Evidence mapPaperPMID 34197020Full record

ArticleAging cell2021

Genetic signature of human longevity in PKC and NF-κB signaling.

Seungjin Ryu, Jeehae Han, Trina M Norden-Krichmar, Quanwei Zhang, Seunggeun Lee, Zhengdong Zhang, Gil Atzmon, Laura J Niedernhofer, Paul D Robbins, Nir Barzilai and 2 more

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Genes and Longevity of Lifespan.International journal of molecular sciences · 2022
    Review
  14. Article
  15. Article
  16. Review
  17. Article
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

12 authors at 4 institutions in 2 countries.

Seungjin RyuDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID 0000-0001-6353-8789
Jeehae HanDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Trina M Norden-KrichmarThe Scripps Research Institute, La Jolla, CA, USA.ORCID 0000-0002-0199-9915
Quanwei ZhangDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Seunggeun LeeDepartment of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
Zhengdong ZhangDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Gil AtzmonDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Laura J NiedernhoferInsitute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0002-1074-1385
Paul D RobbinsInsitute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.ORCID 0000-0003-1068-7099
Nir BarzilaiDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Nicholas J SchorkThe Scripps Research Institute, La Jolla, CA, USA.
Yousin SuhDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID 0000-0002-9275-6192
Albert Einstein College of Medicine · USScripps Research Institute · USUniversity of Minnesota · USUniversity of Michigan · US

Funding

Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · 2023 to 2025
$9.1M
THE IMPACT OF CELLULAR DEFENSE ON THE ROLE OF Ku80 IN GENOME MAINTENANCE AND LONGP01AG017242 · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · 1999 to 2005
$5.8M
Validation and characterization of the identified variants associated with human longevity in mouse modelsU19AG056278 · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2025 to 2025
$2.6M
A stress-induced promoter pause release program in cardiomyocytes protecting against myocardial infarctionR01HL150521 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MICHAEL G ROSENFELD · 2022 to 2023
$1.3M
Human tissue specific age-related gene expression changes, their genetic regulations and the link to human diseasesR01AG055501 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Zhidong Tu · 2022 to 2022
$371k
NHLBI NIH HHS R01 HL150521NIA NIH HHS P01 AG017242NIA NIH HHS P01 AG062413NIA NIH HHS R01 AG055501NIA NIH HHS R01 AG057433NIA NIH HHS R01 AG057706NIA NIH HHS R01 AG057909NIA NIH HHS R01 AG061521NIA NIH HHS R01 AG069750NIA NIH HHS RF1 AG057341NIA NIH HHS U19 AG056278NIDDK NIH HHS R01 DK127778
6 · The paper itself

Abstract

Gene variants associated with longevity are also associated with protection against cognitive decline, dementia and Alzheimer's disease, suggesting that common physiologic pathways act at the interface of longevity and cognitive function. To test the hypothesis that variants in genes implicated in cognitive function may promote exceptional longevity, we performed a comprehensive 3-stage study to identify functional longevity-associated variants in ~700 candidate genes in up to 450 centenarians and 500 controls by target capture sequencing analysis. We found an enrichment of longevity-associated genes in the nPKC and NF-κB signaling pathways by gene-based association analyses. Functional analysis of the top three gene variants (NFKBIA, CLU, PRKCH) suggests that non-coding variants modulate the expression of cognate genes, thereby reducing signaling through the nPKC and NF-κB. This matches genetic studies in multiple model organisms, suggesting that the evolutionary conservation of reduced PKC and NF-κB signaling pathways in exceptional longevity may include humans.

Indexed as

Genetic VariationHumansLongevityNF-kappa BPeptide FragmentsProtein Kinase CSignal TransductionNF-kappa BPeptide FragmentsProtein Kinase Cprotein kinase C (19-31)centenariangenetic variantlongevityNF-κBPKCrare variant

Identifiers

PMID34197020
PMCPMC8282271
OpenAlexW3176556163

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.