Biology subjects

Faitg, J.

Publications and source records attributed to Faitg, J..

3 recordsLinked to original sources

bioRxiv2023

Urolithin A induces cardioprotection and enhanced mitochondrial quality during natural aging and heart failure

Cardiovascular diseases remain the primary cause of global mortality, necessitating effective strategies to alleviate their burden. Mitochondrial dysfunction is a driving force behind aging and chronic conditions, including heart disease. Here, we investigate the potential of Urolithin A (UA), a gut microbiome-derived postbiotic that enhances mitophagy, to ameliorate both age-related decline in cardiac function and cardiac failure. We highlight the significance of targeting mitochondria, by comparing gene expression changes in aging human hearts and cardiomyopathies. UA oral administration successfully counteracts mitochondrial and cardiac dysfunctions in preclinical models of aging and heart failure. UA improves both systolic and diastolic heart functions, distinguishing it from other mitochondrial interventions. In cardiomyocytes, UA recovers mitochondrial ultrastructural defects and decline in mitochondrial biomarkers occurring with aging and disease. These findings extend UAs benefits to heart health, making UA a promising nutritional intervention to evaluate in the clinic to promote healthy cardiovascular function as we age.

cell biology↗

bioRxiv2021

Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Autophagy is a stress-induced degradative process essential to cell survival. Recent studies have demonstrated that sepsis triggers sustained induction of autophagy in skeletal muscles, although the impact of this enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Atg7 is an autophagy gene that plays a major role in autophagosome formation. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis. Sepsis was induced using cecal ligation and perforation (CLP) with a sham operation serving as a control. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting and contractile dysfunction, hypoglycemia, higher ketone levels and a decreased in survival as compared to mice with intact Atg7. Several genes that encode 26S proteasome subunits were upregulated, suggesting that activation of the ubiquitin-proteasome system is responsible for the severe muscle atrophy that was seen in these mice. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced contractile and metabolic dysfunctions and negatively impacts survival. Induction of autophagy in skeletal muscles in response to sepsis thus represents a protective mechanism.

cell biology↗

bioRxiv2021

3D Neuronal Mitochondrial Morphology in Axons, Dendrites, and Somata of the Aging Mouse Hippocampus

The brains ability to process complex informations relies on the constant supply of energy through aerobic respiration by mitochondria. Neurons contain three anatomically distinct compartments - the soma, dendrites, and projecting axons - which have different energetic and biochemical requirements, as well as different mitochondrial morphologies in cultured systems. Here we apply a quantitative three-dimensional electron microscopy approach to map mitochondrial network morphology and complexity in the mouse brain. We examine three neuronal sub-compartments - the soma, dendrites, myelinated axons - in the dentate gyrus and CA1 of the mouse hippocampus, two subregions with distinct principal cell types and functions. We also establish compartment-specific differences in mitochondrial morphology across these cell types between young and old mice, highlighting differences in age-related morphological recalibrations. Overall, these data define the nature of the neuronal mitochondrial network in the mouse hippocampus, providing a foundation to examine the role of mitochondrial morpho-function in the aging brain.

neuroscience↗