A gender–dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity

Bonafè, Massimiliano; Olivieri, Fabiola; Cavallone, Luca; Giovagnetti, Simona; Mayegiani, Francesca; Cardelli, Maurizio; Pieri, Carlo; Marra, Maurizio; Antonicelli, Roberto; Lisa, Rosamaria; Rizzo, Maria Rosaria; Paolisso, Giuseppe; Monti, Daniela; Franceschi, Claudio

doi:10.1002/1521-4141(200108)31:8<2357::aid-immu2357>3.3.co;2-o

Cited by 68 publications

(98 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The polymorphisms of the genes codifying these proteins are predictive on one hand in longevity, such as IL-6 -174G/C locus, confirming previous report by [18], on the other hand the same IL-6 polymorphism together with 1267 Hsp70-2 polymorphism are associated to cardiovascular diseases. TNF-a-308G/A is instead more related to risk of severe infection than longevity.…”

Section: Discussionsupporting

confidence: 86%

“…These findings clearly suggest that the genetic variations of the IL-6 -174G/C locus play a key role for the longevity also at functional level and confirm the existence of a major number of centenarians with C+ carriers than C-, as previously found by Bonafe et al [18]. In this context, an intriguing point is related to the low expression of the signal transducing component (gp130) of IL-6 receptor in centenarians in comparison with elderly despite high circulating levels of IL-6 [110], which in turn may be inactive in centenarians [105].…”

Section: Zinc-interleukin-6 Gene Interactionsupporting

confidence: 89%

“…On the other hand, the capability of C+ individuals (CC and CG genotypes) to produce low levels of IL-6 throughout life span appears to be beneficial for longevity, at least in men. The women have, conversely, high IL-6 serum levels later in life with respect to men independently from -174 C/G locus polymorphism [18].…”

Section: Zinc-interleukin-6 Gene Interactionmentioning

confidence: 95%

“…Bonafe et al [18] studied IL-6 promoter genetic variability at the -174 C/G locus and its effect on IL-6 levels in Italian 700 people aged 60-110 years, including 323 centenarians. Individuals who are genetically predisposed to produce high levels of IL-6 during ageing, i.e.…”

Section: Zinc-interleukin-6 Gene Interactionmentioning

confidence: 99%

See 3 more Smart Citations

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

View full text Add to dashboard Cite

The pivotal role played by zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-a) and heat shock proteins (HSP70-2) in ageing, successful ageing (nonagenarians) and the most common age-related diseases, such as atherosclerosis and infections, is now recognized. The polymorphisms of genes codifying proteins related to the inflammation are predictive on one hand in longevity, on the other hand they are associated with atherosclerosis or severe infections. Since the health lifespan has a strong genetic component, which in turn also affected by nutritional factors like zinc, the association of these polymorphisms with innate immune response, zinc ion bioavailability and Metallothioneins (MT) homeostasis is an useful tool to unravel the role played by zinc-gene interactions in longevity, especially due to the inability of MT in zinc release in ageing and chronic inflammation. In ageing, this last fact leads to depressed innate immune response for host defence. In contrast, in very old age the inflammation is lower with subsequent more zinc ion bioavailability, less MT gene expression and satisfactory innate immunity. Therefore, the zinc-gene (IL-6, TNF-a, Hsp70-2) interactions, via MT homeostasis, are crucial to achieve successful ageing. Human genes and longevityAgeing is a universal phenomenon that affects nearly all of animal species. According to Helfand and Rogina [69], ageing can be characterized as: (1) an inevitable consequence of being a multicellular organism; (2) associated with a random, passive decline in function; (3) leading to a global loss of homeostasis over time and (4) mortality increasing with ageing. Evolutionary studies on ageing have drawn the attention on the importance of the genetic mechanisms involved in somatic maintenance and repair that secure longevity [82]. Evidence from model organisms has indicated that subtle variation in the genes can dramatically influence lifespan. However, findings on potential candidate genetic mechanisms determining ageing and lifespan in model organisms are far to explain variations in human populations because phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar [86]. Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into accoun...

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Zinc-interleukin-6 Gene Interactionsupporting

confidence: 89%

Section: Zinc-interleukin-6 Gene Interactionmentioning

confidence: 95%

Section: Zinc-interleukin-6 Gene Interactionmentioning

confidence: 99%

See 2 more Smart Citations

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

View full text Add to dashboard Cite

show abstract

“…The presence of the rs1800795 C-allele has been associated with a mild phenotype of inflammation-triggering pathologies (Hefler et al 2005, Sawczenko et al 2005. The role of rs1800795 in longevity has been explored in the Italian population with conflicting results (Bonafè et al 2001;Capurso et al 2004;Christiansen et al 2004;Hurme et al 2005). Increased IL-6 is generally considered a negative modulator of longevity, as it correlates with disability and mortality (Gruenewald et al 2006;Jylhä et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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

Albani

Batelli

Polito

et al. 2009

AGE

View full text Add to dashboard Cite

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.

show abstract

The multiple facets of premature aging in rheumatoid arthritis

Straub¹,

Schölmerich²,

Cutolo³

2003

Arthritis & Rheumatism

View full text Add to dashboard Cite

Experimental analysis and numerical simulation of hydrodynamics and mass transfer in a turbulent oxygen–water bubbly shear layer is presented. The experimental data presents the structure of the averaged and fluctuating velocity fields as well as those of the gas volumetric fraction and the local dissolved oxygen concentration. Numerical simulations have been performed using Euler–Euler two‐fluid model that provides some specific modeling adapted for gas–liquid bubbly flows and allows a reasonable representation of the two‐phase flow structure (fields of average velocities and volumetric fractions of the two phases) as well as the important modulation of the turbulence in the two‐phase flow. With the improvements of two‐phase flow prediction, the averaged oxygen concentration field is also well predicted. The analysis of these results supports the pertinence of some improvements in two‐phase flow modeling and allows some proposals for further progress in the development of more general multiphase models for complex gas–liquid systems. © 2007 American Institute of Chemical Engineers AIChE J, 2007

show abstract

A gender–dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity

Cited by 68 publications

References 0 publications

Zinc–gene interaction related to inflammatory/immune response in ageing

Zinc–gene interaction related to inflammatory/immune response in ageing

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

The multiple facets of premature aging in rheumatoid arthritis

Contact Info

Product

Resources

About