Acarbose improves health and lifespan in aging HET3 mice

David E. Harrison, Randy Strong, Silvestre Alavez, Clinton Michael Astle, John DiGiovanni, Elizabeth Fernandez, Kevin Flurkey, Michael Garratt, Jonathan A.L. Gelfond, Martin A. Javors, Moshe Levi, Gordon J. Lithgow, Francesca Macchiarini, James F. Nelson, Stacey J. Sukoff Rizzo, Thomas J. Slaga, Tim Stearns, John Erby Wilkinson, Richard A. Miller

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article numbere12898
JournalAging Cell
Volume18
Issue number2
DOIs
StatePublished - Apr 1 2019

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Acarbose
Health
Blood Glucose
Glucose
Drug and Narcotic Control
Neoplasms
Fats
Weights and Measures
Lung
Liver

Keywords

  • acarbose
  • health measures
  • heterogeneous mice
  • lifespan

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Harrison, D. E., Strong, R., Alavez, S., Astle, C. M., DiGiovanni, J., Fernandez, E., ... Miller, R. A. (2019). Acarbose improves health and lifespan in aging HET3 mice. Aging Cell, 18(2), [e12898]. https://doi.org/10.1111/acel.12898

Acarbose improves health and lifespan in aging HET3 mice. / Harrison, David E.; Strong, Randy; Alavez, Silvestre; Astle, Clinton Michael; DiGiovanni, John; Fernandez, Elizabeth; Flurkey, Kevin; Garratt, Michael; Gelfond, Jonathan A.L.; Javors, Martin A.; Levi, Moshe; Lithgow, Gordon J.; Macchiarini, Francesca; Nelson, James F.; Sukoff Rizzo, Stacey J.; Slaga, Thomas J.; Stearns, Tim; Wilkinson, John Erby; Miller, Richard A.

In: Aging Cell, Vol. 18, No. 2, e12898, 01.04.2019.

Research output: Contribution to journalArticle

Harrison, DE, Strong, R, Alavez, S, Astle, CM, DiGiovanni, J, Fernandez, E, Flurkey, K, Garratt, M, Gelfond, JAL, Javors, MA, Levi, M, Lithgow, GJ, Macchiarini, F, Nelson, JF, Sukoff Rizzo, SJ, Slaga, TJ, Stearns, T, Wilkinson, JE & Miller, RA 2019, 'Acarbose improves health and lifespan in aging HET3 mice', Aging Cell, vol. 18, no. 2, e12898. https://doi.org/10.1111/acel.12898
Harrison DE, Strong R, Alavez S, Astle CM, DiGiovanni J, Fernandez E et al. Acarbose improves health and lifespan in aging HET3 mice. Aging Cell. 2019 Apr 1;18(2). e12898. https://doi.org/10.1111/acel.12898
Harrison, David E. ; Strong, Randy ; Alavez, Silvestre ; Astle, Clinton Michael ; DiGiovanni, John ; Fernandez, Elizabeth ; Flurkey, Kevin ; Garratt, Michael ; Gelfond, Jonathan A.L. ; Javors, Martin A. ; Levi, Moshe ; Lithgow, Gordon J. ; Macchiarini, Francesca ; Nelson, James F. ; Sukoff Rizzo, Stacey J. ; Slaga, Thomas J. ; Stearns, Tim ; Wilkinson, John Erby ; Miller, Richard A. / Acarbose improves health and lifespan in aging HET3 mice. In: Aging Cell. 2019 ; Vol. 18, No. 2.
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