, Prato F, Polito L, Zanardo A, Regini C (2007a) Associations of the plasma interleukin 6 (IL-6) levels with disability and mortality in the elderly in the Treviso Longeva (Trelong) study. Arch Gerontol Geriatr 44:193–198. doi:10.1016/j.archger.2007.01.026

    Article  PubMed  CAS  Google Scholar 

  • Gallucci M, Ongaro F, Bresolin F, Bernardi U, Salvato C, Minello A, Amici GP, Barasciutti E, Mazzuco S, Gajo GB, De Angeli S, Forloni GL, Albani D, Zanardo A, Regini C (2007b) The Treviso Longeva (Trelong) study: a biomedical, demographic, economic and social investigation on people 70 years and over in a typical town of North-East of Italy. Arch Gerontol Geriatr 44:173–192. doi:10.1016/j.archger.2007.01.025

    Article  PubMed  Google Scholar 

  • Giacconi R, Cipriano C, Albanese F, Boccoli G, Saba V, Olivieri F, Franceschi C, Mocchegiani E (2004) The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing. Exp Gerontol 39:621–628. doi:10.1016/j.exger.2003.12.013

    Article  PubMed  CAS  Google Scholar 

  • Gruenewald TL, Seeman TE, Ryff CD, Karlamangla AS, Singer BH (2006) Combinations of biomarkers predictive of later life mortality. Proc Natl Acad Sci USA 103:14158–14163. doi:10.1073/pnas.0606215103

    Article  PubMed  CAS  Google Scholar 

  • Hefler LA, Grimm C, Lantzsch T, Lampe D, Leodolter S, Koelbl H, Heinze G, Reinthaller A, Tong-Cacsire D, Tempfer C, Zeillinger R (2005) Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women. Clin Cancer Res 11:5718–5721. doi:10.1158/1078-0432.CCR-05-0001

    Article  PubMed  CAS  Google Scholar 

  • Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419:808–814. doi:10.1038/nature01135

    Article  PubMed  CAS  Google Scholar 

  • Herskind A, McGue M, Holm N, Sørensen T, Harvald B, Vaupel J (1996) The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870-1900. Hum Genet 97:319–323. doi:10.1007/BF02185763

    Article  PubMed  CAS  Google Scholar 

  • Hurme M, Lehtimäki T, Jylhä M, Karhunen PJ, Hervonen A (2005) Interleukin-6-174G/C polymorphism and longevity: a follow-up study. Mech Ageing Dev 126:417–418. doi:10.1016/j.mad.2004.10.001

    Article  PubMed  CAS  Google Scholar 

  • Jylhä M, Paavilainen P, Lehtimäki T, Goebeler S, Karhunen PJ, Hervonen A, Hurme M (2007) Interleukin-1 receptor antagonist, interleukin-6, and C-reactive protein as predictors of mortality in nonagenarians: the vitality 90 + study. J Gerontol A Biol Sci Med Sci 62:1016–1021

    PubMed  Google Scholar 

  • Kim SK (2007) Common aging pathways in worms, flies, mice and humans. J Exp Biol 210:1607–1612. doi:10.1242/jeb.004887

    Article  PubMed  CAS  Google Scholar 

  • Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafè M, Cavallone L, Franceschi C, Caruso C (2002) Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun 3:30–33. doi:10.1038/sj.gene.6363827

    Article  PubMed  CAS  Google Scholar 

  • Lubrano V, Cocci F, Battaglia D, Papa A, Marraccini P, Zucchelli GC (2005) Usefulness of high-sensitivity IL-6 measurement for clinical characterization of patients with coronary artery disease. J Clin Lab Anal 19:110–114. doi:10.1002/jcla.20061

    Article  PubMed  CAS  Google Scholar 

  • Mastorakos G, Ilias I (2006) Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. Ann N Y Acad Sci 1088:373–381. doi:10.1196/annals.1366.021

    Article  PubMed  CAS  Google Scholar 

  • Pes GM, Lio D, Carru C, Deiana L, Baggio G, Franceschi C, Ferrucci L, Oliveri F, Scola L, Crivello A, Candore G, Colonna-Romano G, Caruso C (2004) Association between longevity and cytokine gene polymorphisms. A study in Sardinian centenarians. Aging Clin Exp Res 16:244–248

    PubMed  CAS  Google Scholar 

  • Sawczenko A, Azooz O, Paraszczuk J, Idestrom M, Croft NM, Savage MO, Ballinger AB, Sanderson IR (2005) Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the -174 IL-6 G/C polymorphism in children. Proc Natl Acad Sci USA 102:13260–13265. doi:10.1073/pnas.0503589102

    Article  PubMed  CAS  Google Scholar 

  • Van Bodegom D, May L, Meij HJ, Westendorp RG (2007) Regulation of human life histories: the role of the inflammatory host response. Ann N Y Acad Sci 1100:84–97. doi:10.1196/annals.1395.007

    Article  PubMed  CAS  Google Scholar 

  • vB Hjelmborg J, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, Kaprio J, Pedersen NL, Christensen K (2006) Genetic influence on human lifespan and longevity. Hum Genet 119:312–321

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Veneto Region, the Treviso Municipality, Treviso Province and Cassamarca Foundation. The support of Monzino Foundation (Milan, Italy) and “Centro Dino Ferrari” (Milan, Italy) is also acknowledged. We are grateful to all patients who kindly agreed to participate in this study and to J.D. Baggott for manuscript editing. L.P. is recipient of a fellowship from “Golgi Cenci Foundation”, Milan, Italy.

Author information

Authors and Affiliations

  1. Department of Neuroscience, Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156, Milan, Italy

    Diego Albani, Sara Batelli, Letizia Polito, Francesca Prato, Marzia Pesaresi & Gianluigi Forloni

  2. ARGEI, Interdisciplinary Geriatric Research Association, Trento Trieste Avenue, 19, 31100, Treviso, Italy

    Giovanni Battista Gajo, Sergio De Angeli, Andrea Zanardo & Maurizio Gallucci

  3. Trasfusional Center Regional Hospital Treviso, Piazza Ospedale, 1, 31100, Treviso, Italy

    Giovanni Battista Gajo & Sergio De Angeli

  4. Clinical Chemistry Laboratory Regional Hospital Treviso, Piazza Ospedale, 1, 31100, Treviso, Italy

    Andrea Zanardo

  5. Department of Neurological Sciences, Dino Ferrari Centre, Ospedale Maggiore Policlinico, University of Milan, via F. Sforza, 35, 20122, Milan, Italy

    Daniela Galimberti & Elio Scarpini

  6. Treviso General Hospital, Piazza Ospedale, 1, 31100, Treviso, Italy

    Maurizio Gallucci

Authors
  1. Diego Albani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Batelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Letizia Polito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francesca Prato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marzia Pesaresi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giovanni Battista Gajo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sergio De Angeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea Zanardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daniela Galimberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Elio Scarpini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Maurizio Gallucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gianluigi Forloni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diego Albani.

About this article

Cite this article

Albani, D., Batelli, S., Polito, L. et al. Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism. AGE 31, 155–162 (2009). https://doi.org/10.1007/s11357-009-9092-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-009-9092-5

Keywords

Search

Navigation