The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, FOXO3 expression, and inflammatory cytokine levels in men and women. In agreement with earlier work, the FOXO3 longevity variant conferred protection against telomere shortening of peripheral blood mononuclear cells from adults aged 55 years and older. This was accompanied by higher levels of telomerase activity in mononuclear cells for carriers of the longevity-associated FOXO3 G-allele of SNP rs2802292 (P = 0.015). FOXO3 mRNA expression increased slightly with age in both young (P = 0.02) and old (P = 0.08) G-allele carriers. Older female G-allele carriers displayed a modest decline in levels of pro-inflammatory cytokine IL-6 with age (P = 0.07). In contrast, older male G-allele carriers displayed an age-dependent increase in levels of anti-inflammatory cytokine IL-10 with age (P = 0.04). Thus, FOXO3 may act through several different pro-longevity mechanisms, which may differ by age and sex.

FOXO3基因型与人类长寿的遗传关联已得到充分证实，但其机制尚不完全清楚。我们现在报告FOXO3长寿变异rs2802292与男性和女性端粒长度、端粒酶活性、 FOXO3表达和炎症细胞因子水平的关系。与早期的研究结果一致， FOXO3长寿变体赋予 55 岁及以上成年人外周血单核细胞端粒缩短的保护作用。与长寿相关的FOXO3 G等位基因 SNP rs2802292携带者的单核细胞中端粒酶活性水平较高（ P = 0.015）。在年轻 ( P = 0.02) 和老年 ( P = 0.08) G等位基因携带者中， FOXO3 mRNA 表达随年龄略有增加。老年女性G等位基因携带者的促炎细胞因子 IL-6 水平随着年龄的增长而适度下降（ P = 0.07）。相比之下，老年男性G等位基因携带者的抗炎细胞因子IL-10水平随着年龄的增长而呈年龄依赖性增加（ P = 0.04）。因此， FOXO3可能通过几种不同的长寿机制发挥作用，这些机制可能因年龄和性别而异。