ArticleAging cell2023
Cardiomyocyte Pdk4 response is associated with metabolic maladaptation in aging.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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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.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- PDK4 acts via hippo signaling to inhibit ferroptosis and reduce gemcitabine sensitivity in pancreatic cancer.Journal of molecular histology · 2026Article
- Regulatory mechanisms and interactions of mitophagy and ketone body metabolism in cardiac metabolism.Frontiers in cardiovascular medicine · 2026Review
- Article
- The dual role of ATF3 in myocardial repair through macrophage regulation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- S913 phosphorylation of Ulk1 protects the heart from aging through inhibition of cardiac senescence.Cardiovascular research · 2025Article
- Pyruvate Dehydrogenase Kinase 4 Underlies the Metabolic Disorder of Cardiomyocytes in Patients With Hypertrophic Cardiomyopathy From Hypertrophy to Heart Failure.Journal of the American Heart Association · 2025Article
- Acyl-CoA-binding protein as a driver of pathological aging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Single-Nucleus RNA Sequencing Reveals That Gabra6Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Global, regional, and national burden of ischemic heart disease attributable to lead exposure, 1990-2021: decomposition, frontier, and projection analysis.Frontiers in public health · 2025Article
- Dexmedetomidine Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting MDH2 Lactylation via Regulating Metabolic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Myeloid Cells in Myocardial Ischemic Injury: The Role of the Macrophage Migration Inhibitory Factor.Life (Basel, Switzerland) · 2024Review
- A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation.Metabolism: clinical and experimental · 2024Article
- Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer's disease by activated protein C.Aging · 2024Article
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- PDK4 rescues high-glucose-induced senescent fibroblasts and promotes diabetic wound healing through enhancing glycolysis and regulating YAP and JNK pathway.Cell death discovery · 2023Article
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- Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Ischemic heart disease (IHD) is the leading cause of death, with age range being the primary factor for development. The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. We aim to use single-cell RNA sequencing to discover transcriptional differences in various cell types between aged and young mice, which may contribute to aged-related vulnerability to ischemic insult. Utilizing 10× Genomics Single-Cell RNA sequencing, we were able to complete bioinformatic analysis to identity novel differential gene expression. During the analysis of our collected samples, we detected Pyruvate Dehydrogenase Kinase 4 (Pdk4) expression to be remarkably differentially expressed. Particularly in cardiomyocyte cell populations, Pdk4 was found to be significantly upregulated in the young mouse population compared to the aged mice under ischemic/reperfusion conditions. Pdk4 is responsible for inhibiting the enzyme pyruvate dehydrogenase, resulting in the regulation of glucose metabolism. Due to decreased Pdk4 expression in aged cardiomyocytes, there may be an increased reliance on glucose oxidization for energy. Through biochemical metabolomics analysis, it was observed that there is a greater abundance of pyruvate in young hearts in contrast to their aged counterparts, indicating less glycolytic activity. We believe that Pdk4 response provides valuable insight towards mechanisms that allow for the young heart to handle ischemic insult stress more effectively than the aged heart.
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Registered trials
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.