Department of Medicine, Division of Endocrinology, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cells. 2020 Jun 1;9(6):1368. doi: 10.3390/cells9061368.
While the growth hormone/insulin-like growth factor-1 (GH/IGF-1) pathway plays essential roles in growth and development, diminished signaling via this pathway in model organisms extends lifespan and health-span. In humans, circulating IGF-1 and IGF-binding proteins 3 and 1 (IGFBP-3 and 1), surrogate measures of GH/IGF-1 system activity, have not been consistently associated with morbidity and mortality. In a prospective cohort of independently-living older adults ( = 840, mean age 76.1 ± 6.8 years, 54.5% female, median follow-up 6.9 years), we evaluated the age- and sex-adjusted hazards for all-cause mortality and incident age-related diseases, including cardiovascular disease, diabetes, cancer, and multiple-domain cognitive impairment (MDCI), as predicted by baseline total serum IGF-1, IGF-1/IGFBP-3 molar ratio, IGFBP-3, and IGFBP-1 levels. All-cause mortality was positively associated with IGF-1/IGFBP-3 molar ratio (HR 1.28, 95% CI 1.05-1.57) and negatively with IGFBP-3 (HR 0.82, 95% CI 0.680-0.998). High serum IGF-1 predicted greater risk for MDCI (HR 1.56, 95% CI 1.08-2.26) and composite incident morbidity (HR 1.242, 95% CI 1.004-1.538), whereas high IGFBP-1 predicted lower risk for diabetes (HR 0.50, 95% CI 0.29-0.88). In conclusion, higher IGF-1 levels and bioavailability predicted mortality and morbidity risk, supporting the hypothesis that diminished GH/IGF-1 signaling may contribute to human longevity and health-span.
虽然生长激素/胰岛素样生长因子-1（GH/IGF-1）途径在生长和发育中发挥着重要作用，但该途径在模型生物中的信号减弱会延长寿命和健康寿命。在人类中，循环中的 IGF-1 和 IGF 结合蛋白 3 和 1（IGFBP-3 和 1），GH/IGF-1 系统活性的替代测量指标，与发病率和死亡率没有一致关联。在一项独立生活的老年成年人前瞻性队列研究中（=840，平均年龄 76.1±6.8 岁，54.5%为女性，中位随访时间 6.9 年），我们评估了基线总血清 IGF-1、IGF-1/IGFBP-3 摩尔比、IGFBP-3 和 IGFBP-1 水平对全因死亡率和与年龄相关疾病（包括心血管疾病、糖尿病、癌症和多域认知障碍[MDCI]）发生率的年龄和性别调整危险比。全因死亡率与 IGF-1/IGFBP-3 摩尔比呈正相关（HR1.28，95%CI1.05-1.57），与 IGFBP-3 呈负相关（HR0.82，95%CI0.680-0.998）。高血清 IGF-1 预测 MDCI（HR1.56，95%CI1.08-2.26）和复合发病发病率（HR1.242，95%CI1.004-1.538）的风险更高，而高 IGFBP-1 预测糖尿病（HR0.50，95%CI0.29-0.88）的风险更低。总之，较高的 IGF-1 水平和生物利用度预测了死亡率和发病率的风险，支持了 GH/IGF-1 信号减弱可能导致人类长寿和健康寿命的假说。
