Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice

Randy Strong, Richard A. Miller, Clinton M. Astle, Robert A. Floyd, Kevin Flurkey, Kenneth L. Hensley, Martin A. Javors, Christiaan Leeuwenburgh, James F. Nelson, Ennio Ongini, Nancy L. Nadon, Huber R. Warner, David E. Harrison

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-α-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA (p = 0.12) nor aspirin (p = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice.

Original languageEnglish (US)
Pages (from-to)641-650
Number of pages10
JournalAging cell
Volume7
Issue number5
DOIs
StatePublished - 2008

Keywords

  • Aging
  • Aspirin
  • Longevity
  • Mice
  • Nordihydroguaiaretic acid

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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