ReviewGerontology2015
FOXO3: A Major Gene for Human Longevity--A Mini-Review.
Review in Gerontology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
195 citing papers in PubMed, 2 syntheses or guidelines pooled it, 339 citations in OpenAlex.
- Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Pooled it
- Association Analysis of FOXO3 Longevity Variants With Blood Pressure and Essential Hypertension.American journal of hypertension · 2016Pooled it
- Sensory decline in aging and neurodegeneration: A mitochondrial perspective.Pharmacological research · 2026Review
- Single-cell profiling of DNA methylation in autism spectrum disorder prefrontal cortex reveals distinct regulatory and aging signatures.Cell genomics · 2026Article
- FOXO4 as a Redox-Sensitive Regulator of Antioxidant Defense and Cellular Senescence: Cysteine-Based Signaling, p53 Interaction, and Therapeutic Targeting.Antioxidants (Basel, Switzerland) · 2026Review
- Renoprotective effects of perampanel against cisplatin-induced acute kidney injury: managing NLRP3-pyroptosis and enhancement of antioxidant defense.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling.Science advances · 2026Article
- Vascular Aging.Circulation · 2026Review
- Pleiotropy and disease interactors: the dual nature of genes linking ageing and ageing-related diseases.Biogerontology · 2026Article
- Genome-wide association study and pathway analysis of healthy aging in Super Seniors.GeroScience · 2026Article
- Age-stratified genomic analyses reveal population-specific genetic determinants of exceptional longevity in Taiwan.GeroScience · 2026Article
- A unified therapeutic theory for treating cancer via master regulators of the universal apoptosis network.Cell death discovery · 2026Review
- Plasma Proteome Profiling of Centenarian Across Switzerland Reveals Key Youth-Associated Proteins.Aging cell · 2026Article
- Plasma proteomics identify novel biomarkers and dynamic patterns of biological aging.Journal of advanced research · 2026Article
- Therapeutic Targeting of Viral Myocarditis with Natural Products and Herbal Medicines: From Immune-Inflammatory Mechanisms to Clinical Translation.Journal of inflammation research · 2026Review
- CircAFF3 modulation of p53-ID2 signaling in the retinal pigment epithelium links inflammation with cell death in dry age-related macular degeneration.Frontiers in cell and developmental biology · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- Grip strength as a systems biomarker of aging: neuromuscular junction constraints and biomarker decoupling in gene therapy.Frontiers in aging · 2026Article
- Exercise suppresses DEAF1 to normalize mTORC1 activity and reverse muscle aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The drug discovery and therapeutic nano-strategies targeting cellular senescence.Materials today. Bio · 2025Review
135 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundThe gene FOXO3, encoding the transcription factor forkhead box O-3 (FoxO3), is one of only two for which genetic polymorphisms have exhibited consistent associations with longevity in diverse human populations.
objectiveHere, we review the multitude of actions of FoxO3 that are relevant to health, and thus healthy ageing and longevity.
methodsThe study involved a literature search for articles retrieved from PubMed using FoxO3 as keyword.
resultsWe review the molecular genetics of FOXO3 in longevity, then current knowledge of FoxO3 function relevant to ageing and lifespan. We describe how FoxOs are involved in energy metabolism, oxidative stress, proteostasis, apoptosis, cell cycle regulation, metabolic processes, immunity, inflammation and stem cell maintenance. The single FoxO in Hydra confers immortality to this fresh water polyp, but as more complex organisms evolved, this role has been usurped by the need for FoxO to control a broader range of specialized pathways across a wide spectrum of tissues assisted by the advent of as many as 4 FoxO subtypes in mammals. The major themes of FoxO3 are similar, but not identical, to other FoxOs and include regulation of cellular homeostasis, particularly of stem cells, and of inflammation, which is a common theme of age-related diseases. Other functions concern metabolism, cell cycle arrest, apoptosis, destruction of potentially damaging reactive oxygen species and proteostasis.
conclusionsThe mechanism by which longevity-associated alleles of FOXO3 reduce age-related mortality is currently of great clinical interest. The prospect of optimizing FoxO3 activity in humans to increase lifespan and reduce age-related diseases represents an exciting avenue of clinical investigation. Research strategies directed at developing therapeutic agents that target FoxO3, its gene and proteins in the pathway(s) FoxO3 regulates should be encouraged and supported.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.