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PINK1 serves as the central regulator of PINK1-PRKN-mediated mitophagy, and its precise regulation is critical for efficient mitochondrial clearance. Although the cleavage of PINK1 and its subsequent degradation via the N-end rule pathway under basal conditions are well understood, how full-length PINK1 stability is regulated following mitochondrial damage has remained elusive. In our recent study, we identified the STUB1-VCP/p97 axis as a mechanism that fine-tunes full-length PINK1 levels...

Unusual radio signals could be long-sought smoking gun of galactic mergers

Glial crosstalk surrounding amyloid-β (Aβ) plaques establishes a self-propagating inflammatory niche fueling Alzheimer's disease (AD), yet the molecular triggers remain incompletely defined. We found that the calcium-dependent enzyme peptidyl-arginine deiminase 2 (PAD2) was selectively upregulated in plaque-associated astrocytes in human AD cortex and multiple APP AD transgenic mouse models. Astrocyte-specific deletion of Padi2 in 5×FAD mice rescued learning and memory, lowered Aβ load,...

One essential post-transcriptional regulatory mechanism that increases protein diversity in eukaryotes is alternative splicing. This process is crucial for maintaining nervous system function and is highly active in neurons. Dysregulation of alternative splicing is a common pathogenic factor in many neurodegenerative diseases. For example, splicing variants of tau protein and amyloid precursor protein are implicated in Alzheimer's disease; aberrant splicing of α-synuclein (SNCA) and upregulation...

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Despite the well-known role as degradative organelles, lysosomes have been identified as a central signaling hub in maintaining cellular homeostasis. Lysosomal dysfunction is a well-established driver of cellular senescence and age-related pathologies. However, the precise molecular mechanisms through which lysosomes actively regulate aging remain unclear. Excitingly, latest studies show that lysosomes are not merely passive in aging but may actively govern longevity. In this review we summarize...

Promoting brain health is vital for well-being and reducing healthcare burdens. Brain health as measured with the Brain Age Gap (BAG) - the difference between chronological and predicted brain age- relates to many factors. However, a holistic view, integrating the range of factors an individual brain is exposed to, is missing for understanding how the exposome shapes brain health. After computing BAG as an indicator of grey matter (GM) health, we predicted it using machine learning based on 261...

Lab-scale wastewater treatment studies, including urine recovery, often rely on oversimplified synthetic wastewater, thereby compromising the reliability of results and data. Here, we systematically evaluate how using full-component versus simplified synthetic urine formulations affects the performance and engineering-economic assessment of bipolar membrane electrodialysis. Our findings reveal that simplification fundamentally alters fouling mechanisms. While urea alone causes significant damage...

Pleural Mesothelioma (PM) is an aggressive neoplasm of the lung pleura with poor survival rates, highlighting the urgent need for novel therapeutic options. The CDK4/6 inhibitors abemaciclib and palbociclib have demonstrated promising results in patient-derived xenograft models of PM. In this study, we observed that palbociclib reduced proliferation, leading to increased cell size, enhanced SA-β-galactosidase activity, and elevated secretion of IL-6 and IL-8 (SASP), all of which are hallmarks of...

Abnormal cell fate transition determines cell instability, which can contribute to disease development. In chronic kidney disease, many renal tubular cells exhibit senescent phenotypes. The fundamental mechanisms of this fate transition remain undetermined. Here we discover that WNT10B, a ligand of the Wnt family, accelerates CKD progression through tubular senescence and proinflammatory microenvironments. Mechanistically, WNT10B mediates metabolic reprogramming from fatty acid oxidation to...

Immune defenses decline with age, increasing susceptibility to influenza. Vaccination remains the most effective strategy to prevent severe disease and death, but its efficacy is reduced in older adults, particularly against influenza A(H3N2). The mechanisms underlying this age-related decline in vaccine-specific antibody responses remain unclear. We investigated the magnitude and quality of influenza-specific T-cell responses following quadrivalent inactivated influenza vaccination in adults...

CONCLUSIONS: Inclusion of fish in a healthy and balanced diet is associated with better white matter grades on MRI and slower progression of white matter hyperintensities and reduction of vascular-related lesions of the aging brain, suggesting a potential role in preventing neurocognitive deterioration. Heterogeneity across studies underscores the need for additional studies.

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Cellular senescence is defined as an irreversible growth arrest observed when cells are exposed to a variety of stressors, including DNA damage, oxidative stress, or nutrient deprivation. Although senescence is a well-established driver of aging and age-related diseases, it is a highly heterogeneous process with significant variations across organisms, tissues, and cell types. The relatively low abundance of senescent cells in healthy aged tissues poses a major challenge to the longitudinal...

Niemann-Pick disease type C (NPC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration, primarily caused by a functional defect in NPC1 resulting from gene mutations. NPC1, a lysosomal transmembrane protein, acts as a transporter of cholesterol from the lysosome to the endoplasmic reticulum, and its dysfunction results in the intracellular accumulation of unesterified cholesterol. Although microgliosis with accumulated cholesterol has been reported in NPC, the...

Emergency department (ED) length of stay (LOS) is associated with adverse outcomes and increases with age, but the extent to which this reflects differences beyond triage acuity is unclear. Emergency department (ED) length of stay (LOS) is associated with adverse outcomes and increases with age, but the extent to which this reflects differences beyond triage acuity is unclear.We conducted a retrospective cohort study of adult ED visits at a tertiary hospital in Hungary between 2016 and 2023 (n =...

Immunosenescence, the progressive aging of the immune system, is characterized by changes in immune cell composition and function that increase susceptibility to disease. However, how biological sex shapes immune aging at the cellular level remains poorly understood. Here, we analyze single-cell RNA sequencing data from the peripheral blood mononuclear cells of 982 female and male donors across adulthood. We find that aging drives sexually dimorphic compositional and transcriptional changes,...

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Several chemotherapeutics induce cancer cells to senescence, a persistent growth-arrest state associated with poor cancer prognosis. Relevant features in cancer cell biology, such as phenotypic plasticity and intercellular variability, are poorly understood for senescent cells (SnCs). This study examined the morphofunctional heterogeneity and dynamics of glioblastoma cells induced to senescence by Temozolomide (TMZ), focusing on pro-survival mechanisms, including autophagy and anti-apoptotic...

Changing family structures, nuclearization and urbanization are reshaping the socialization and support networks of older adults. Smaller families and migration reduce direct care and engagement opportunities, impacting health and functional ability in the growing aging population. The study explored social networks and perceived social support for older adults in rural and urban Chengalpattu, Tamil Nadu, through 33 in-depth interviews (22 older adults and 11 caregivers). Using the Convoy Model...