ArticleEMBO reports2019
Loss of genomic integrity induced by lysosphingolipid imbalance drives ageing in the heart.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 38 citations in OpenAlex.
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- Study on the CHJ01 antitumor activity and mechanism via targeting sphingosine kinase 1 in A549 cells.Pharmaceutical science advances · 2025Article
- Age-dependent decline in sperm quality and function in a naturally short-lived vertebrate.BMC ecology and evolution · 2025Article
- Oxidative DNA Damage and Arterial Hypertension in Light of Current ESC Guidelines.International journal of molecular sciences · 2024Review
- Immune aging in annual killifish.Immunity & ageing : I & A · 2024Review
- Multi-omics analysis reveals attenuation of cellular stress by empagliflozin in high glucose-treated human cardiomyocytes.Journal of translational medicine · 2023Article
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- Artificial intelligence uncovers carcinogenic human metabolites.Nature chemical biology · 2022Article
- Fasting confers stress resistance to skeletal muscle stem cells through non-metabolic actions of β-hydroxybutyrate: implications in cardioprotection and aging.The journal of cardiovascular aging · 2022Article
- Genome-wide CRISPR/Cas9 screening in human iPS derived cardiomyocytes uncovers novel mediators of doxorubicin cardiotoxicity.Scientific reports · 2021Article
- Functional biodynamics of human-body system: A mathematical axiomatics with functional learning and aging in life cycle.Cognitive neurodynamics · 2020Article
- Article
- The aging transcriptome: read between the lines.Current opinion in neurobiology · 2020Review
- Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
Cardiac dysfunctions dramatically increase with age. Revealing a currently unknown contributor to cardiac ageing, we report the age-dependent, cardiac-specific accumulation of the lysosphingolipid sphinganine (dihydrosphingosine, DHS) as an evolutionarily conserved hallmark of the aged vertebrate heart. Mechanistically, the DHS-derivative sphinganine-1-phosphate (DHS1P) directly inhibits HDAC1, causing an aberrant elevation in histone acetylation and transcription levels, leading to DNA damage. Accordingly, the pharmacological interventions, preventing (i) the accumulation of DHS1P using SPHK2 inhibitors, (ii) the aberrant increase in histone acetylation using histone acetyltransferase (HAT) inhibitors, (iii) the DHS1P-dependent increase in transcription using an RNA polymerase II inhibitor, block DHS-induced DNA damage in human cardiomyocytes. Importantly, an increase in DHS levels in the hearts of healthy young adult mice leads to an impairment in cardiac functionality indicated by a significant reduction in left ventricular fractional shortening and ejection fraction, mimicking the functional deterioration of aged hearts. These molecular and functional defects can be partially prevented
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