Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.
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-alpha-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 life span 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.
Strong
Randy
R
Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX 78229, USA. strong@uthscsa.edu
Miller
Richard A
RA
Astle
Clinton M
CM
Floyd
Robert A
RA
Flurkey
Kevin
K
Hensley
Kenneth L
KL
Javors
Martin A
MA
Leeuwenburgh
Christiaan
C
Nelson
James F
JF
Ongini
Ennio
E
Nadon
Nancy L
NL
Warner
Huber R
HR
Harrison
David E
DE
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000097:blood; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000031:analogs & derivatives; D016166:Free Radical Scavengers / Q000008:administration & dosage; D018740:Genetic Heterogeneity / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000008:administration & dosage; D008136:Longevity / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D009637:Masoprocol / Q000008:administration & dosage* / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011897:Random Allocation; D012727:Sex Characteristics; D016019:Survival Analysis
D003497:Cyclic N-Oxides; D016861:Cyclooxygenase Inhibitors; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; C095631:nitroflurbiprofen; C029217:phenyl-N-tert-butylnitrone; D005480:Flurbiprofen; D009637:Masoprocol; D001241:Aspirin