Evidence map›Paper›PMID 27034276›Full record

ArticleCirculation research2016

Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

Shavonn C Harper, Andrew Brack, Scott MacDonnell, Michael Franti, Bradley B Olwin, Beth A Bailey, Michael A Rudnicki, Steven R Houser

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

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
11.4field-weighted citation impact, top 1% 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

45 citing papers in PubMed, 72 citations in OpenAlex.

  1. Article
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  3. In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.American journal of physiology. Renal physiology · 2024
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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

8 authors at 4 institutions in 2 countries.

Shavonn C HarperFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Andrew BrackFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Scott MacDonnellFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Michael FrantiFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Bradley B OlwinFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Beth A BaileyFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Michael A RudnickiFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.).
Steven R HouserFrom the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.C.H., S.R.H.); Eli and Edythe Broad Center of Stem Cell Research and Regeneration Medicine, Department of Orthopaedic Surgery, University of California, San Francisco (A.B.); Department of Cardiovascular Research (S.M.), and Department of Research Beyond Borders (M.F.), Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT (S.M., M.F.); Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (B.B.O.); Department of Biology, Ursinus College, Collegeville, PA (B.A.B.); Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada (M.A.R.); and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada (M.A.R.). srhouser@temple.edu.
Ottawa Hospital Research InstituteOttawa Hospital · CABoehringer Ingelheim (United States) · USTemple University · US

Funding

Targeted Cancer Therapeutics and Heart Failure: Mechanisms and Post-injury RepairP01HL091799 · NHLBI · THOMAS JEFFERSON UNIVERSITY · PI HOUSER, STEVEN R · 2008 to 2018
$23.1M
PKC alpha as a translational target in Heart FailureP01HL108806 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RABINOWITZ, JOSEPH E · 2012 to 2016
$11.3M
The Role of Syndecans in Satellite Cell FunctionR01AR049446 · NIAMS · UNIVERSITY OF COLORADO AT BOULDER · PI Bradley B Olwin · 2005 to 2026
$7.2M
Calcium and Cardiac Regeneration after Myocardial InfarctionR01HL033921 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI HOUSER, STEVEN R · 1985 to 2017
$5.6M
Integrative Cardiovascular PathophysiologyT32HL091804 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ELROD, JOHN WILLIAM · 2008 to 2024
$4.5M
TRPC Channel Regulation of Cardiac Hypertrophy and ContractilityR01HL119229 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI HOUSER, STEVEN R · 2014 to 2017
$1.1M
NHLBI NIH HHS P01 HL091799NHLBI NIH HHS P01 HL108806NHLBI NIH HHS R01 HL033921NHLBI NIH HHS R01 HL119229NHLBI NIH HHS T32 HL091804NIAMS NIH HHS R01 AR049446
6 · The paper itself

Abstract

This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good.

Indexed as

AgingAnimalsBone Morphogenetic ProteinsCachexiaCells, CulturedDrug Evaluation, PreclinicalGrowth Differentiation FactorsHeartHumansHypertrophyMice, Inbred C57BLModels, AnimalMusclesMuscle, SkeletalMuscular DiseasesMyocardiumBone Morphogenetic ProteinsGDF11 protein, humanGdf11 protein, mouseGrowth Differentiation FactorsMyostatinRecombinant ProteinsSmad2 ProteinSmad3 Proteinaginggrowth factorsmyocardiummyokinespathological hypertrophy

Identifiers

PMID27034276
PMCPMC4829942
OpenAlexW2335672555

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.