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Hydralazine Improves Mitochondrial Function via SIRT1/SIRT5 Activation and Protects against Glucose Toxicity
Author(s) -
Mirzaei Hamid Harrison,
Dehgan Esmaeil
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb27
Subject(s) - hydralazine , pharmacology , mitochondrion , function (biology) , drug , longevity , medicine , biology , bioinformatics , chemistry , microbiology and biotechnology , gerontology , blood pressure
Mitochondrial dysfunction is one of the hallmarks of aging. Improving mitochondrial activity has been a prime target for improving organismal fitness and longevity and in many cases a potential treatment for age‐related diseases. In this study, we demonstrate that hydralazine, an FDA approved antihypertensive drug, improves mitochondrial function in a SIRT1/SIRT5‐dependent manner. We show that hydralazine treatment alters central carbon metabolism, increases TCA cycle metabolites, and improves respiration in C. elegans . Our data suggest that hydralazine‐induced mitochondrial activation is essential for the drug's prolongevity effect in C. elegans . We demonstrate that under glucose stress, hydralazine treatment restores locomotor performance, mitochondrial health, and lifespan in C. elegans . These new insights into hydralazine's ability to alter the mitochondrial activity and metabolic homeostasis deepen our understanding of hydralazine's mechanism of action and its potential health benefits and side effects. Support or Funding Information This work was supported by the National Institutes of Health (grant R03AG045504 to H.M.), Robert A. Welch Foundation (grant I‐1850 to H.M.) and the Cancer Prevention and Research Institute of Texas (grant R1121 to H.M.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .