Evidence map›Paper›PMID 34436732›Full record

ArticleGeroScience2022

Extreme longevity variants at the FOXO3 locus may moderate FOXO3 isoform levels.

Ryan Frankum, Tom S O Jameson, Bridget A Knight, Francis B Stephens, Benjamin T Wall, Timothy A Donlon, Trevor Torigoe, Bradley J Willcox, D Craig Willcox, Richard C Allsopp and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in GeroScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. [Role and mechanisms of FoxO3a-related signaling pathways in breast cancer cell apoptosis].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review
  3. Article
  4. The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 3 countries.

Ryan FrankumInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter, EX2 5DW, UK.
Tom S O JamesonCollege of Life and Environmental Sciences, University of Exeter, Exeter, UK.
Bridget A KnightNIHR Exeter Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Francis B StephensCollege of Life and Environmental Sciences, University of Exeter, Exeter, UK.
Benjamin T WallCollege of Life and Environmental Sciences, University of Exeter, Exeter, UK.
Timothy A DonlonHonolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Department of Research, Kuakini Medical Center, Honolulu, HI, 96817, USA.
Trevor TorigoeInstitute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
Bradley J WillcoxDepartment of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96817, USA.
D Craig WillcoxInstitute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
Richard C AllsoppInstitute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
Lorna W HarriesInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Barrack Road, Exeter, EX2 5DW, UK. L.W.Harries@exeter.ac.uk.
University of Exeter · GBBiogen (United States) · USOkinawa International University · JPRoyal Devon & Exeter NHS Foundation Trust · GBUniversity of Hawaiʻi at Mānoa · USUniversity of Hawaii System · US

Funding

HONOLULU ASIA AGING STUDYN01AG042149 · NIA · KUAKINI MEDICAL CENTER · PI FOLEY, DANIEL · 1994 to 2000
$1.1M
NIH HHS N01-AG-4-2149
6 · The paper itself

Abstract

The rs2802292, rs2764264 and rs13217795 variants of FOXO3 have been associated with extreme longevity in multiple human populations, but the mechanisms underpinning this remain unclear. We aimed to characterise potential effects of longevity-associated variation on the expression and mRNA processing of the FOXO3 gene. We performed a comprehensive assessment of FOXO3 isoform usage across a wide variety of human tissues and carried out a bioinformatic analysis of the potential for longevity-associated variants to disrupt regulatory regions involved in isoform choice. We then related the expression of full length and 5' truncated FOXO3 isoforms to rs13217795 genotype in peripheral blood and skeletal muscle from individuals of different rs13217795 genotypes. FOXO3 isoforms displayed considerable tissue specificity. We determined that rs13231195 and its tightly aligned proxy variant rs9400239 may lie in regulatory regions involved in isoform choice. The longevity allele at rs13217795 was associated with increased levels of full length FOXO3 isoforms in peripheral blood and a decrease in truncated FOXO3 isoforms in skeletal muscle RNA. We suggest that the longevity effect of FOXO3 SNPs may in part derive from a shift in isoform usage in skeletal muscle away from the production of 5' truncated FOXO3 isoforms lacking a complete forkhead DNA binding domain, which may have compromised functionality.

Indexed as

LongevityPolymorphism, Single NucleotideAllelesForkhead Box Protein O3HumansProtein IsoformsForkhead Box Protein O3FOXO3 protein, humanProtein IsoformsFOXO3HumanIsoformsLongevityVariation

Identifiers

PMID34436732
PMCPMC9135902
OpenAlexW3196241800

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.