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Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used

Harrison, David E., Strong, Randy, Reifsnyder, Peter, Rosenthal, Nadia, Korstanje, Ron, Fernandez, Elizabeth, Flurkey, Kevin, Ginsburg, Brett C., Murrell, Meredith D., Javors, Martin A., Lopez-Cruzan, Marisa, Nelson, James F., Willcox, Bradley J., Allsopp, Richard, Watumull, David M., Watumull, David G., Cortopassi, Gino, Kirkland, James L., Tchkonia, Tamar, Choi, Young Geun, Yousefzadeh, Matthew J., Robbins, Paul D., Mitchell, James R., Acar, Murat, Sarnoski, Ethan A., Bene, Michael R., Salmon, Adam, Kumar, Navasuja, Miller, Richard A.·2023·GeroScience
DOI 10.1007/s11357-023-01011-0PMC PMC10828146
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Abstract

In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang–Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.

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Metadata

Authors
Harrison, D. E., Strong, R., Reifsnyder, P., Rosenthal, N., Korstanje, R., Fernandez, E., Flurkey, K., Ginsburg, B. C., Murrell, M. D., Javors, M. A., Lopez-Cruzan, M., Nelson, J. F., Willcox, B. J., Allsopp, R., Watumull, D. M., Watumull, D. G., Cortopassi, G., Kirkland, J. L., Tchkonia, T., Choi, Y. G., Yousefzadeh, M. J., Robbins, P. D., Mitchell, J. R., Acar, M., Sarnoski, E. A., Bene, M. R., Salmon, A., Kumar, N., & Miller, R. A.
Venue
GeroScience
Publisher
Springer Science and Business Media LLC
Published
2023-12-02
Volume
46
Issue
1
Pages
795-816
ISSN
2509-2723
DOI
10.1007/s11357-023-01011-0
PMC
PMC10828146
Cited by
56
References
6
Language
en
Licence
Funders
  • National Institute on Aging (AG022308, AG022303, AG022307, AG013319)
  • National Cancer Institute (CA034196)
  • Glenn Foundation for Medical Research
  • U.S. Department of Veterans Affairs

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