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CONCLUSIONS: Among older adults in China, lifestyles only mediate a small proportion of frailty disparities in overall survival; consequently, without direct interventions for frailty or additional favorable measures, promoting healthy lifestyles alone is insufficient to significantly reduce frailty disparities in survival. Furthermore, individuals of frailty and unhealthy lifestyles experience significantly shorter survival, highlighting the urgent need for targeted interventions for this...

CONCLUSION: This study offers a culturally nuanced understanding of AIP, challenging the notion that 'place' is solely a physical or geographical location. It highlights the significance of social connectedness, emotional security, digital participation, and the desire to avoid institutional care. These findings provide valuable insights for policymakers and practitioners, underscoring the need to design ageing policies and care practices that address not only physical housing but also social...

Sophisticated bots risk contaminating surveys, games, and other approaches designed to shed light on human behavior

During deep co-evolution of viruses and host cells, viruses have selected specific host cellular proteins redirected from physiological functions to viral needs, thereby disturbing cellular proteostasis and increasing the risk of triggering protein misfolding diseases (PMDs). Identifying virus-specific, repurposed host proteins also allows the study of fundamental cellular events in "sporadic" PMDs, independent of the virus. Here, we identify a small molecule with very strong activity against...

Parkinson's disease (PD) patients show gait and motor timing impairments that can be improved with different behavioral therapies. This study involved an intervention with seventeen PD patients utilizing a pre-training-training-post-training protocol. The experimental paradigm included a march-in-place task (MPT) and an auditory synchronization-continuation stepping task (SCT). During these tasks, their foot movements were tracked with an infrared motion-capture system. In addition, patients...

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which is associated with changes in microglia function. While age remains the biggest risk factor, the underlying molecular cause of PD onset and its concurrent neuroinflammation are not well understood. Many identified PD risk genes have been directly linked to dopamine neuron impairment, while others are linked to immune cell function. In this study, we found that the PD...

Black rice diets are enriched with unsaturated fatty acids that are thought to be beneficial for neurodegenerative disorders in aging. Here we find that α-linolenic acid (ALA) and 11,14-eicosadienoic acid (EDA), which are naturally enriched in black rice, inhibit amyloid pathology, rescue cognition and extend lifespan in mouse preclinical models of Alzheimer's disease via allosteric activation of G protein-coupled receptor 120 (GPR120) in plaque-associated macrophages and activated microglia. We...

Progressive neuronal loss and brain atrophy are principal determinants of cognitive decline in Alzheimer's disease (AD), yet most mouse models fail to recapitulate these features. Here we identify cyclin-dependent kinase 3 (CDK3) as a key driver of neurodegeneration in AD. CDK3 is elevated in human AD brains and correlates with disease severity. As laboratory mice carry a nonfunctional Cdk3 mutation, we generated two models with restored CDK3 activity and then crossed to AD backgrounds. Both...

With therapeutic progress in Alzheimer's disease (AD), more molecular and mechanistic targets are coming into focus. Beyond amyloid, emerging targets include tau, neuroinflammation and neurotransmitters. Targeting neuroinflammation in neurodegenerative diseases has been explored using cyclooxygenase inhibitors, but it has mostly been unsuccessful. Among the drug classes under investigation for AD are the glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are approved for the treatment...

We previously established distinct roles for the transcriptional elongation factors PAF1, negative elongation factor (NELF), SPT4/5, and SPT6 using auxin-inducible degron systems in human cell lines. Here, we integrate long- and short-read RNA-seq data from these degron lines to quantify transcript isoform usage at single-molecule resolution, identifying elongation factor-specific RNA processing regulons, including a cellular senescence-enriched regulon impacted by NELF and SPT6. Long-term NELF...

Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators driving cancer development and potential therapeutic targets across multiple human malignancies. However, their mechanistic roles during head and neck squamous cell carcinoma (HNSCC) initiation and progression remain incompletely elucidated. Here, we identified a novel oncogenic lncRNA, LINC00973, which was aberrantly upregulated in clinical samples and associated with aggressive clinicopathological features and adverse clinical...

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which is associated with changes in microglia function. While age remains the biggest risk factor, the underlying molecular cause of PD onset and its concurrent neuroinflammation are not well understood. Many identified PD risk genes have been directly linked to dopamine neuron impairment, while others are linked to immune cell function. In this study, we found that the PD...

Aging clocks use machine learning to estimate biological age as a proxy for general health state. Here, we critically examine their practical value, highlighting fundamental challenges: abstract definitions, inconsistent clinical validation, and ignored prediction uncertainty. By comparing aging clocks with expert risk scores, direct outcome predictors, and emerging large health models, we question their benefits and encourage researchers to explicitly justify clock advantage over established...

Black rice diets are enriched with unsaturated fatty acids that are thought to be beneficial for neurodegenerative disorders in aging. Here we find that α-linolenic acid (ALA) and 11,14-eicosadienoic acid (EDA), which are naturally enriched in black rice, inhibit amyloid pathology, rescue cognition and extend lifespan in mouse preclinical models of Alzheimer's disease via allosteric activation of G protein-coupled receptor 120 (GPR120) in plaque-associated macrophages and activated microglia. We...

Normal aging triggers substantial topological transformation within resting-state electroencephalography (rs-EEG) networks. Given that the small-world (SW) architecture of hemispheric EEG networks may reflect an evolutionarily and developmentally optimized organization, investigating their modulations with age offers critical insights into the dynamic reorganization of functional connectivity (FC) patterns throughout adulthood. Utilizing rs-EEG data from a single-site public repository collected...

CONCLUSIONS: This large-scale study reveals a substantial burden of dementia in the studied Iranian provinces. The identified risk factors, including female sex, advanced age, widowhood, and low education, highlight vulnerable subgroups and underscore the urgent need for targeted public health strategies focused on early detection, risk reduction, and support systems for the elderly in Iran.

Centrifugation of biological matter in density gradient solutions is a standard method for separating cell types or components. It is also used to separate red blood cells (RBCs) by age, as they lose water and become denser over their lifespan. When the density gradient is prepared with Percoll, discrete bands of RBCs are systematically observed along the gradient, despite the continuous density distribution of RBCs. Early studies suggested that cell aggregation might influence spatial...

Aging disrupts intestinal stem cell (ISC) lineage fidelity, impairing epithelial barrier function and then promoting systemic health decline. In this study, we identify peroxisomal dysfunction as a critical driver of age-associated ISC mis-differentiation. Using Drosophila and mouse colonic organoids, we demonstrate that reduced PEX5 expression in aged ISCs impairs peroxisomal matrix protein import, leading to very long-chain fatty acids (VLCFAs) accumulation. In addition, we found that...

Topoisomerase III-beta (Top3b) reduces nucleic acid torsional stress and intertwining generated during RNA and DNA metabolism while protecting the genome from pathological R-loops, which otherwise result in DNA breakage and genome instability. By studying Top3b knockout mice (Top3b-KO), we find that the loss of Top3b accelerates the development of spontaneous atypical lymphoid hyperplasia and lymphomas arising in spleens and lymph nodes, organs with prominent Top3b expression. Aging Top3b-KO...

In a game of visual telephone, models converge on ecstatic sports wins, romantic nights in Paris, and other cultural chestnuts