FOXO1

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Gene Information

Gene Symbol
FOXO1
Aliases
FKH1, FKHR, FOXO1A
HGNC ID
HGNC:3819
NCBI Gene ID
2308
Ensembl Gene ID
ENSG00000150907
Gene Type
protein coding

Genomic Location

Chromosome
13
Assembly
GRCh38
Start Position
40,555,667
End Position
40,667,612
Number of Exons
3
Gene Length
111,946 bp

Overview

A transcription factor of the Fox family, FOXO1 is important in development. It also appears to regulate apoptotic signals.A homologue of FOXO1A, daf-16, has been associated with ageing in roundworms, and overexpression of another homologue, dFOXO, in adult fat body of fruit flies increased longevity in females. Mice overexpressing FOXO1 in skeletal muscle weighed less than controls and had a reduced skeletal muscle mass, suggesting that FOXO1 could play a role in the age-related decline in muscle mass. Results from mice also suggest that FOXO1 could be involved in type 2 diabetes. Although at present there is no evidence directly linking FOXO1 to human ageing, it remains a putative player in the human ageing process.

Research Papers

9 papers in databaseSearch for More Papers
#1
Score:
90%

Deletion of skeletal muscle Akt1/2 causes osteosarcopenia and reduces lifespan in mice.

Nat Commun
2022
PMID: 36198696

Modification Effects

Deletion of Akt1/2 in skeletal muscle; impaired insulin signaling, reduced muscle mass, and motor function impairment

Longevity Association

Reduced lifespan in mice; mechanism: accelerated osteosarcopenia, insulin resistance, and increased susceptibility to debilitation and tumors

#2
Score:
80%

Neuronal C/EBPbeta/AEP pathway shortens life span via selective GABAnergic neuronal degeneration by FOXO repression.

Sci Adv
2022
PMID: 35353567

Modification Effects

C/EBPbeta overexpression; repression of FOXOs, up-regulation of AEP, and selective GABAnergic neuronal degeneration

Longevity Association

Shortened life span in mice and C. elegans; mechanism: aberrant neural excitation, cognitive dysfunction, and repression of longevity-promoting genes (daf-16, FOXO1)

#3
Score:
80%

Regulation of lifespan by neural excitation and REST.

Nature
2019
PMID: 31619788

Modification Effects

Downregulation of genes related to neural excitation and synaptic function; REST upregulation represses excitation-related genes

Longevity Association

Extended longevity in humans; increased longevity in C. elegans through inhibition of neural excitation; mechanism: excitatory-inhibitory balance regulation, activation of FOXO1 and DAF-16 transcription factors

#4
Score:
80%

Impact of visceral adipose tissue on longevity and metabolic health: a comparative study of gene expression in perirenal and epididymal fat of Ames dwarf mice.

Geroscience
2024
PMID: 38517641

Modification Effects

Prop1(df) gene mutation; deficiency in GH, prolactin, and TSH; low circulating IGF-1 levels; altered gene expression in visceral adipose tissue, including upregulation of Lpl, Adrbeta3, Rstn, Foxo1, and others

Longevity Association

Longevity phenotype in Ames dwarf mice; increased insulin sensitivity and metabolic health; mechanism: epigenetic reprogramming of adipose tissue, hormonal changes, and altered gene expression in metabolic regulation, tumor suppression, and mitochondrial biogenesis

#5
Score:
80%

Uterine-specific SIRT1 deficiency confers premature uterine aging and impairs invasion and spacing of blastocyst, and stromal cell decidualization, in mice.

Mol Hum Reprod
2022
PMID: 35536234

Modification Effects

Uterine-specific SIRT1 deficiency; impaired invasion and spacing of blastocysts, and stromal cell decidualization, due to dysregulated estrogen, progesterone, and Indian hedgehog signaling pathways

Longevity Association

Premature uterine aging, subfertility, and sterility by 25.1 weeks of age in mice; mechanism: accelerated cell senescence, perturbations of histone proteins and epigenetic modifiers, and increased deposition of aging-related fibrillar collagens

#6
Score:
80%

Abrogation of Age-Induced MicroRNA-195 Rejuvenates the Senescent Mesenchymal Stem Cells by Reactivating Telomerase.

Stem Cells
2016
PMID: 26390028

Modification Effects

MiR-195 inhibition; increased Tert expression, telomere relengthening, and reduced senescence-associated beta-galactosidase

Longevity Association

Rejuvenation of aged mesenchymal stem cells; improved proliferative abilities, reduced infarction size, and improved LV function in mice; mechanism: telomerase reactivation and increased antiaging factors expression

#7
Score:
80%

IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease.

J Clin Invest
2011
PMID: 21926467

Modification Effects

Irs2 signaling modulation; altered FoxO1 nuclear localization and expression of FoxO1-dependent genes

Longevity Association

Extended life span in R6/2*Irs2+/-*Irs2betatg mice; mechanism: improved autophagy, mitochondrial function, and resistance to oxidative stress

#8
Score:
80%

Prdx6 Plays a Main Role in the Crosstalk Between Aging and Metabolic Sarcopenia.

Antioxidants (Basel)
2020
PMID: 32316601

Modification Effects

Prdx6 knockout; reduced telomere length, impaired IGF-1/Akt-1/mTOR pathway, increased FOXO1 nuclear localization, decreased MyoD levels, and increased MuRF1 levels

Longevity Association

Muscle atrophy, reduced muscle strength, and increased cellular senescence in Prdx6(-/-) mice; mechanism: oxidative stress, impaired redox homeostasis, and activation of p53-p21 pro-aging pathway

#9
Score:
80%

LMNA-related muscular dystrophy involving myoblast proliferation and apoptosis through the FOXO1/GADD45A pathway.

Biochim Biophys Acta Mol Basis Dis
2024
PMID: 37951507

Modification Effects

Lmna-W520R mutation; altered FOXO1/GADD45A pathway activation, increased expression of FOXO1 and GADD45A, decreased H3K27me3 in FOXO1 promoter region

Longevity Association

Shortened lifespan in homozygous mutant mice; mechanism: muscle atrophy through FOXO1/GADD45A pathway, partially rescued by FOXO1 inhibitor with improved motor function and prolonged survival

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