Acarbose improves health and lifespan in aging HET3 mice
Acarbose improves health and lifespan in aging HET3 mice
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DOI：
10.1111/acel.12898
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发表时间：
2019-04-01
期刊：
影响因子：
7.8
通讯作者：
Miller, Richard A.
中科院分区：
文献类型：
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作者：
Harrison, David E.;Strong, Randy;Miller, Richard A.
在我们之前的报告中，阿卡波糖（ACA）是一种阻断餐后血糖峰值的药物，可以延长小鼠的寿命，我们研究了三种剂量的ACA: 400ppm、1000 ppm（原始剂量）和2500 ppm，在三个位点使用遗传异质性小鼠。每次剂量在两性中都导致显著变化（log-rank检验），对男性的影响更大，与原始报告一致。三种剂量间无显著差异。两种较高剂量的疫苗使男性的平均寿命增加了16%或17%，而女性只增加了4%或5%。在每次剂量下，男性第90百分位年龄显著增加（8%-11%），但仅在1000ppm剂量下，女性第90百分位年龄显著增加（3%）。性别对寿命的影响不能简单地用体重或脂肪量来解释，因为ACA对女性的影响大于男性。1000ppm浓度的ACA减少了男性的肺肿瘤，减少了两性的肝脏变性和女性的肾小球硬化，降低了男性再喂养时的血糖反应，并改善了老年女性的旋转棒性能，但没有改善男性。还测试了其他三种干预措施：熊果酸、2-（2-羟基苯基）苯并噻唑（HBX）和INT-767；在测试剂量下，这些都不影响寿命。阿卡波糖的结果证实并扩展了我们的原始报告，促使人们进一步关注短暂的高血糖对衰老和衰老疾病（包括癌症）的影响，并应激发阿卡波糖和其他人类血糖控制药物的研究。
To follow-up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log-rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%-11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole (HBX), and INT-767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose-control drugs in humans.