Simon Sedej
A5082405402- Cardiac electrophysiology and arrhythmias
- Autophagy in Disease and Therapy
- Adipose Tissue and Metabolism
- Ion channel regulation and function
- Cardiovascular Function and Risk Factors
- Cardiomyopathy and Myosin Studies
- Cannabis and Cannabinoid Research
- Cardiac Fibrosis and Remodeling
- Polyamine Metabolism and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Sirtuins and Resveratrol in Medicine
- Pancreatic function and diabetes
- Dietary Effects on Health
- Cellular transport and secretion
- Signaling Pathways in Disease
- Atrial Fibrillation Management and Outcomes
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Cardiovascular Effects of Exercise
- RNA modifications and cancer
- Diet and metabolism studies
- Adenosine and Purinergic Signaling
- Erythrocyte Function and Pathophysiology
- Cardiac Ischemia and Reperfusion
BioTechMed-Graz
2017-2025
Medical University of Graz
2016-2025
University of Maribor
2020-2025
University of Graz
2017-2024
Washington University in St. Louis
2023
Graz University Hospital
2021
Medical University of Vienna
2019
Wilhelminen Hospital
2019
University of California, Davis
2014
Cardiff Metropolitan University
2014
Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by triglyceride lipase (ATGL) is considered a key step NST. Accordingly, the severe cold intolerance global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Here we show that this conclusion incorrect. We demonstrate although BAT-specific loss impairs lipolysis alters morphology, it does not compromise...
Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status cells affects both and autophagy through as-yet-elusive metabolic circuitries. Here, we show nucleocytosolic acetyl-coenzyme A (AcCoA) production a repressor during yeast. Blocking the mitochondrial route to AcCoA deletion CoA-transferase ACH1 caused cytosolic accumulation precursor acetate. This led hyperactivation AcCoA-synthetase Acs2p, triggering histone...
Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective lifespan-extending effects dietary spermidine, natural autophagy-promoting polyamine. Here, we show that spermidine passes blood-brain barrier in mice increases hippocampal eIF5A hypusination mitochondrial function. Spermidine feeding aged affects behavior homecage environment tasks, improves...
The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
Background: The insulin-like growth factor 1 (IGF1) pathway is a key regulator of cellular metabolism and aging. Although its inhibition promotes longevity across species, the effect attenuated IGF1 signaling on cardiac aging remains controversial. Methods: We performed lifelong study to assess health lifespan in 2 cardiomyocyte-specific transgenic mouse models with enhanced versus reduced receptor (IGF1R) signaling. Male mice human IGF1R overexpression or dominant negative phosphoinositide...
Abstract Caloric restriction and intermittent fasting prolong the lifespan healthspan of model organisms improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection reduced incidence cardiovascular neurodegenerative diseases across species borders. Here, we asked whether cellular physiological consequences caloric depend on metabolism. We report that levels increased upon distinct regimens or in yeast, flies, mice volunteers....
Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report identification of flavonoid 4,4'-dimethoxychalcone (DMC) as a natural compound anti-ageing properties. External DMC administration extends lifespan yeast, worms flies, decelerates senescence human cell cultures,...
Nicotinamide adenine dinucleotide (NAD + ) is a central metabolite involved in energy and redox homeostasis as well DNA repair protein deacetylation reactions. Pharmacological or genetic inhibition of NAD -degrading enzymes, external supplementation precursors, transgenic overexpression -generating enzymes have wide positive effects on metabolic health age-associated diseases. pools tend to decline with normal aging, obesity, hypertension, which are all major risk factors for cardiovascular...
Atrial fibrillation (AF) and heart failure often coexist, but their interaction is poorly understood. Clinical data indicate that the arrhythmic component of AF may contribute to left ventricular (LV) dysfunction. This study investigates effects molecular mechanisms on human LV. Ventricular myocardium from patients with aortic stenosis preserved LV function sinus rhythm or rate-controlled was studied. showed no differences in fibrosis. In functional studies, systolic Ca2+ transient amplitude...
AimsMutations in the cardiac ryanodine receptor Ca2+ release channel, RyR2, underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited life-threatening arrhythmia. CPVT is triggered by spontaneous RyR2-mediated sarcoplasmic reticulum (SR) response to SR overload during β-adrenergic stimulation. However, whether elevated content—in absence of protein kinase A activation—affects RyR2 function and arrhythmogenesis remains elusive.
A hallmark of heart failure is impaired cytoplasmic Ca(2+) handling cardiomyocytes. It remains unknown whether specific alterations in nuclear via altered excitation-transcription coupling contribute to the development and progression failure.Using tissue isolated cardiomyocytes from nonfailing failing human hearts, as well mouse rabbit models hypertrophy failure, we provide compelling evidence for structural functional changes envelope remodeling progresses. Increased size less frequent...
Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity natural autophagy inducer spermidine in animal models aging hypertension, which both represent major risk factors for development Dietary elicits cardioprotective effects aged mice through enhancing mitophagy. In salt-sensitive rats, supplementation also delays hypertensive disease,...
Rationale: CaMKII (Ca 2+ -Calmodulin dependent protein kinase) δC activation is implicated in pathological progression of heart failure (HF) and CaMKIIδC transgenic mice rapidly develop HF arrhythmias. However, little known about early spatio-temporal Ca handling hypertrophy HF. Objective: To measure time- location-dependent signaling adult ventricular cardiomyocytes, during transaortic constriction (TAC) mice. Methods Results: We used human tissue from nonfailing hearts, 4 mouse lines:...
Autophagy protects against the development of cardiac hypertrophy and failure. While aberrant Ca2+ handling promotes myocardial remodelling contributes to contractile dysfunction, role autophagy in maintaining homeostasis remains elusive. Here, we examined whether Atg5 deficiency-mediated early changes subcellular ventricular cardiomyocytes, those alterations associate with compromised reserve capacity, which commonly precedes onset heart failure.RT-qPCR immunoblotting demonstrated reduced...
Synchronized release of Ca²⁺ into the cytosol during each cardiac cycle determines cardiomyocyte contraction.
Ca²⁺ leak from the sarcoplasmic reticulum (SR) via ryanodine receptors (RyR2s) contributes to cardiomyocyte dysfunction. RyR2 has been related phosphorylation. In these conditions, JTV519 (K201), a 1,4-benzothiazepine derivative and multi-channel blocker, stabilizes RyR2s decrease SR leak. We investigated whether without increasing phosphorylation in mice non-failing human myocardium explored underlying mechanisms.SR was induced by ouabain murine cardiomyocytes. [Ca²⁺]-transients, load...