The G/C₉₁₅ polymorphism of transforming growth factor 1 is associated with human longevity: a study in Italian centenarians

Authors: Giuseppina Carrieri; Erika Marzi; Fabiola Olivieri¹; Francesca Marchegiani¹; Luca Cavallone¹; Maurizio Cardelli¹; Simona Giovagnetti¹; Rosalia Stecconi¹; Cinzia Molendini²; Chiara Trapassi²; Giovanna De Benedictis³; Dimitri Kletsas⁴; Claudio Franceschi

Source: Aging Cell, Volume 3, Number 6, December 2004 , pp. 443-448(6)

Publisher: Wiley-Blackwell

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Abstract:

Summary

Sequence variations in a variety of pro- or anti-inflammatory cytokine genes have been found to influence successful aging and longevity. Because of the role played by the transforming growth factor bgr

1 (TGF-

1) cytokine in inflammation and regulation of immune responses, the variability of the TGF-1 gene may affect longevity by playing a role in inflamm-aging. Two polymorphisms, G/A_-800 and C/T_-509, located in the 5 prime

region, and two missense polymorphisms, T/C₈₆₉ and G/C₉₁₅ which change (Leu > Pro)₁₀ and (Arg > Pro)₂₅, respectively, located in the signal peptide, were analysed in 419 subjects from Northern and Central Italy, including 172 centenarians and 247 younger controls. In addition, the effects of the TGF-1 genetic variability on plasma levels of the biologically active form (naturally processed) of this cytokine were studied in 143 randomly selected subjects, including 73 centenarians. Significant differences were found at the +915 site as far as the C allele and GC genotype were concerned, both of them being lower in centenarians than in young controls (P = 0.034 and 0.028, respectively), but none of the other tested genetic variants was significantly different between centenarians and controls. Moreover, a particular haplotype combination (G_-800/C_-509/C₈₆₉/C₉₁₅) was notably lower in centenarians than in younger individuals (P = 0.007). Finally, active TGF- bgr

1 plasma levels were significantly increased in the elderly group, but no relationship with TGF-1 genotypes was observed. These results suggest that, at least in this population, the variability of the TGF-1 gene influences longevity and that the age-related increase in plasma levels of active TGF- bgr

1 seems not to be genetically regulated.

Keywords: aging; centenarians; inflammation; longevity; polymorphism; TGF- bgr 1

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1474-9728.2004.00129.x

Affiliations: 1: I.N.R.C.A., Italian National Research Center on Aging, Ancona, Italy 2: C.I.G., Interdepartmental Center ‘L. Galvani’ for Integrated Studies on Bioinformatics, Biophysics, and Biocomplexity, University of Bologna, Bologna, Italy 3: Department of Cell Biology, University of Calabria, Rende, Italy 4: Institute of Biology, N.C.S.R. Demokritos, Athens, Greece

Publication date: 2004-12-01