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

1 month 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

1 month 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

1 month 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

1 month 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

1 month 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

Tissue morphology predicts telomere shortening in human tissues

1 month ago
We present TLPath, a deep learning framework that predicts bulk-tissue telomere length from tissue morphology extracted from routine histopathology images. The central thesis of TLPath is that telomere length can be determined from tissue morphology. Trained on >5,000 whole-slide images across 919 individuals and 18 organs, TLPath discovers that extracted morphological features naturally separate young, middle-aged, and elderly individuals, demonstrating that aging causes architectural changes...
Anamika Yadav

The Adiponectin-PP2A Pathway Confers Cognitive Benefits of Physical Exercise Against Chronic Stress-Induced Tau Hyperphosphorylation in the Hippocampus

1 month ago
Protein phosphatase 2A (PP2A) regulates Tau hyperphosphorylation in Alzheimer's disease (AD). This study hypothesized that exercise increases adiponectin levels, activating PP2A to reduce Tau hyperphosphorylation and enhance hippocampal plasticity. The study utilized adiponectin knockout (Adipo^(-/-)) and hippocampal-specific PP2A knockdown (PP2A-KD) in mice with 3-week voluntary running and/or chronic stress to assess changes in Tau phosphorylation, adult neurogenesis, and cognitive...
Hui-Hui Guo

Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex

1 month ago
Single-cell spatial transcriptomes have demonstrated molecular and cellular diversity in the brain, but gene regulatory mechanisms underlying transcriptomic profiles and disease pathogenesis remain largely unknown in primates. Here we performed single-nucleus Assay for Transposase-Accessible Chromatin followed by sequencing (snATAC-seq) for ~1.6 million cells from 142 cortical regions of two male cynomolgus monkeys (Macaca fascicularis), and identified distinct chromatin accessibility profiles...
Juan Meng

Maintaining and regaining episodic memory in Alzheimer disease: a circuit-based perspective

1 month ago
Losing track of personal experiences is a defining feature of Alzheimer disease (AD), arising from the spread of AD pathology through the brain circuits that support episodic memory. In this Review, we explore strategies to improve the function of episodic memory circuits in AD by leveraging the optimized use of neural resources. We introduce the circuit utilization framework, which builds on evidence that synaptic dysfunction, maladaptive responses and deficient adaptive plasticity contribute...
Emrah Düzel

Reversible crosslinking strategy for dynamic strain regulation in inverted perovskite solar cells

1 month ago
Perovskite solar cells tend to degrade much faster under day-night cycling conditions. One key reason lies in the periodic strain in perovskite film under cycling mode due to its soft crystal lattice nature. Here, we propose a dynamic reversible crosslinking strategy by introducing disulfide-mediated cross-linkable additive of 2-methacryloyloxyethyl-thioctate. Combining with carbon-carbon double bond, 2-methacryloyloxyethyl-thioctate crosslinks at grain boundaries at high temperature through...
Wen Li

Hydroxychloroquine alleviates cyclophosphamide-induced premature ovarian failure by attenuating granulosa cell senescence and modulating the mtDNA-cGAS pathway

1 month ago
Cyclophosphamide (CTX) is a first-line chemotherapeutic agent for various cancers but is associated with a significant risk of ovarian dysfunction, which may even progress to premature ovarian failure (POF). Granulosa cell senescence is a key phenotypic manifestation of this process. Hydroxychloroquine (HCQ) exerts anti-senescence effects in age-related diseases; however, its efficacy in preventing CTX-induced ovarian damage remains elusive. We aimed to verify the protective effect of HCQ using...
Dehui Su

Cycloneolitsol prolongs the lifespan of Caenorhabditis elegans by SEK-1/PMK-1/SKN-1 pathway and exerts anti-inflammatory effects by NF-kappaB pathway

1 month ago
Aging is a major risk factor for the onset and progression of many neurodegenerative diseases. Inflammation is the body's natural defense mechanism against harmful stimuli. A growing body of research has highlighted the intricate relationship between aging and inflammation, with chronic low-grade inflammation, often referred to as "inflammaging," being a hallmark of the aging process. Cycloneolitsol (CL) is a C-32 cycloartane-type triterpene from Taxodium ascendens which has been reported to...
Xiaoli Zhang