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Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity and gradual electrochemical maturation

6 months 3 weeks ago
Medial ganglionic eminence-derived inhibitory γ-aminobutyric acid (GABAergic) pallial interneurons (MGE-pINs) are essential regulators of cortical circuits, and their dysfunction is associated with neurological disorders. We developed human MGE-pINs from pluripotent stem cells for the treatment of drug-resistant epilepsy. Here, we analyzed xenografted MGE-pINs from human pluripotent stem cells (hMGE-pINs) over the lifespan of host mice in healthy and epileptic environments using single-nuclei...
Marina Bershteyn

Microglia-neuron crosstalk in Alzheimer's disease: an exploration of molecular mechanisms and pathological implications

6 months 3 weeks ago
Microglia, the resident immune sentinels of the central nervous system (CNS), engage in dynamic crosstalk with neurons, the principal units of information transmission, to maintain CNS homeostasis. Emerging research has established that dysregulation of this intricate communication network critically contributes to Alzheimer's disease (AD) pathogenesis, offering novel insights for therapeutic development. In this review, we dissect the molecular mechanisms underlying multifaceted...
Xizhen Kang

The Transcriptome Trajectory Reveals Sex- and Age-Dependent Changes in the Mouse Adrenal Gland

6 months 3 weeks ago
In both humans and mice, the adrenal gland is a sexually dimorphic organ, but the extent of this diversity throughout development remains unclear. Here, we analyzed the mouse adrenal gland transcriptome at postnatal days 0, 7, 15, 21, 28, 35, and 49 to uncover its transcriptomic trajectory. Sex-dependent differences, indicated by the number of differentially expressed genes, gradually increase over time. Two Y-linked genes are consistently expressed in male adrenal glands, suggesting that...
Hui Wang

Effects of aging on gene expression networks in the Drosophila genetic reference panel

6 months 3 weeks ago
The genetic basis of naturally occurring variation in organismal senescence and lifespan remains largely unknown. We quantified genome-wide gene expression levels of young and 3-week-old flies of the Drosophila Genetic Reference Panel and performed a systems genetics analysis integrating genomic, transcriptomic, and organismal phenotype variation. Aging had widespread but small effects on nearly the entire transcriptome, which were dependent on the genetic background. Although the co-expression...
Suxu Tan

Human stem cell-derived GABAergic interneuron development reveals early emergence of subtype diversity and gradual electrochemical maturation

6 months 3 weeks ago
Medial ganglionic eminence-derived inhibitory γ-aminobutyric acid (GABAergic) pallial interneurons (MGE-pINs) are essential regulators of cortical circuits, and their dysfunction is associated with neurological disorders. We developed human MGE-pINs from pluripotent stem cells for the treatment of drug-resistant epilepsy. Here, we analyzed xenografted MGE-pINs from human pluripotent stem cells (hMGE-pINs) over the lifespan of host mice in healthy and epileptic environments using single-nuclei...
Marina Bershteyn

Central and Bridging Roles of Social Relationships Within the Multilayer Health Ecology Model in Motoric Cognitive Risk Syndrome: A Network Analysis

6 months 3 weeks ago
CONCLUSIONS AND IMPLICATIONS: Social networks, social activities, and social support function as central and bridging roles within the multilayer health ecology model, linking socioeconomic and behavioral factors in MCR. These findings underscore the importance of social relationships as culturally sensitive and modifiable targets for multilevel interventions from a mechanistic perspective, offering a theoretical foundation for practices and policies aimed at slowing MCR progression and...
Liming Su

Effects of Social Learning Theory-Based Training on Pressure Injury Competence in Chinese Nursing Home Assistants: A Cluster RCT

6 months 3 weeks ago
CONCLUSIONS AND IMPLICATIONS: A social learning theory-based training program can effectively enhance nursing assistants' pressure injury prevention and management competence; however, visual identification skill retention requires reinforcement. This scalable, theory-driven model addresses global workforce training gaps in long-term care, offering actionable strategies to reduce pressure injury incidence and improve care quality for aging populations.
Yanxia Guo

Decoding DNA repair regulation across human lifespan variability

6 months 3 weeks ago
DNA repair, an evolutionarily conserved mechanism essential for restoring genetic homeostasis, has been implicated in aging and longevity by multiple lines of evidence. However, due to the challenges in obtaining human research materials, studies on the interplay between DNA repair and aging rely primarily on laboratory animal models, whose regulatory mechanisms may not fully mirror those in humans. Strikingly, the rate of aging varies by nearly an order of magnitude across humans, ranging from...
Yunjia Tang

Apheresis for Senescence: Targeting the Senescence-associated Secretory Phenotype to Delay Aging and Age-Related Diseases

6 months 3 weeks ago
Aging is driven by cellular senescence and chronic inflammation, largely mediated by the senescence-associated secretory phenotype (SASP). SASP factors promote inflammaging, impair tissue homeostasis, and contribute to age-related diseases such as cardiovascular disease, neurodegeneration, and cancer. Current anti-aging strategies focus on senolytics or SASP inhibitors, yet these approaches have limitations. We discuss therapeutic plasma exchange (TPE) and selective apheresis, as interventions...
Yamac Akgun

The role of chondrocyte senescence in osteoarthritis pathogenesis and therapeutic implications

6 months 3 weeks ago
Osteoarthritis (OA) is a common and debilitating joint disorder, with its pathogenesis significantly influenced by factors such as aging and obesity. A critical aspect of OA development is the senescence of chondrocytes, which is characterized by irreversible cell cycle arrest and the secretion of pro-inflammatory molecules, collectively known as the senescence-associated secretory phenotype (SASP). Senescent chondrocytes compromise the maintenance of the extracellular matrix (ECM) and...
Kai Huang

Improved mRNA-based RSV vaccine with PreF forming enveloped virus-like particles

6 months 3 weeks ago
Respiratory syncytial virus (RSV) causes severe respiratory disease in infants and the elderly. However, natural infection fails to induce durable immune protection, and existing mRNA vaccines for older adults exhibit limited long-term efficacy. We developed an antigen engineering strategy inserting ESCRT/ALIX-binding region (EABR) into truncated RSV prefusion F (PreF) cytoplasmic tails to form enveloped virus-like particles (eVLPs). In murine models, PreF-EABR mRNA vaccines elicited higher,...
Pengdi Chai

Disability Among Middle Aged and Older Immigrants: Differences by Citizenship, English Proficiency, and Years in United States

6 months 3 weeks ago
ObjectivesUnited States (U.S.) immigrants are rapidly aging, although little is known on how acculturation influences their disability risk.MethodsWe pooled 2000-2018 data (n = 50,075) from the National Health Interview Survey (NHIS) to examine odds of activities of daily living (ADL) disability among middle aged (40-64) and older (65+) immigrants based on three acculturation indicators while accounting for various measures.ResultsAmong middle aged immigrants, citizenship was associated with...
Shane D Burns

Burst firing in Alzheimer's disease: A shift beyond amyloid?

6 months 3 weeks ago
In this issue of Cell, Harris et al. reveal that high-molecular-weight soluble tau-rather than amyloid-beta-impairs burst firing in hippocampal neurons, providing a mechanistic link to cognitive decline in Alzheimer's disease. This disruption, linked to CaV2.3 downregulation, highlights soluble tau as a key driver of neuronal dysfunction and a promising therapeutic target.
Luísa V Lopes

Epigenetic age is associated with regional brain aging along the sensorimotor-to-association axis of cortical organization

6 months 3 weeks ago
Brain age and epigenetic age (DNAmAge) are 'biological clocks' independently linked to health outcomes. However, the relationship between brain and epigenetic age remains unclear. We used path analysis to investigate relationships between chronological age, DNAmAge, and brain age and explored whether advanced aging in specific brain regions relates to DNAmAge. BrainAge (global and regional) was estimated from brain MRI in 149 participants (ages 20-80). From whole blood, four DNAmAges were...
Nicholas Riccardi