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ATP13A2 restrains macrophage NLRP3 inflammasome activation to repress neurodegeneration via modulating mitochondrial homeostasis

2 weeks 4 days ago
Neuro-immune crosstalk is increasingly recognized in Parkinson's disease (PD), and ATP13A2 is well known for its neuroprotective role. However, it remains unclear whether ATP13A2 mutations carried by PD patients contribute to immune dysfunction that exacerbates disease progression. Here, we systematically demonstrate that many ATP13A2 mutations result in a loss-of-expression phenotype. ATP13A2 is highly expressed in macrophages. Myeloid ATP13A2 deficiency causes uncontrolled NLRP3 inflammasome...
Ziqi Zou

Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice

2 weeks 4 days ago
The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan benefits of these proposed interventions in other models or under different conditions, none of the tested compounds significantly increased lifespan in male or female mice....
Ron Korstanje

Comprehensive profiling of skin microbiome diversity and major determinants in a multi-regional Chinese population

2 weeks 4 days ago
The human skin microbiome is essential for health and is shaped by both host and environmental factors. To establish a nationwide baseline, we profile the skin microbiome of 1,029 Chinese individuals across three body sites (hand, axilla, and foot), four geographic regions, and four ethnic groups using 16S rRNA gene sequencing. Within each skin site, we identify two cutotypes, one of which is consistently dominated by Staphylococcus. Microbial diversity and community composition vary across body...
Wan-Xue Zhang

Senolytic treatment induces oligodendrocyte dysfunction and demyelination in the corpus callosum

2 weeks 4 days ago
Aging is a primary risk factor for disease progression in multiple sclerosis (MS). Because of this, treatments that can reduce the consequences of molecular aging, like senescence, have been proposed as a strategy to address disease progression. However, the effects of senolytics, a class of drugs which selectively ablate senescent cells, on the central nervous system are largely unknown. Here, we examined the effects of senolytic treatment on myelination and oligodendrocyte function in vivo...
Evan R Lombardo

Plasma proteomic signature of frailty in 50,506 adults

2 weeks 4 days ago
Proteomics enables the systematic elucidation of biological mechanisms underlying frailty. Through a large proteome-wide association study of 2,911 plasma proteins from 50,506 UK Biobank participants, we identified 1,339 proteins significantly associated with frailty, highlighting collagen-containing extracellular matrix and vesicle lumen pathways. Replication in the TwinGene study confirmed partial but consistent associations. Mendelian randomization analyses identified five potentially causal...
Xueqing Jia