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Aging Cell. 2019 Apr;18(2):e12898. doi: 10.1111/acel.12898. Epub 2019 Jan 27.

Acarbose improves health and lifespan in aging HET3 mice.

Author information

1
The Jackson Laboratory, Bar Harbor, Maine.
2
Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
3
Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas.
4
Research Service, South Texas Veterans Health Care System, San Antonio, Texas.
5
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
6
Buck Institute for Research on Aging, Novato, California.
7
Metropolitan Autonomous University, Lerma, Mexico.
8
University of Texas at Austin, Austin, Texas.
9
Department of Pathology, University of Michigan, Ann Arbor, Michigan.
10
Geriatrics Center, University of Michigan, Ann Arbor, Michigan.
11
Department of Epidemiology & Biostatistics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
12
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
13
Georgetown University, Washington, District of Columbia.
14
Division of Aging Biology, National Institute on Aging, Bethesda, Maryland.
15
Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
16
Unit for Laboratory Animal Medicine and Department of Pathology, University of Michigan, Ann Arbor, Michigan.

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.

KEYWORDS:

acarbose; health measures; heterogeneous mice; lifespan

PMID:
30688027
DOI:
10.1111/acel.12898
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