ArticlePLoS biology2006
Lipoprotein genotype and conserved pathway for exceptional longevity in humans.
Article in PLoS biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled it.
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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.
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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.
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Who cites it
108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- Pleiotropic Associations of Allelic Variants in a 2q22 Region with Risks of Major Human Diseases and Mortality.PLoS genetics · 2016Pooled it
- A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.The journals of gerontology. Series A, Biological sciences and medical sciences · 2010Pooled it
- Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing.Mechanisms of ageing and development · 2013Trial
- Blood-based biomarkers in centenarians and non-centenarians: a matched, population-based retrospective cohort study using primary care records in Catalonia, Spain.Biogerontology · 2025Article
- Factors involved in human healthy aging: insights from longevity individuals.Frontiers of medicine · 2025Review
- Identification of functional rare coding variants in IGF-1 gene in humans with exceptional longevity.Scientific reports · 2025Article
- Identification of functional rare coding variants in IGF-1 gene in humans with exceptional longevity.bioRxiv : the preprint server for biology · 2024Article
- Review
- Discovering Biological Mechanisms of Exceptional Human Health Span and Life Span.Cold Spring Harbor perspectives in medicine · 2023Review
- Particle Nanoarchitectonics for Nanomedicine and Nanotherapeutic Drugs with Special Emphasis on Nasal Drugs and Aging.Biomedicines · 2023Review
- Review
- Extending human healthspan and longevity: a symposium report.Annals of the New York Academy of Sciences · 2022Article
- Low Risk for Developing Diabetes Among the Offspring of Individuals With Exceptional Longevity and Their Spouses.Frontiers in clinical diabetes and healthcare · 2022Article
- Are Alzheimer's and coronary artery diseases genetically related to longevity?Frontiers in psychiatry · 2022Article
- HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: A Multicenter Cohort Study.The Journal of clinical endocrinology and metabolism · 2021Article
- β-Cell Dysfunction, Hepatic Lipid Metabolism, and Cardiovascular Health in Type 2 Diabetes: New Directions of Research and Novel Therapeutic Strategies.Biomedicines · 2021Review
- Apolipoprotein CIII Is an Important Piece in the Type-1 Diabetes Jigsaw Puzzle.International journal of molecular sciences · 2021Review
- Genetic Regulatory Networks of Apolipoproteins and Associated Medical Risks.Frontiers in cardiovascular medicine · 2021Review
- Targeting metabolic pathways for extension of lifespan and healthspan across multiple species.Ageing research reviews · 2020Review
- Identification and genomic analysis of pedigrees with exceptional longevity identifies candidate rare variants.Neurobiology of disease · 2020Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Alteration of single genes involved in nutrient and lipoprotein metabolism increases longevity in several animal models. Because exceptional longevity in humans is familial, it is likely that polymorphisms in genes favorably influence certain phenotypes and increase the likelihood of exceptional longevity. A group of Ashkenazi Jewish centenarians (n = 213), their offspring (n = 216), and an age-matched Ashkenazi control group (n = 258) were genotyped for 66 polymorphisms in 36 candidate genes related to cardiovascular disease (CVD). These genes were tested for association with serum lipoprotein levels and particle sizes, apolipoprotein A1, B, and C-3 levels and with outcomes of hypertension, insulin resistance, and mortality. The prevalence of homozygosity for the -641C allele in the APOC3 promoter (rs2542052) was higher in centenarians (25%) and their offspring (20%) than in controls (10%) (p = 0.0001 and p = 0.001, respectively). This genotype was associated with significantly lower serum levels of APOC3 and a favorable pattern of lipoprotein levels and sizes. We found a lower prevalence of hypertension and greater insulin sensitivity in the -641C homozygotes, suggesting a protective effect against CVD and the metabolic syndrome. Finally, in a prospectively studied cohort, a significant survival advantage was demonstrated in those with the favorable -641C homozygote (p < 0.0001). Homozygosity for the APOC3 -641C allele is associated with a favorable lipoprotein profile, cardiovascular health, insulin sensitivity, and longevity. Because modulation of lipoproteins is also seen in genetically altered longevity models, it may be a common pathway influencing lifespan from nematodes to humans.
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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.