Carrieri Giuseppina, Marzi Erika, Olivieri Fabiola, Marchegiani Francesca, Cavallone Luca, Cardelli Maurizio, Giovagnetti Simona, Stecconi Rosalia, Molendini Cinzia, Trapassi Chiara, De Benedictis Giovanna, Kletsas Dimitri, Franceschi Claudio
I.N.R.C.A., Italian National Research Center on Aging, Ancona, Italy.
Aging Cell. 2004 Dec;3(6):443-8. doi: 10.1111/j.1474-9728.2004.00129.x.
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 beta1 (TGF-beta1) cytokine in inflammation and regulation of immune responses, the variability of the TGF-beta1 gene may affect longevity by playing a role in inflamm-aging. Two polymorphisms, G/A -800 and C/T -509, located in the 5' region, and two missense 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 Northern and Central Italy, including 172 centenarians and 247 younger controls. In addition, the effects of the TGF-beta1 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/C 869/C 915) was notably lower in centenarians than in younger individuals (P=0.007). Finally, active TGF-beta1 plasma levels were significantly increased in the elderly group, but no relationship with TGF-beta1 genotypes was observed. These results suggest that, at least in this population, the variability of the TGF-beta1 gene influences longevity and that the age-related increase in plasma levels of active TGF-beta1 seems not to be genetically regulated.
已发现多种促炎或抗炎细胞因子基因的序列变异会影响成功衰老和长寿。由于转化生长因子β1（TGF-β1）细胞因子在炎症和免疫反应调节中所起的作用，TGF-β1基因的变异性可能通过在炎症衰老中发挥作用来影响寿命。对位于5'区域的两个多态性位点G/A -800和C/T -509，以及位于信号肽区域的两个错义多态性位点T/C 869和G/C 915进行了分析，这两个错义多态性位点分别导致（Leu > Pro）10和（Arg > Pro）25的变化。研究对象为来自意大利北部和中部的419名受试者，其中包括172名百岁老人和247名年轻对照者。此外，在143名随机选择的受试者（包括73名百岁老人）中，研究了TGF-β1基因变异性对该细胞因子生物活性形式（自然加工）血浆水平的影响。就C等位基因和GC基因型而言，在+915位点发现了显著差异，百岁老人中的这两者均低于年轻对照者（P分别为0.034和0.028），但在百岁老人和对照者之间，其他测试的基因变体均无显著差异。此外，百岁老人中一种特定的单倍型组合（G -800/C -509/C 869/C 915）明显低于年轻人（P = 0.007）。最后，老年组中活性TGF-β1血浆水平显著升高，但未观察到与TGF-β1基因型的关系。这些结果表明，至少在该人群中，TGF-β1基因的变异性会影响寿命，并且活性TGF-β1血浆水平随年龄增长的增加似乎不受基因调控。
