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

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)795-816
Number of pages22
JournalGeroScience
Volume46
Issue number1
DOIs
StatePublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • 4-Phenylbutyrate (PBA)
  • Astaxanthin (Asta)
  • Dimethyl Fumarate (DMF)
  • Fisetin (Fis)
  • Heterogeneous mice
  • Lifespan
  • Meclizine (Mec)
  • Mycophenolic acid (MPA)
  • SG1002

PubMed: MeSH publication types

  • Journal Article

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