Abstract

The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, FOXO3 expression, and inflammatory cytokine levels in men and women. In agreement with earlier work, the FOXO3 longevity variant conferred protection against telomere shortening of peripheral blood mononuclear cells from adults aged 55 years and older. This was accompanied by higher levels of telomerase activity in mononuclear cells for carriers of the longevity-associated FOXO3 G-allele of SNP rs2802292 (P = 0.015). FOXO3 mRNA expression increased slightly with age in both young (P = 0.02) and old (P = 0.08) G-allele carriers. Older female G-allele carriers displayed a modest decline in levels of pro-inflammatory cytokine IL-6 with age (P = 0.07). In contrast, older male G-allele carriers displayed an age-dependent increase in levels of anti-inflammatory cytokine IL-10 with age (P = 0.04). Thus, FOXO3 may act through several different pro-longevity mechanisms, which may differ by age and sex.

Details

Title
Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans
Author
Torigoe, Trevor H. 1   VIAFID ORCID Logo  ; Willcox, D. Craig 2 ; Shimabukuro, Michio 3   VIAFID ORCID Logo  ; Higa, Moritake 4 ; Gerschenson, Mariana 5 ; Andrukhiv, Anastasia 5 ; Suzuki, Makoto 6 ; Morris, Brian J. 7   VIAFID ORCID Logo  ; Chen, Randi 8 ; Gojanovich, Greg S. 5 ; Allsopp, Richard C. 9 ; Willcox, Bradley J. 10 

1  University of Hawaii, Institute for Biogenesis Research, Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, USA (GRID:grid.162346.4) (ISNI:0000 0001 1482 1895) 
2  University of Hawaii, Department of Geriatric Medicine, John A. Burns School of Medicine, Honolulu, USA (GRID:grid.162346.4) (ISNI:0000 0001 1482 1895); Okinawa International University, Department of Human Welfare, Ginowan, Japan (GRID:grid.443581.f) (ISNI:0000 0000 9609 2261); Okinawa Research Center for Longevity Science, Urasoe, Japan (GRID:grid.443581.f); Kuakini Medical Center, Department of Research, Honolulu, USA (GRID:grid.415514.0) (ISNI:0000 0001 0430 0535) 
3  Fukushima Medical University School of Medicine, Fukushima, Department of Diabetes, Endocrinology and Metabolism, Fukushima, Japan (GRID:grid.411582.b) (ISNI:0000 0001 1017 9540); Tomishiro Central Hospital, Diabetes and Life-Style Related Disease Center, Tomishiro, Japan (GRID:grid.460111.3) 
4  Tomishiro Central Hospital, Diabetes and Life-Style Related Disease Center, Tomishiro, Japan (GRID:grid.460111.3) 
5  University of Hawaii, Department of Cell and Molecular Biology, John A. Burns School of Medicine, Honolulu, USA (GRID:grid.162346.4) (ISNI:0000 0001 1482 1895) 
6  Okinawa Research Center for Longevity Science, Urasoe, Japan (GRID:grid.162346.4) 
7  University of Hawaii, Department of Geriatric Medicine, John A. Burns School of Medicine, Honolulu, USA (GRID:grid.162346.4) (ISNI:0000 0001 1482 1895); Kuakini Medical Center, Department of Research, Honolulu, USA (GRID:grid.415514.0) (ISNI:0000 0001 0430 0535); University of Sydney, School of Medical Sciences, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
8  Kuakini Medical Center, Department of Research, Honolulu, USA (GRID:grid.415514.0) (ISNI:0000 0001 0430 0535) 
9  University of Hawaii, Institute for Biogenesis Research, Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, Honolulu, USA (GRID:grid.162346.4) (ISNI:0000 0001 1482 1895); Okinawa Research Center for Longevity Science, Urasoe, Japan (GRID:grid.162346.4) 
10  University of Hawaii, Department of Geriatric Medicine, John A. Burns School of Medicine, Honolulu, USA (GRID:grid.162346.4) (ISNI:0000 0001 1482 1895); Okinawa Research Center for Longevity Science, Urasoe, Japan (GRID:grid.162346.4); Kuakini Medical Center, Department of Research, Honolulu, USA (GRID:grid.415514.0) (ISNI:0000 0001 0430 0535) 
Pages
18
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20563973
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41514-024-00142-8
ProQuest document ID
2952138871
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.