Evidence map›Paper›PMID 24916111›Full record

ArticleCirculation research2014

Metabolic dysfunction consistent with premature aging results from deletion of Pim kinases.

Shabana Din, Mathias H Konstandin, Bevan Johnson, Jacqueline Emathinger, Mirko Völkers, Haruhiro Toko, Brett Collins, Lucy Ormachea, Kaitlen Samse, Dieter A Kubli and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Pim Kinases: Important Regulators of Cardiovascular Disease.International journal of molecular sciences · 2023
    Review
  12. Review
  13. Article
  14. Advances in Human Mitochondria-Based Therapies.International journal of molecular sciences · 2022
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

15 authors at 2 institutions in 1 country.

Shabana DinFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Mathias H KonstandinFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Bevan JohnsonFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Jacqueline EmathingerFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Mirko VölkersFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Haruhiro TokoFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Brett CollinsFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Lucy OrmacheaFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Kaitlen SamseFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Dieter A KubliFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Andrea De La TorreFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Andrew S KraftFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Asa B GustafssonFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Daniel P KellyFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.).
Mark A SussmanFrom the Department of Biology, San Diego State Heart Institute, San Diego State University, CA (S.D., M.H.K., B.J., J.E., M.V., H.T., B.C., L.O., K.S., A.D.L.T., M.A.S.); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla (D.A.K., A.B.G.); and Department of Medicine, Medical University of South Carolina Hollings Cancer Center, Charleston (A.S.K.), and Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, FL (D.P.K.). heartman4ever@icloud.com.
University of California, San Diego · USUniversity of Montana · US

Funding

Surgery, Physiology and ImmunohistopathologyP01HL085577 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI GUSTAFSSON, ASA B. · 2006 to 2017
$18.4M
REGULATION OF FATTY ACID OXIDATION DURING CARDIAC GROWTHR01HL058493 · NHLBI · WASHINGTON UNIVERSITY · PI KELLY, DANIEL PATRICK · 1998 to 2024
$10.6M
Regulation of Signal Transduction to Treat Heart FailureR01HL067245 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2001 to 2021
$6.0M
Stem Cell Signaling in the Pathologically Challenged MyocardiumR37HL091102 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2008 to 2017
$3.8M
A Genomic/Metabolomic Strategy to Characterize Cardiac Mitochondrial DysfunctionR01HL101189 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI KELLY, DANIEL PATRICK, MUOIO, DEBORAH M · 2010 to 2013
$2.9M
Beta-adrenergic signaling: double edged sword of myocardial repairR01HL117163 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2013 to 2017
$1.9M
Antagonism of myocardial aging and senescence with Pim-1 kinaseR01HL105759 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2011 to 2015
$1.8M
Enhanced Myocardial Repair with CardioClusters and CardioChimerasR01HL122525 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2014 to 2017
$1.5M
Cardioprotection by optimizing mTOR activityR01HL113647 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2013 to 2016
$1.5M
Molecular Engineering of Damaged Myocardium To Enhance Regeneration And RepairR01HL113656 · NHLBI · SAN DIEGO STATE UNIVERSITY · PI SUSSMAN, MARK ALAN · 2012 to 2013
$667k
NHLBI NIH HHS P01 HL085577NHLBI NIH HHS R01 HL058493NHLBI NIH HHS R01-HL058493NHLBI NIH HHS R01 HL067245NHLBI NIH HHS R01HL067245NHLBI NIH HHS R01 HL101189NHLBI NIH HHS R01-HL101189NHLBI NIH HHS R01 HL105759NHLBI NIH HHS R01HL105759NHLBI NIH HHS R01 HL113647NHLBI NIH HHS R01 HL113656NHLBI NIH HHS R01 HL117163NHLBI NIH HHS R01 HL122525NHLBI NIH HHS R37 HL091102NHLBI NIH HHS R37HL091102
6 · The paper itself

Abstract

rationaleThe senescent cardiac phenotype is accompanied by changes in mitochondrial function and biogenesis causing impairment in energy provision. The relationship between myocardial senescence and Pim kinases deserves attention because Pim-1 kinase is cardioprotective, in part, by preservation of mitochondrial integrity. Study of the pathological effects resulting from genetic deletion of all Pim kinase family members could provide important insight about cardiac mitochondrial biology and the aging phenotype.

objectiveTo demonstrate that myocardial senescence is promoted by loss of Pim leading to premature aging and aberrant mitochondrial function. METHODS AND

resultsCardiac myocyte senescence was evident at 3 months in Pim triple knockout mice, where all 3 isoforms of Pim kinase family members are genetically deleted. Cellular hypertrophic remodeling and fetal gene program activation were followed by heart failure at 6 months in Pim triple knockout mice. Metabolic dysfunction is an underlying cause of cardiac senescence and instigates a decline in cardiac function. Altered mitochondrial morphology is evident consequential to Pim deletion together with decreased ATP levels and increased phosphorylated AMP-activated protein kinase, exposing an energy deficiency in Pim triple knockout mice. Expression of the genes encoding master regulators of mitochondrial biogenesis, PPARγ (peroxisome proliferator-activated receptor gamma) coactivator-1 α and β, was diminished in Pim triple knockout hearts, as were downstream targets included in mitochondrial energy transduction, including fatty acid oxidation. Reversal of the dysregulated metabolic phenotype was observed by overexpressing c-Myc (Myc proto-oncogene protein), a downstream target of Pim kinases.

conclusionsPim kinases prevent premature cardiac aging and maintain a healthy pool of functional mitochondria leading to efficient cellular energetics.

Indexed as

Aging, PrematureAnimalsCardiomegalyCell Line, TransformedCell RespirationCellular SenescenceFibroblastsHumansMiceMice, KnockoutMitochondria, HeartMyocytes, CardiacPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaProto-Oncogene MasProto-Oncogene Proteins c-mycProto-Oncogene Proteins c-pim-1MAS1 protein, humanMyc protein, mousePeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPim1 protein, mousePim1 protein, ratPpargc1a protein, mouseProto-Oncogene MasProto-Oncogene Proteins c-mycProto-Oncogene Proteins c-pim-1RNA, Small InterferingTranscription Factorsaginghypertrophymetabolismproto-oncogene proteins pim

Identifiers

PMID24916111
PMCPMC4254755
OpenAlexW2156372445

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.