Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age
Preservation of blood glucose homeostasis in slow-senescing somatotrophism-deficient mice subjected to intermittent fasting begun at middle or old age
复制标题
DOI：
10.1007/s11357-014-9651-2
复制
发表时间：
2014-06-01
期刊：
影响因子：
--
通讯作者：
Bartke, Andrzej
中科院分区：
文献类型：
--
作者：
Arum, Oge;Saleh, Jamal K.;Bartke, Andrzej
血糖稳态调节不良是常见的，后果严重，成本高的老年人和老年人群，导致多营养不良的临床结果。营养信号缺乏和饮食限制都被证明可以延缓衰老的速度，导致有益健康的表型，如存活率增加。使用两个生长激素（GH）信号相关的，缓慢衰老的小鼠突变体，我们测试，通过纵向分析，是否遗传扰动，增加生存也提高衰老的哺乳动物的血糖稳态调节。此外，我们建立了一个饮食限制的范例，也减缓衰老，间歇性禁食（IF）喂养时间表，作为一个短期或持续的干预开始于中年或老年，并评估其对血糖控制的影响。我们发现，GH信号的两种遗传改变中的任何一种都能改善空腹高血糖;此外，两种长寿诱导的生长激素突变都能改善胰岛素敏感性。引人注目的是，我们观察到的主要和广泛的改善血糖稳态控制的IF：IF改善随意喂养的高血糖症，葡萄糖耐量，胰岛素敏感性，并减少肝硬化，在老化突变和正常小鼠。这些关于纠正衰老导致的血糖失调的结果对我们不断老龄化的全球人口具有潜在的重要临床和公共卫生意义，并且与长寿红利概念一致。
Poor blood glucose homeostatic regulation is common, consequential, and costly for older and elderly populations, resulting in pleiotrophically adverse clinical outcomes. Somatotrophic signaling deficiency and dietary restriction have each been shown to delay the rate of senescence, resulting in salubrious phenotypes such as increased survivorship. Using two growth hormone (GH) signaling-related, slow-aging mouse mutants we tested, via longitudinal analyses, whether genetic perturbations that increase survivorship also improve blood glucose homeostatic regulation in senescing mammals. Furthermore, we institute a dietary restriction paradigm that also decelerates aging, an intermittent fasting (IF) feeding schedule, as either a short-term or a sustained intervention beginning at either middle or old age, and assess its effects on blood glucose control. We find that either of the two genetic alterations in GH signaling ameliorates fasting hyperglycemia; additionally, both longevity-inducing somatotrophic mutations improve insulin sensitivity into old age. Strikingly, we observe major and broad improvements in blood glucose homeostatic control by IF: IF improves ad libitum-fed hyperglycemia, glucose tolerance, and insulin sensitivity, and reduces hepatic gluconeogenesis, in aging mutant and normal mice. These results on correction of aging-resultant blood glucose dysregulation have potentially important clinical and public health implications for our ever-graying global population, and are consistent with the Longevity Dividend concept.