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Using cannabis edibles and alcohol together may make drivers far more impaired than either substance alone, according to new research from Johns Hopkins. Even more concerning, common field sobriety tests often failed to detect the cannabis-related impairment.

A sweeping global study found that chronic kidney disease now affects nearly 800 million people and has become one of the world's leading causes of death. Often silent in its early stages, the condition is also a major contributor to heart disease and may be even more common than current estimates suggest.

The brain must efficiently clear protein waste to maintain homeostasis, yet physiological drainage pathways remain poorly defined. Standard tracer injection approaches may not reflect endogenous efflux. Here, we develop a non-invasive genetic system to trace neuron-derived protein clearance from the brain to cerebrospinal fluid (CSF) and border tissues. We identify distinct drainage routes and border hotspots missed by tracer injection, confirmed by bioorthogonal labeling of endogenous neuronal...

The NLRP3 inflammasome contributes to a wide range of conditions from infections to Alzheimer's disease. NLRP3 forms an inactive decameric cage, that upon interaction with the trans-Golgi network (TGN) and microtubule organization center (MTOC), leads to inflammasome activation, yet whether non-decamer NLRP3 species form functional inflammasomes remains unclear. Here, we design a NLRP3 exon 3 deletion variant that forms low molecular weight NLRP3 assemblies. Spatially and dynamically highly...

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In Alzheimer's disease (AD), endogenous tau undergoes a pathogenic transition to form paired helical filaments (PHFs), but the cellular mechanisms driving this process have been elusive. Here, we identify the neuron-specific plasma membrane proteasome ('neuroproteasome') as a critical determinant of tau proteostasis. Selective inhibition of neuroproteasome function rapidly triggers the de novo formation of endogenous, sarkosyl-insoluble tau PHFs in primary neurons and mouse brain, which share...

H(2)O(2) functions as a signaling molecule regulating plant growth, development, and stress responses; however, its role in jasmonic acid (JA) signaling transduction and JA-regulated biological processes remains elusive. Here, we report that General regulatory factor 8 (GRF8) is a critical factor inhibiting JA signaling, while H(2)O(2) removes this inhibition to facilitate the JA response during root growth and leaf senescence in Arabidopsis. GRF8 interacts with and inhibits MYC2, the key...

Nearly all cellular processes are pH dependent. The acidic pH inside the lysosome (vacuole in yeast) is essential for cellular content degradation, signaling, and autophagy. Defects in lysosome/vacuole acidification are a conserved hallmark of aging and age-related diseases. Traditionally, the lysosome/vacuole is thought to import free protons (H⁺) from the surrounding neutral cytosol. Here, we uncovered a conserved lysosome/vacuole acidification mechanism from yeast to human involving...

Conventional bulk transcriptomic approaches obscure cellular and tissue-level heterogeneity critical to understanding age-related neurodegeneration. While single-cell transcriptomics resolved cellular identity, it sacrificed spatial context - a fundamental limitation for mechanistic disease understanding. Spatial transcriptomics emerges as a transformative technology that preserves native tissue architecture while enabling genome-wide transcriptome profiling at subcellular resolution,...

Human spaceflight exposes crew members to a combination of environmental stressors - including microgravity, galactic cosmic radiation, circadian disruption, and prolonged confinement - that together induce multisystem physiological changes resembling terrestrial aging. In this narrative review, we examine how short- and medium-term spaceflight affects all twelve recognized hallmarks of aging. Integrated multi-omics analyses in astronauts and rodent models identified mitochondrial dysfunction as...

Ageing is closely linked to cellular senescence, but this relationship remains incompletely defined. Although many studies have reported age-associated increases in senescence markers, no review has systematically integrated the available quantitative data across tissues and species to clarify how senescence-associated cell populations change with age. In addition, the field has often used inconsistent definitions for intermediate and senescent states, making cross-study interpretation...

CONCLUSION: Low STS power showed a stronger association with low UGS than low handgrip strength in male. However, their overall impact on functional ability and mortality was similar between muscle function measures in older male and female.

Aging is associated with chronic low-grade inflammation, which is thought to contribute to both cognitive decline and various neurodegenerative diseases. Cannabinoids are reported to reduce levels of inflammatory markers; however, these effects have not been thoroughly assessed in older subjects. To address this gap, we evaluated the effects of sub-chronic cannabis smoke exposure on serum and brain inflammatory markers in younger and older mice. Younger (4 month old) and older (22 month old)...

During aging, the progressive decline in neuronal function contributes to cognitive impairment and predisposes individuals to neurodegenerative disorders. This phenomenon has become increasingly prominent in modern society. Recent studies have found that post-translational modifications (PTMs) of proteins play a crucial role in the aging process, influencing the physiological functions and pathological changes in brain cells. This article reviews the variety and complexity of PTMs across brain...

Dual hole transport layers consisting of NiO(x) and self-assembled molecules are widely adopted in inverted perovskite solar cells, yet plagued by high impurity content, inefficient hole transport, low molecular coverage, weak interfacial binding, unstable buried interface and energy level mismatch. Herein, a low-temperature chemical precipitation strategy is developed to synthesize high-quality NiO(x) nanoparticles as hole transport layers. Compared with the room-temperature route, the...

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Hematopoietic stem cells (HSCs) transition through different functional states throughout life from emergence and expansion in the fetus, homeostasis maintenance in adulthood, and progressive functional decline with age. Aged HSCs are characterized by increased phenotypic number, decreased self-renewal and long-term reconstitution capacity, myeloid-biased differentiation, and clonal hematopoiesis. In this review, we summarize the life cycle of HSCs, integrate recent advances in understanding the...

Chronic inflammation and aging skew hematopoiesis toward myelopoiesis at the expense of lymphoid output. We screened type 2 and anti-inflammatory cytokines to identify extrinsic signals capable of restoring lymphoid lineage commitment in hematopoietic stem and progenitor cells (HSPCs). Interleukin 4 (IL-4) specifically inhibited inflammation-induced myelopoiesis and shifted multipotent progenitor (MPP) differentiation toward the lymphoid lineage. IL-4 activated a signal transducer and activator...

CONCLUSION: BDNF, FABP-3, OSM and OSTN contributed to a stepwise regression model predicting the FI after adjusting for age, whereas only SPARC remained in a model predicting FP score.

Ageing heterogeneity hampers prevention and care. We used routine biochemical panels and unsupervised learning to identify latent phenotypes in community-dwelling older adults. In 1491 participants from the Toledo Study for Healthy Ageing (TSHA) with ~10-11 years of follow-up, 39 blood biomarkers were dimension-reduced and clustered, yielding three phenotypes: Healthy, Metabolic (subclinical dysmetabolism), and Haematological (low erythroid/renal profile). Phenotypes differed in functional...