β 1 is associated with human longevity: a study in Italian centenarians

Summary − 800 and C/T − 509 , located in the 5'' region, and two mis- sense polymorphisms, T/C 869 and G/C 915 which change (Leu > Pro) 10 and (Arg > Pro) 25 , respectively, located in the signal peptide, were analysed in 419 subjects from North- ern and Central Italy, including 172 centenarians and 247 younger controls. In addition, the effects of the TGF-β 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 con- cerned, 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 signifi- cantly different between centenarians and controls. Moreover, a particular haplotype combination (G − 800 /C − 509 /C 869 /C 915 ) was notably lower in centenarians than in younger individuals ( P = 0.007). Finally, active TGF-β 1 plasma levels were significantly increased in the elderly group, but no relationship with TGF-β 1 genotypes was observed. These results suggest that, at least in this popu- lation, the variability of the TGF-β 1 gene influences lon- gevity and that the age-related increase in plasma levels of active TGF-β 1 seems not to be genetically regulated.