DEAD-box helicase 17(DDX17)protects cardiac function by promoting mitochondrial homeostasis in heart failure

DEAD-box helicase 17(DDX17)is a typical member of the DEAD-box family with transcriptional cofactor activity.Although DDX17 is abundantly expressed in the myocardium,its role in heart is not fully understood.We generated cardiomyocyte-specific Ddx17-knockout mice(Ddx17-cKO),cardiomyocyte-specific Ddx17 transgenic mice(Ddx17-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury.Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart failure.Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions.Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1(DRP1).When DDX17 expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1 expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart failure.We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure.These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Aging and aging-related diseases:from molecular mechanisms to interventions and treatments

Aging is a gradual and irreversible pathophysiological process.It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases,including neurodegenerative diseases,cardiovascular diseases,metabolic diseases,musculoskeletal diseases,and immune system diseases.Although the development of modern medicine has promoted human health and greatly extended life expectancy,with the aging of society,a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals.Current research on aging focuses on elucidating how various endogenous and exogenous stresses(such as genomic instability,telomere dysfunction,epigenetic alterations,loss of proteostasis,compromise of autophagy,mitochondrial dysfunction,cellular senescence,stem cell exhaustion,altered intercellular communication,deregulated nutrient sensing)participate in the regulation of aging.Furthermore,thorough research on the pathogenesis of aging to identify interventions that promote health and longevity(such as caloric restriction,microbiota transplantation,and nutritional intervention)and clinical treatment methods for aging-related diseases(depletion of senescent cells,stem cell therapy,antioxidative and anti-inflammatory treatments,and hormone replacement therapy)could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.