Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Objective: Cardiac function declines with age, impairing exercise tolerance and negatively impacting healthy aging. However, mechanisms driving age-related declines in cardiac function are not fully understood.
Methods: We examined mechanisms underlying age-related cardiac dysfunction using 3- and 24-month-old wild-type mice fed ad libitum or 24-month-old wild-type mice subjected to 70% calorie restriction (CR) starting at 2-month-old. In addition, cardiac aging phenotypes and mitochondrial biogenesis were also analyzed in 25-month-old cardiac-specific Hint1 knockout mice, 24-month-old CAG-Caren Tg mice, and 24-month-old wild-type mice injected with AAV6-Caren.
Results: We observed inactivation of mitochondrial biogenesis in hearts of aged mice. We also showed that activity of the BAF chromatin remodeling complex is repressed by HINT1, whose expression in heart increases with age, leading to decreased transcription of Tfam, which promotes mitochondrial biogenesis. Interestingly, CR not only suppressed age-related declines in cardiac function and mitochondrial biogenesis but blocked concomitant increases in cardiac HINT1 protein levels and maintained Tfam transcription. Furthermore, expression of the lncRNA Caren, which inhibits Hint1 mRNA translation, decreased with age in heart, and CR suppressed this effect. Finally, decreased HINT1 expression due to Caren overexpression antagonized age-related declines in mitochondrial biogenesis, ameliorating age-related cardiac dysfunction, exercise intolerance, and exercise-induced cardiac damage and subsequent death of mice.
Conclusion: Our findings suggest that mitochondrial biogenesis in cardiomyocytes decreases with age and could underlie cardiac dysfunction, and that the Caren-HINT1-mitochondrial biogenesis axis may constitute a mechanism linking CR to resistance to cardiac aging. We also show that ameliorating declines in mitochondrial biogenesis in cardiomyocytes could counteract age-related declines in cardiac function, and that this strategy may improve exercise tolerance and extend so-called "healthy life span".
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850129 | PMC |
| http://dx.doi.org/10.1016/j.molmet.2025.102107 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of Brown Rice, Meal Replacements, and Anti-Obesity Drugs on Mitochondria in Obese Rats.
Diabetes Metab Syndr Obes
September 2025
School of Medical, Indigenous and Health, University of Wollongong, Wollongong, New South Wales, Australia.
Introduction: Obesity remains a critical global health challenge, intricately linked to poor dietary quality, gut microbiota dysbiosis, and mitochondrial dysfunction.
Purpose: This study aimed to investigate the comparative effects of brown rice, meal replacements, and thiazolidinediones on mitochondrial abundance and gut microbiota composition in a rat model of diet-induced obesity.
Methods And Materials: A total of twenty male Sprague Dawley rats were randomly assigned to five groups: control, high-fat high-fructose diet, and three intervention groups receiving the same obesogenic diet supplemented with brown rice, meal replacement, or thiazolidinediones for twelve weeks.
Aging is associated with cognitive decline, impaired spatial learning, and diminished brain function, significantly impacting quality of life (QoL). Emerging evidence suggests that lifestyle interventions, like omega-3 fatty acids (FAs) intake and regular exercise, can mitigate these age-related deficits by targeting key molecular pathways implicated in oxidative damage, inflammation, and reduced fibrinolytic activity. By doing so, omega-3 FAs, principally eicosapentaenoic acid and docosahexaenoic acid, influence signaling pathways that enhance synaptic plasticity, prevent apoptosis, and promote neurogenesis.
View Article and Find Full Text PDFBlack raspberry is known to contain a diverse number of phytochemicals, especially polyphenols which have shown health benefits. These compounds might play a role in alleviating β-amyloid (Aβ)-induced neurotoxicity. In this study, we investigated the effect of black raspberry in reducing Aβ toxicity and improving mitochondrial function in the HT-22 cell model.
View Article and Find Full Text PDFEpigenetic modulation by life-style: advances in diet, exercise, and mindfulness for disease prevention and health optimization.
Front Nutr
August 2025
Laboratorio para Investigaciones Biomédicas, Facultad de Ciencias de la vida, Escuela Superior Politécnica del Litoral (ESPOL), Campus Gustavo Galindo, Guayaquil, Ecuador.
Socio-economic and environmental factors significantly influence health by driving epigenetic changes that alter genetic expression and impact disease prevention. Lifestyle elements such as diet, exercise, mindfulness, and environmental exposure play crucial roles in modulating these mechanisms. A systematic review of studies from the past 13 years, conducted under PRISMA guidelines, examined interventions, epigenetic outcomes, and health impacts.
View Article and Find Full Text PDFBacteria-Mitochondria Cross-talk: How Microbes Regulate Mitochondrial Dynamics and Bioenergetics of Host Cells.
Infect Disord Drug Targets
August 2025
Department of Biochemistry and Microbiology, North South University, Bashundhara, Dhaka, Bangladesh.
Mitochondria are the cellular powerhouses and are considered to be central to energy metabolism, dynamics, and homeostasis. There is growing evidence that the gut microbiome regulates mitochondrial biogenesis, dynamics (fission, fusion, mitoph-agy), and bioenergetics, and that it does so by connecting bacterial metabolites and signaling molecules. This review discusses the molecular mechanisms that underlie the interplay between bacteria and mitochondria, with a particular focus on the modulation of mitochondrial activities by microbial products, including bile acids, immunological mediators, and short-chain fatty acids (SCFAs).
View Article and Find Full Text PDF