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FGF21-Mediated Upregulation of SIRT1 Delays Intervertebral Disc Degeneration by Promoting PINK1/Parkin Dependent Mitophagy Through Deacetylation of FOXO3

13 hours 48 minutes ago
Intervertebral Disc Degeneration (IDD) is a common degenerative spinal disease and a leading cause of low back pain and disability. The senescence of nucleus pulposus cells (NPCs) is a central mechanism driving the pathological progression of IDD, though its regulatory mechanisms remain unclear. Bioinformatic analysis identified FGF21 as a key gene regulating NPCs senescence. In both human and rat degenerated intervertebral discs, FGF21 expression was significantly downregulated and closely...
Zuo-Long Wu

Age-Like Methylation Changes of HSCs in GADD45B Knockout Mice Define Methylation Sites Associated With Loss of Function

13 hours 48 minutes ago
Hematopoietic stem cells (HSCs) self-renew and differentiate into all blood cells maintaining the hematopoietic system. Age-related HSC dysfunction impacts all of hematopoiesis, with DNA methylation alterations in aged HSCs contributing to altered function. Growth Arrest and DNA Damage-inducible proteins (Gadd45a, Gadd45b, and Gadd45g) are expressed in HSC activation, and Gadd45b has been reported to induce DNA demethylation. Thus, we explored the relationship between Gadd45b, DNA methylation...
Wakako Kuribayashi

Parkinson's disease-associated PLA2G6 protects IP3R1 protein to control ER-mitochondria tethering and Ca(2+) transfer

13 hours 48 minutes ago
Mutations in the phospholipase A2 group VI (PLA2G6) gene have been linked to autosomal recessive Parkinson's disease (PD), yet the molecular mechanisms remain poorly understood. This study provides the in vitro and in vivo evidence, specifically in dopaminergic neurons derived from patients with PD, that PLA2G6 loss-of-function disrupts the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), a critical regulator of Ca^(2+) transfer and energy homeostasis. This study demonstrates...
Zhi-Hao Lin

Membrane interfacial potential governs surface condensation and fibrillation of α-Synuclein in neurons

13 hours 48 minutes ago
Biomolecular condensates formed via liquid-liquid phase separation (LLPS) are essential for cellular organization. α-Synuclein, an amyloidogenic protein linked to Parkinson's Disease (PD), undergoes phase separation at high concentrations, but the influence of lipid membranes on this process remains unclear. Here, combining in vitro reconstitution, cell biology, and simulations, we show that membranous interfaces promote α-Synuclein condensation at physiologically relevant sub-critical...
Jafarulla Shaikh

StrucGAP: a modular, streamlined and traceable data mining platform for structural and site-specific glycoproteomics

13 hours 48 minutes ago
The rapidly developing search engines for glycopeptide identification and accumulated high-resolution glycoproteomic data underscore the need for robust downstream data mining platforms towards subsequently functional and mechanistic studies. Here, we introduce StrucGAP, a Structural Glycoproteomics Analysis Platform for scalable downstream data mining of site-specific N-glycoproteomics. It integrates modules for data quality control, overall glycan structural characterization, altered glycan...
Muyao Yang

IVNS1ABP mutation drives cellular senescence in newly identified progeroid neuropathy

13 hours 48 minutes ago
We identified a new progeroid syndrome with severe neuropathy and intellectual deficits but its underlying cellular and molecular mechanism is unknown. Exome sequencing revealed a homozygous mutation in the IVNS1ABP gene, which encodes IVNS1ABP, an influenza virus non-structural protein-1 binding protein. To investigate disease mechanisms, we generated isogenic induced pluripotent stem cells (iPSCs) from patient fibroblasts and differentiated them into neural progenitor cells (NPCs). Mutant...
Fang Yuan

The brain-gut-muscle axis: a mechanism for exercise-mediated protection in brain aging

13 hours 48 minutes ago
The global challenge of population aging underscores the critical need to delay brain aging and cognitive decline, a pressing public health issue. The brain-gut-muscle axis is a complex regulatory network connecting skeletal muscle, gut microbiota, and the brain. It has received considerable research attention for its crucial role in maintaining brain health and counteracting aging. As a safe and effective non-pharmacological intervention, exercise modulates gut microbiota composition and...
Wenyu Sun

TAS2R38 taster variants-linked MGAM expression in Alzheimer's disease: a novel target for precision drug repurposing

13 hours 48 minutes ago
INTRODUCTION: TAS2R38 is a taste receptor gene located on human chromosome 7 that influences sensitivity to bitter tastes and has been implicated in innate immunity, glucose level, and human longevity. However, its potential association with Alzheimer's Disease (AD) has not been explored. Identifying such a genetic connection could support developing new drugs or repurposing existing ones for AD treatment.
Claire W Su

Diet, gut microbiome, and cognition in neurodegeneration: a review and methodological framework

13 hours 48 minutes ago
The gut microbiome influences brain function through the gut-brain axis via synthesis of neurotransmitters, production of metabolites affecting epithelial barrier integrity and immune modulation and signaling through the vagus nerve. In humans, microbiome diversity reflects healthy aging and predicts survival, while dysbiosis is increasingly implicated in neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS. Fecal transplant studies in...
Jacob Raber

Age-related changes in static and dynamic postural balance performance

13 hours 48 minutes ago
CONCLUSION: Age-related changes in balance control are task dependent. Older adults preserved static balance performance but demonstrated impaired reactive balance responses in dynamic tasks. Furthermore, static and dynamic balance rely on distinct control mechanisms, highlighting the need for separate assessments.
A Rizzato