Evidence map›Paper›PMID 33951438›Full record

ArticleCell reports2021

Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response.

Silvia Vaena, Paramita Chakraborty, Han Gyul Lee, Alhaji H Janneh, Mohamed Faisal Kassir, Gyda Beeson, Zachariah Hedley, Ahmet Yalcinkaya, M Hanief Sofi, Hong Li and 5 more

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

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.2field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 85 citations in OpenAlex.

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  4. CD8Science China. Life sciences · 2026
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  11. Mitochondria in focus: From structure and function to their role in human diseases. A review.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025
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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

15 authors at 3 institutions in 1 country.

Silvia VaenaDepartments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Paramita ChakrabortyDepartment of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Han Gyul LeeDepartments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Alhaji H JannehDepartments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Mohamed Faisal KassirDepartments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Gyda BeesonCollege of Pharmacy, Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Zachariah HedleyDepartment of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Ahmet YalcinkayaDepartments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
M Hanief SofiDepartment of Microbiology and Immunology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Hong LiHollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Department of Public Health, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Monica L HusbyDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Robert V StahelinDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Xue-Zhong YuDepartment of Microbiology and Immunology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Shikhar MehrotraDepartment of Surgery, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.
Besim OgretmenDepartments of Biochemistry and Molecular Biology, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA. Electronic address: ogretmen@musc.edu.
MUSC Hollings Cancer Center · USMedical University of South Carolina · USPurdue University West Lafayette · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Jian Ouyang · 2009 to 2026
$42.7M
Project 3: Targeting SK2/S1P Signaling for the Regulation of c-Myc and Tumor SuppressionP01CA203628 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BIELAWSKA, ALICJA · 2016 to 2021
$8.9M
Ceramide Signaling in the Regulation of Head & Neck Cancer Cell Death and TherapyR01DE016572 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2005 to 2025
$7.4M
RESEARCH PILOT PROJECTS PROGRAMP30GM103339 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI CROSSON, CRAIG E. · 2012 to 2016
$5.4M
Cellular, Biochemical and Molecular Sciences Training Program: Developing the skills and expertise needed for a changing biomedical landscapeT32GM132055 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Amy D Bradshaw, John P O'Bryan · 2019 to 2026
$3.9M
Research Supplement to Promote Diversity in Health-Related ResearchR01CA214461 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI Besim Ogretmen · 2018 to 2026
$3.3M
MUSC Post-Baccalaureate Research Education ProgramR25GM113278 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI DELEON-PENNELL, KRISTINE Y, PENROD-MARTIN, RACHEL · 2015 to 2024
$2.7M
MUSC FACIL EXPANSION &RENOV: SLE C06RR015455 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND, JOHN R · 2002 to 2002
$2.0M
Confocal/Multiphoton Microscope UpgradeS10OD018113 · OD · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI LEMASTERS, JOHN J · 2015 to 2015
$570k
Sphingolipid Metabolism and Signaling in the Regulation of Senescence and AgingR56AG069769 · NIA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI OGRETMEN, BESIM · 2020 to 2020
$370k
NCI NIH HHS P01 CA203628NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA214461NCRR NIH HHS C06 RR015455NIA NIH HHS R56 AG069769NIDCR NIH HHS R01 DE016572NIGMS NIH HHS P30 GM103339NIGMS NIH HHS R25 GM113278NIGMS NIH HHS T32 GM132055NIH HHS S10 OD018113
6 · The paper itself

Abstract

We lack a mechanistic understanding of aging-mediated changes in mitochondrial bioenergetics and lipid metabolism that affect T cell function. The bioactive sphingolipid ceramide, induced by aging stress, mediates mitophagy and cell death; however, the aging-related roles of ceramide metabolism in regulating T cell function remain unknown. Here, we show that activated T cells isolated from aging mice have elevated C14/C16 ceramide accumulation in mitochondria, generated by ceramide synthase 6, leading to mitophagy/mitochondrial dysfunction. Mechanistically, aging-dependent mitochondrial ceramide inhibits protein kinase A, leading to mitophagy in activated T cells. This aging/ceramide-dependent mitophagy attenuates the antitumor functions of T cells in vitro and in vivo. Also, inhibition of ceramide metabolism or PKA activation by genetic and pharmacologic means prevents mitophagy and restores the central memory phenotype in aging T cells. Thus, these studies help explain the mechanisms behind aging-related dysregulation of T cells' antitumor activity, which can be restored by inhibiting ceramide-dependent mitophagy.

Indexed as

AgingAnimalsCeramidesHumansMiceMitochondriaSignal TransductionT-LymphocytesCeramidesagingCerS6immunotherapylipid signalingmelanomamitophagyPKAsphingolipids and ceramideSS SphK2T cell

Identifiers

PMID33951438
PMCPMC8127241
OpenAlexW3157990394

What OpenQuestion holds

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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.