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Acarbose improves health and lifespan in aging HET3 mice.

ABSTRACT: 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.

SUBMITTER: Harrison DE

PROVIDER: S-EPMC6413665 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Acarbose improves health and lifespan in aging HET3 mice.

Harrison David E DE Strong Randy R Alavez Silvestre S Astle Clinton Michael CM DiGiovanni John J Fernandez Elizabeth E Flurkey Kevin K Garratt Michael M Gelfond Jonathan A L JAL Javors Martin A MA Levi Moshe M Lithgow Gordon J GJ Macchiarini Francesca F Nelson James F JF Sukoff Rizzo Stacey J SJ Slaga Thomas J TJ Stearns Tim T Wilkinson John Erby JE Miller Richard A RA

Aging cell 20190127 2

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 1 ...[more]

PMID: 30688027

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Dataset Information

Acarbose improves health and lifespan in aging HET3 mice.

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Acarbose improves health and lifespan in aging HET3 mice.

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