ArticleCell metabolism2017
DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 65 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.
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.
Who cites it
65 citing papers in PubMed, 126 citations in OpenAlex.
- Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Trial
- DNA-PKcs inhibition sensitizes glioblastoma to radiotherapy through reprogramming of tumor cell states and immune microenvironment cell types.Research square · 2026Article
- Improving our understanding of the biology of aging: findings from the Age-It Research Program.The journals of gerontology. Series B, Psychological sciences and social sciences · 2025Article
- DNA-PKcs-Driven YAP1 Phosphorylation and Nuclear Translocation: a Key Regulator of Ferroptosis in Hyperglycemia-Induced Cardiac Dysfunction in Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CD47-blocking antibody confers metabolic benefits against obesity.Cell reports. Medicine · 2025Article
- Utilization of natural products in diverse pathogeneses of diseases associated with single or double DNA strand damage repair.Chinese medicine · 2025Review
- Myristoylated Eepd1 Enhances Lipolysis and Thermogenesis through PKA Activation to Combat Obesity.Nature communications · 2025Article
- AMPK signaling in osteoarthritis: from mechanisms to targeted therapeutics.Frontiers in pharmacology · 2025Review
- DNA sensors in metabolic and cardiovascular diseases: Molecular mechanisms and therapeutic prospects.Immunological reviews · 2025Review
- Upstream targeting for the prevention of atrial fibrillation: Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)-rationale and study design.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2025Article
- Causal Relationship between Meat Intake and Biological Aging: Evidence from Mendelian Randomization Analysis.Nutrients · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- Article
- Regulation of the CB1R/AMPK/PGC-1α signaling pathway in mitochondria of mouse hearts and cardiomyocytes with chronic intermittent hypoxia.Sleep & breathing = Schlaf & Atmung · 2024Article
- Differential genetic expression within reward-specific ensembles in mice.bioRxiv : the preprint server for biology · 2024Article
- DNA-PKcs Phosphorylates Cofilin2 to Induce Endothelial Dysfunction and Microcirculatory Disorder in Endotoxemic Cardiomyopathy.Research (Washington, D.C.) · 2024Article
- The DNA-dependent protein kinase catalytic subunit promotes sepsis-induced cardiac dysfunction through disrupting INF-2-dependent mitochondrial dynamics.International journal of medical sciences · 2024Article
- Article
- TBC1D15 deficiency protects against doxorubicin cardiotoxicityActa pharmaceutica Sinica. B · 2023Article
- Impaired end joining induces cardiac atrophy in a Hutchinson-Gilford progeria mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
Hallmarks of aging that negatively impact health include weight gain and reduced physical fitness, which can increase insulin resistance and risk for many diseases, including type 2 diabetes. The underlying mechanism(s) for these phenomena is poorly understood. Here we report that aging increases DNA breaks and activates DNA-dependent protein kinase (DNA-PK) in skeletal muscle, which suppresses mitochondrial function, energy metabolism, and physical fitness. DNA-PK phosphorylates threonines 5 and 7 of HSP90α, decreasing its chaperone function for clients such as AMP-activated protein kinase (AMPK), which is critical for mitochondrial biogenesis and energy metabolism. Decreasing DNA-PK activity increases AMPK activity and prevents weight gain, decline of mitochondrial function, and decline of physical fitness in middle-aged mice and protects against type 2 diabetes. In conclusion, DNA-PK is one of the drivers of the metabolic and fitness decline during aging, and therefore DNA-PK inhibitors may have therapeutic potential in obesity and low exercise capacity.
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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.