Balasubramanian Priya, Longo Valter D
Longevity Institute, Davis School of Gerontology, University of Southern California, Los Angeles, California, United States.
Longevity Institute, Davis School of Gerontology, University of Southern California, Los Angeles, California, United States; IFOM, FIRC Institute of Molecular Oncology, Milano, Italy.
Growth Horm IGF Res. 2016 Jun;28:66-8. doi: 10.1016/j.ghir.2016.01.001. Epub 2016 Jan 7.
Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.
包括酵母和果蝇在内的简单生物，若其IGF-1和Tor-S6K信号通路发生突变，就会发育成侏儒，对毒素具有高度抵抗力，且寿命可延长至多两倍。同样，生长激素-IGF-I轴存在缺陷的侏儒小鼠也寿命较长，且不易患病。我们最近报告称，患有生长激素受体缺陷（GHRD）的人很少患癌症或糖尿病。这些发现与Tor-S6K信号通路缺陷导致侏儒症并保护DNA的作用相符。由于蛋白质限制会降低生长激素释放激素-IGF-1轴和Tor-S6K的活性，我们在美国疾病控制与预防中心（CDC）数据库中对6000多名美国受试者的蛋白质摄入量、疾病和死亡率之间的联系进行了研究。年龄在50至65岁之间且报告高蛋白摄入量的受访者，其IGF-I水平升高，全因死亡率风险增加75% ，癌症死亡率风险增加3至4倍，这与小鼠实验的结果一致。这些研究表明蛋白质和氨基酸、生长激素释放激素-IGF-1/胰岛素、Tor-S6k信号传导、衰老和疾病之间存在保守的联系。
