ArticleNature communications2019
Hydralazine targets cAMP-dependent protein kinase leading to sirtuin1/5 activation and lifespan extension in C. elegans.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.Frontiers in pharmacology · 2024Pooled it
- Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.Science advances · 2025Article
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Genome-wide RNAi screening in C. elegans reveals OXPHOS and pyrimidine synthesis pathways as PKA regulators.Communications biology · 2025Article
- ElixirSeeker: A Machine Learning Framework Utilizing Fusion Molecular Fingerprints for the Discovery of Lifespan-Extending Compounds.Aging cell · 2025Article
- Repurposing mitochondria-targeted therapeutics for kidney diseases.Kidney international · 2025Review
- cAMP-MFN2 signaling suppresses cochlear cell senescence and age-related hearing loss.Frontiers in immunology · 2025Article
- Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.bioRxiv : the preprint server for biology · 2024Article
- A randomized clinical trial evaluating Hydralazine's efficacy in early-stage Alzheimer's disease: The EHSAN Study.Scientific reports · 2024Article
- Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin.GeroScience · 2024Article
- TSG Extends the Longevity ofAntioxidants (Basel, Switzerland) · 2024Article
- Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues.Clinical epigenetics · 2024Review
- Review
- Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.Cell communication and signaling : CCS · 2024Review
- Spilanthes filicaulis (Schumach. & Thonn.) C.D. Adams leaves protects against streptozotocin-induced diabetic nephropathy.PloS one · 2024Article
- Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update.Journal of biomedical science · 2023Review
- Automated recognition and analysis of body bending behavior in C. elegans.BMC bioinformatics · 2023Article
- Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine.Stem cell research & therapy · 2023Article
- Quercetin Reprograms Immunometabolism of Macrophages via the SIRT1/PGC-1α Signaling Pathway to Ameliorate Lipopolysaccharide-Induced Oxidative Damage.International journal of molecular sciences · 2023Article
- Core-predominant gut fungus Kazachstania slooffiae promotes intestinal epithelial glycolysis via lysine desuccinylation in pigs.Microbiome · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Therapeutic activation of mitochondrial function has been suggested as an effective strategy to combat aging. Hydralazine is an FDA-approved drug used in the treatment of hypertension, heart failure and cancer. Hydralazine has been recently shown to promote lifespan in C. elegans, rotifer and yeast through a mechanism which has remained elusive. Here we report cAMP-dependent protein kinase (PKA) as the direct target of hydralazine. Using in vitro and in vivo models, we demonstrate a mechanism in which binding and stabilization of a catalytic subunit of PKA by hydralazine lead to improved mitochondrial function and metabolic homeostasis via the SIRT1/SIRT5 axis, which underlies hydralazine's prolongevity and stress resistance benefits. Hydralazine also protects mitochondrial metabolism and function resulting in restoration of health and lifespan in C. elegans under high glucose and other stress conditions. Our data also provide new insights into the mechanism(s) that explain various other known beneficial effects of hydralazine.
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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.