Evidence map›Paper›PMID 37561089›Full record

ArticleAmerican journal of hypertension2023

Genes That Extend Lifespan May Do So by Mitigating the Increased Risk of Death Posed by Having Hypertension.

Brian J Morris, Timothy A Donlon

Open access · hybridAbstract read
In one paragraph

Article in American journal of hypertension, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 57% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Brian J MorrisDepartment of Research, NIH Center of Biomedical Research Excellence on Aging, Kuakini Medical Center, Honolulu, Hawaii 96817, USA.
Timothy A DonlonDepartment of Research, NIH Center of Biomedical Research Excellence on Aging, Kuakini Medical Center, Honolulu, Hawaii 96817, USA.
Kuakini Medical Center · USUniversity of Sydney · AU

Funding

Epidemiology of Brain Aging in the Very OldU01AG019349 · NIA · KUAKINI MEDICAL CENTER · PI WHITE, LON RAY · 2001 to 2011
$14.0M
Productive and Leisure Activities and Cognition in Later LifeP20GM125526 · NIGMS · KUAKINI MEDICAL CENTER · PI LEE, YEONJUNG · 2019 to 2023
$12.0M
FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III. Administrative Supplement.R01AG027060 · NIA · KUAKINI MEDICAL CENTER · PI Gregory J. Tranah, BRADLEY JOHN WILLCOX · 2005 to 2026
$8.1M
Energy-sensing Pathways, Healthy Aging and LongevityR01AG038707 · NIA · KUAKINI MEDICAL CENTER · PI WILLCOX, BRADLEY JOHN · 2011 to 2014
$1.4M
HONOLULU ASIA AGING STUDYN01AG042149 · NIA · KUAKINI MEDICAL CENTER · PI FOLEY, DANIEL · 1994 to 2000
$1.1M
HONOLULU HEART PROGRAMN01HC005102 · HC · KUAKINI MEDICAL CENTER · PI CURB, JESS DAVID · 1990 to 1997
–
NHLBI NIH HHS N01 HC005102NHLBI NIH HHS N01-HC-05102NIA NIH HHS R01 AG027060NIA NIH HHS R01 AG038707NIA NIH HHS U01 AG019349NIGMS NIH HHS P20 GM125526NIH HHS N01-AG-4-2149
6 · The paper itself

Abstract

backgroundGenetic factors influence lifespan. In humans, there appears to be a particularly strong genetic effect in those aged ≥ 90 years. An important contribution is nutrient sensing genes which confer cell resilience.

methodsOur research has been investigating the genetic factors by longitudinal studies of American men of Japanese descent living on the island of Oahu in Hawaii. This cohort began as the Honolulu Heart Program in the mid-1960s and most subjects are now deceased.

resultsWe previously discovered various genes containing polymorphisms associated with longevity. In recent investigations of the mechanism involved we found that the longevity genotypes ameliorated the risk of mortality posed by having a cardiometabolic disease (CMD)-most prominently hypertension. For the gene FOXO3 the protective alleles mitigated the risk of hypertension, coronary heart disease (CHD) and diabetes. For the kinase MAP3K5 it was hypertension, CHD and diabetes, for the kinase receptor PIK3R1 hypertension, CHD and stroke, and for the growth hormone receptor gene (GHR) and vascular endothelial growth factor receptor 1 gene (FLT1), it was nullifying the higher mortality risk posed by hypertension. Subjects with a CMD who had a longevity genotype had similar survival as men without CMD. No variant protected against risk of death from cancer. We have postulated that the longevity-associated genotypes reduced mortality risk by effects on intracellular resilience mechanisms. In a proteomics study, 43 "stress" proteins and associated biological pathways were found to influence the association of FOXO3 genotype with reduced mortality.

conclusionsOur landmark findings indicate how heritable genetic components affect longevity.

Indexed as

Coronary DiseaseDiabetes MellitusHypertensionHumansLongevityMaleRisk FactorsVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Ablood pressureFLT1FOXO3geneticsGHRhypertensionlifespanMAP3K5mortalityPIK3R1resilience

Identifiers

PMID37561089
PMCPMC10647014
OpenAlexW4385715509

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Registered trials

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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.