ReviewTrends in neurosciences2014
Exercise, APOE genotype, and the evolution of the human lifespan.
Review in Trends in neurosciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 3 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
71 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Taste receptor polymorphisms and longevity: a systematic review and meta-analysis.Aging clinical and experimental research · 2021Pooled it
- Do exercise-associated genes explain phenotypic variance in the three components of fitness? a systematic review & meta-analysis.PloS one · 2021Pooled it
- A Meta-Analysis of Studies of the Effect of Mind Body Exercise on Various Domains of Cognitive Function in Older People With or Without Mild Cognitive Impairment.Journal of evidence-based integrative medicinePooled it
- Effect of aerobic exercise on cognition in younger adults: A randomized clinical trial.Neurology · 2019Trial
- Divergent biological consequences of APOE isoforms across industrialized and non-industrial environments.PLoS genetics · 2026Article
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- Canine Cognitive Dysfunction and Alzheimer's Disease: Pathophysiological Relationships and the Impact of Glymphatic System Impairment on Neurodegeneration.Veterinary sciences · 2026Review
- Divergent Biological Consequences of APOE Isoforms Across Industrialized and Non-Industrial Environments.bioRxiv : the preprint server for biology · 2026Article
- Structural and functional alterations of posterior cingulate cortex subregions in successful cognitive aging.Frontiers in aging neuroscience · 2026Article
- Human Apolipoprotein E ε4 Allele Modulates Energy Substrate Availability, Seizure Burden, Mortality and Hippocampal Injury, Cell Death, and Inflammation after Neonatal Hypoxic-Ischemic Brain Injury.Developmental neuroscience · 2026Article
- Alzheimer Syndrome or Age-Related Dementia-History, Therapy and Prevention.Journal of clinical medicine · 2025Article
- Pluripotent Cells Expressing APOE4 Exhibit a Pronounced Pro-Apoptotic Phenotype Accompanied by Markers of Hyperinflammation and a Blunted NF-κB Response.International journal of molecular sciences · 2025Article
- Article
- Regional network covariance patterns of white matter integrity related to cardiorespiratory fitness in healthy aging.Frontiers in aging neuroscience · 2025Article
- Article
- Impact of age and apolipoprotein E ε4 status on regional white matter hyperintensity volume and cognition in healthy aging.Journal of the International Neuropsychological Society : JINS · 2024Article
- Oxygen and the Spark of Human Brain Evolution: Complex Interactions of Metabolism and Cortical Expansion across Development and Evolution.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Article
- Current allele distribution of the human longevity gene APOE in Europe can mainly be explained by ancient admixture.Aging cell · 2023Article
- APOE ɛ4 allele and TOMM40-APOC1 variants jointly contribute to survival to older ages.Aging cell · 2022Article
- Cardiorespiratory fitness decreases the odds for subclinical carotid plaques in apolipoprotein e4 homozygotes.Scientific reports · 2022Article
11 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
2 authors.
Funding
Abstract
Humans have exceptionally long lifespans compared with other mammals. However, our longevity evolved when our ancestors had two copies of the apolipoprotein E (APOE) ɛ4 allele, a genotype that leads to a high risk of Alzheimer's disease (AD), cardiovascular disease, and increased mortality. How did human aging evolve within this genetic constraint? Drawing from neuroscience, anthropology, and brain-imaging research, we propose the hypothesis that the evolution of increased physical activity approximately 2 million years ago served to reduce the amyloid plaque and vascular burden of APOE ɛ4, relaxing genetic constraints on aging. This multidisciplinary approach links human evolution with health and provides a complementary perspective on aging and neurodegenerative disease that may help identify key mechanisms and targets for intervention.
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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.