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Fusidic acid (FA) is one of few remaining antibiotics active against Methicillin-resistant Staphylococcus aureus. FusB confers resistance to FA by rescuing the translocation factor Elongation Factor-G (EF-G) from FA-stalled ribosome complexes. FusB induces allosteric effects on dynamics in EF-G, causing significant changes in the conformational flexibility of domain III that result in an increase in a minor, more disordered state, overcoming the steric block induced by FA. We show that...

During brain aging, terminally differentiated neuroglia exhibit metabolic dysfunction and increased oxidative damage, compromising their function. These cellular and molecular alterations impair their ability to maintain myelin sheath integrity, contributing to age-related white matter degradation. Calorie restriction (CR) is a well-established intervention that can slow biological aging and may reduce age-related metabolic alterations, thereby preserving the molecular function of aging glia....

Cellular senescence and necroptosis are two cell fates, which trigger an inflammatory response and increase with age, that have been proposed to play a role in inflammaging. In this study, we performed the first study to directly test the possible interaction between necroptosis and cellular senescence. Using a novel Mlkl-KI mouse model, we were able to specifically induce (~ 4-fold) the overexpression of MLKL, the necroptotic executioner, in hepatocytes (hMlkl-KI mice). The overexpression of...

Bone marrow exhibits functional decline, yet cellular heterogeneity and molecular mechanisms remain unclear due to limitations of traditional research methods. This study aims to characterize age-related changes and identify key drivers in bone marrow. Integrated multi-omics analysis was performed using scRNA-seq, proteomics, pseudo-bulk transcriptomics, weighted gene co-expression network analysis (WGCNA)-based transcription factor (TF) network modeling, and CellChat analysis. Samples included...

The human brain is one of the most metabolically active tissues in the body, due in large part to the activity of trillions of synaptic connections. Under normal conditions, macroautophagy/autophagy at the synapse plays a crucial role in synaptic pruning and plasticity, which occurs physiologically in the absence of disease- or aging-related stressors. Disruption of autophagy has profound effects on neuron development, structure, function, and survival. Neurons are dependent upon maintaining...

The amyloid precursor protein (APP) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). While the production of Amyloid beta (Aβ) has traditionally been considered the primary cause of AD, the role of the APP intracellular domain (AICD) remains largely elusive. In this study, we established a novel model in the adult fly wing by expressing human APP, recapitulating AD-associated axon degeneration. Using this model, we discovered that ectopic APP expression in Drosophila wing...

The human brain is one of the most metabolically active tissues in the body, due in large part to the activity of trillions of synaptic connections. Under normal conditions, macroautophagy/autophagy at the synapse plays a crucial role in synaptic pruning and plasticity, which occurs physiologically in the absence of disease- or aging-related stressors. Disruption of autophagy has profound effects on neuron development, structure, function, and survival. Neurons are dependent upon maintaining...

Preovulatory follicle aging is the period between formation and ovulation of a mature follicle. Previous studies had shown that mammalian preovulatory follicle aging is associated with chromosomal abnormalities and developmental defects such as decreased implantation, increased malformation and mortality and lower embryonic weight. Our understanding of the molecular events governing this process has been hampered by the difficulty in accessing them in vivo under natural conditions. We...

Policy drops “paylines” based on peer-review scores and requires geography and other factors to guide approvals