Baltimore, MD 21287, USA.
J Gerontol A Biol Sci Med Sci. 2011 Jul;66(7):794-800. doi: 10.1093/gerona/glr058. Epub 2011 Apr 7.
The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans.
We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy.
During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho (<575 pg/mL) had an increased risk of death compared with participants in the highest tertile of plasma klotho (>763 pg/mL; hazards ratio 1.78, 95% confidence interval 1.20-2.63).
In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans.
衰老抑制基因 klotho 编码一种单次跨膜蛋白，已知在小鼠中过表达可延长寿命，而表达中断则类似于加速衰老。目前尚不清楚人类血浆中分泌型 klotho 蛋白水平与长寿之间是否存在关系。
我们在意大利托斯卡纳进行的一项基于人群的衰老纵向研究——INCHIANTI 研究中，测量了 804 名年龄大于或等于 65 岁的成年人的血浆 klotho 水平。
在 6 年的随访期间，194 名（24.1%）参与者死亡。在多变量 Cox 比例风险模型中，调整年龄、性别、教育程度、体重指数、身体活动、总胆固醇、高密度脂蛋白胆固醇、认知、25-羟维生素 D、甲状旁腺激素、血清钙、平均动脉压和慢性病后，血浆 klotho 水平最低三分位（<575 pg/mL）的参与者死亡风险较血浆 klotho 水平最高三分位（>763 pg/mL）的参与者增加（风险比 1.78，95%置信区间 1.20-2.63）。
在年龄较大的社区居住成年人中，血浆 klotho 是全因死亡率的独立预测因子。需要进一步的研究来阐明循环 klotho 如何通过潜在的生物学机制影响人类的长寿。
