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.

Autor: Harrison DE; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA. david.harrison@jax.org., Strong R; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA.; Education, and Clinical Center, Geriatric Research, San Antonio, TX, USA.; Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA.; Department of Pharmacology, The University of Texas Health Science Center, San Antonio, TX, USA., Reifsnyder P; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA., Rosenthal N; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA., Korstanje R; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA., Fernandez E; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA.; Education, and Clinical Center, Geriatric Research, San Antonio, TX, USA.; Department of Pharmacology, The University of Texas Health Science Center, San Antonio, TX, USA., Flurkey K; The Jackson Laboratory, 600 Main Street, Bar Harbor, ME, 04609, USA., Ginsburg BC; Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA., Murrell MD; Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA., Javors MA; Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA., Lopez-Cruzan M; Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, USA., Nelson JF; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA.; Department of Physiology, The University of Texas Health Sciences Center, San Antonio, TX, USA., Willcox BJ; John A. Burns School of Medicine, University of Hawai'I at Mānoa, Honolulu, HI, USA., Allsopp R; John A. Burns School of Medicine, University of Hawai'I at Mānoa, Honolulu, HI, USA., Watumull DM; Cardax, Honolulu, HI, USA.; AX3 Life, Honolulu, HI, USA., Watumull DG; Cardax, Honolulu, HI, USA.; AX3 Life, Honolulu, HI, USA., Cortopassi G; Department of Molecular Biosciences, University of California, Davis, CA, USA., Kirkland JL; Mayo Clinic, Rochester, MN, USA., Tchkonia T; Mayo Clinic, Rochester, MN, USA., Choi YG; University of Minnesota, Minneapolis, MN, USA., Yousefzadeh MJ; University of Minnesota, Minneapolis, MN, USA., Robbins PD; University of Minnesota, Minneapolis, MN, USA., Mitchell JR; Harvard School of Public Health, Boston, MA, USA., Acar M; Department of Basic Medical Sciences, School of Medicine, Koç University, 34450, Istanbul, Turkey., Sarnoski EA; Department of Internal Medicine, Yale University, New Haven, CT, USA., Bene MR; Department of Molecular Medicine, The University of Texas Health Sciences Center, San Antonio, TX, USA., Salmon A; Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, TX, USA.; Education, and Clinical Center, Geriatric Research, San Antonio, TX, USA.; Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA.; Department of Molecular Medicine, The University of Texas Health Sciences Center, San Antonio, TX, USA., Kumar N; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA., Miller RA; Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Feb; Vol. 46 (1), pp. 795-816. Date of Electronic Publication: 2023 Dec 02.
DOI: 10.1007/s11357-023-01011-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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