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Scientists found a cannabis compound that relieves pain without the high

2 weeks 3 days ago
Compounds responsible for the aroma of cannabis and many other plants may offer a surprising new way to relieve chronic pain. Researchers found that several cannabis-derived terpenes significantly reduced pain in mouse models of fibromyalgia and post-surgical pain, with one terpene, geraniol, showing especially strong effects. Unlike THC, these compounds are not associated with psychoactive effects, making them a potentially attractive alternative for pain treatment.

This DNA repair gene went rogue and exposed a cancer weakness

2 weeks 3 days ago
Scientists have discovered that a gene normally considered a DNA-protecting "good guy" can become dangerous when cells make too much of it. The gene, EXO1, acts like molecular scissors that help repair DNA, but when overproduced it starts cutting DNA it shouldn't, creating damage linked to cancer.

RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis

2 weeks 3 days ago
Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and...
Qunhua Han

Analysis of second-generation epigenetic clocks reveals further associations between disproportionate biological ageing and hippocampal volume

2 weeks 3 days ago
Age acceleration, or the difference between biological and chronological age, is a research area of growing interest, particularly in the field of age-related and neurodegenerative disorders, including Alzheimer's disease (AD). First-generation epigenetic clocks that predict chronological age utilising DNA methylation data were the first to derive estimates of age acceleration, which have been associated with several age-related conditions. More recently, second-generation epigenetic clocks that...
Lidija Milicic

A local-to-distant shift in dynamic brain connectivity marks early Alzheimer's risk

2 weeks 3 days ago
Alzheimer's disease (AD) involves early disruptions in brain connectivity, yet how AD risk markers relate to resting-state dynamic functional connectivity (rs-dFC) remains unclear. We examined associations of AD pathology, genetic risk, and blood-based biomarkers (BBMs) of neurodegeneration with local and distant rs-dFC in cognitively normal older adults and explored links with cognitive performance. Baseline data from 86 cognitively normal older adults in the AGUEDA trial (NCT05186090) were...
Andrea Coca-Pulido

Telomere length and appendicular lean mass over six years in older adults with overweight or obesity and metabolic syndrome: a prospective cohort study

2 weeks 3 days ago
Telomere length (TL) has been proposed as a marker of appendicular lean mass (ALM) decline; however, longitudinal evidence remains limited. We aimed to investigate the longitudinal association between TL and 6-year trajectories of ALM. This longitudinal study included 185 older adults aged 55-75 years with overweight or obesity and metabolic syndrome at baseline. Baseline TL was assessed using a monochrome multiplex real-time quantitative PCR. ALM from the four limbs was obtained at baseline,...
Héctor Vázquez-Lorente

Dual blockade of PD-1 and NKG2A prevents NK cell senescence and reprograms the immunosuppressive microenvironment in pancreatic cancer

2 weeks 3 days ago
Immune checkpoint blockade (ICB) shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that ICB-induced IFN-γ signaling upregulates H2-T23 on pancreatic tumor cells, which interacts with NKG2A on NK cells to induce NK cell senescence through activation of p38 MAPK and STAT1/3 pathways. This impairs NK cell cytotoxicity and restricts antitumor immunity. Dual blockade of PD-1 and NKG2A effectively prevents NK cell senescence, restores NK cell function, and...
Yu Zhang

Review of current research practices in social and structural determinants of health data collection in Canadian longitudinal cohorts of aging and dementia

2 weeks 3 days ago
CONCLUSION: SSDH that shape dementia risk and brain resilience, many modifiable at the community and policy levels, remain unevenly collected in Canadian aging and dementia cohorts. Strengthening and harmonizing SSDH measurement is a critical step toward equitable dementia prevention and reducing health disparities.
Stefanie A Tremblay

Dynamic heterogeneity in the self-induced spin glass state of elemental neodymium

2 weeks 3 days ago
Spin glasses are magnetic materials exhibiting numerous magnetization patterns, that randomly vary both in real space and in time. To date, it is still not well understood what the nature of these spatiotemporal dynamics is, namely if they are completely random or if there are relevant and correlated length and time scales. Here, we demonstrate dynamic heterogeneity in the aging dynamics of elemental neodymium. We used spin-polarized scanning tunneling microscopy in combination with atomistic...
Lorena Niggli

Integrated proteomic and metabolomic analyses implicate redox-metabolic pathways in PTSD-associated multisystem disease and accelerated aging

2 weeks 3 days ago
Posttraumatic stress disorder (PTSD) is associated with increased risk of chronic disease and premature aging, yet underlying molecular mechanisms remain unclear. We performed plasma proteomics (SomaScan; 9404 proteins) and targeted metabolomics (145 metabolites) in 393 World Trade Center responders (232 with PTSD, 161 trauma-exposed controls). A total of 114 proteins and seven metabolites were differentially expressed in PTSD. Top proteins included NCAN, BCAN, NCAM1, and GDF15. Top metabolites...
Pei-Fen Kuan

Investigating the human anellome across the lifespan reveals sex-specific biphasic trajectories

2 weeks 3 days ago
Anelloviruses dominate the human plasma virome, yet their lifespan dynamics and relationships with the immune system are unclear. We integrated metagenomics with cytokines, HERV-K, and CMV profiling across 405 individuals (0-100 years) and found that prevalence, abundance, and diversity varied non-linearly with age and by sex. Alphatorqueviruses accumulated progressively with age, while betatorqueviruses and gammatorqueviruses displayed biphasic, female-specific patterns. Alphatorquevirus...
Yakhouba Kane

Coordinated transcriptional shifts in microglia and oligodendrocytes from neurodevelopment to inflammaging

2 weeks 3 days ago
Glial cells shape brain development and aging, yet whether distinct glial lineages undergo coordinated lifespan transitions remains unclear. Although microglial aging states and oligodendrocyte vulnerability in neurodegeneration are well described, it remains unclear whether these programs evolve independently or in a temporally related manner. Here, we analyzed Mouse Cell Atlas single-cell RNA-seq data spanning embryogenesis to 24 months. Microglia and oligodendrocytes were the most...
Yi-Shian Peng

Molecular crosstalk between MAPK signaling and neuroprotective pathways in Parkinson's disease: from pathogenesis to therapeutic potential

2 weeks 4 days ago
Mitogen-activated protein kinase (MAPK) signaling is increasingly recognized as a central regulator in the pathogenesis of Parkinson's disease (PD). PD is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), driven by a complex interplay of mitochondrial dysfunction, oxidative stress, and neuroinflammation. While basal MAPK activity is essential for neuroprotection and neuronal growth, its overactivation,...
Manar G Shalabi

Disruption of the brain-spleen axis impairs monocyte-microglia communication and accelerates disease progression in a mouse model of amyloidosis

2 weeks 4 days ago
Alzheimer's disease (AD) is characterized by a prolonged asymptomatic phase before cognitive decline emerges, yet the mechanisms driving symptom onset remain unclear. Here, we hypothesized that the transition from asymptomatic to symptomatic disease is linked to dysfunction of brain-immune communication. Retrograde neuronal tracing in the 5xFAD mouse model of amyloidosis reveals reduced brain-spleen connectivity at advanced disease stages. To probe the functional role of the brain-spleen axis in...
Tommaso Croese

Single-cell profiling of DNA methylation in autism spectrum disorder prefrontal cortex reveals distinct regulatory and aging signatures

2 weeks 4 days ago
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. Studies of postmortem ASD brain tissue have revealed convergent molecular changes across the cortex. Whether these features are reflected in cell-type-specific epigenetic signatures is unknown. Here, we present a single-cell analysis of DNA methylation (DNAm) coupled with transcriptomics in ASD. Using snmCT-seq, we profiled DNAm and transcript levels from over 60,000 nuclei derived from the prefrontal cortex of 49...
Katherine W Eyring