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Great power and great responsibility: how consciousness changes the world
The contentious genius who made black holes real
How provinces and cities can sustain US–China climate cooperation
Selenoprotein P is a target for regulating extracellular vesicle biogenesis and secretion from activated microglia in vivo
Microglia, brain innate immune cells, participate in the spread of inflammatory signals and aggregated proteins through secretion of extracellular vesicles (EVs). Selenoprotein P (Sepp1) is a potential regulator of microglial EV secretion. Here, we investigate the effect of Sepp1 silencing on microglial transcriptomics to elucidate the Sepp1 regulatory mechanism of EV secretion and validate this effect in APP^(NL-G-F) knockin mice. Silencing of Sepp1 significantly reduces EV secretion and CD63...
Rlip76 in ageing and Alzheimer's disease: Focus on oxidative stress and mitochondrial mechanisms
RLIP76 (Rlip), a stress-responsive protein, plays a multifaceted role in cellular function. This protein acts primarily as a glutathione-electrophile conjugate (GS-E) transporter, crucial for detoxifying hazardous compounds and converting them into mercapturic acids. RLIP76 also modulates cytoskeletal motility and membrane plasticity through its role in the Ral-signaling pathway, interacting with RalA and RalB, key small GTPases involved in growth and metastasis. Beyond its ATP-dependent...
Retinopathy in Parkinson's disease: A potential biomarker for early diagnosis and clinical assessment
Parkinson's disease (PD) is a prevalent neurodegenerative disorder caused by degeneration of dopaminergic neurons, originating from the substantia nigra pars compacta, and characterized by motor symptoms such as bradykinesia, muscle rigidity, resting tremor, and postural instability, as well as non-motor symptoms such as anxiety, depression, reduced sense of smell, cognitive impairment, and visual dysfunction. Emerging evidence highlights the retina as a promising site for non-invasive...
Global trends and regional differences in mortality of cardiovascular disease and its impact on longevity, 1980-2021: Age-period-cohort analyses and life expectancy decomposition based on the Global Burden of Disease study 2021
CONCLUSION: Process in reducing CVD mortality contributed to longevity improvements over the past four decades globally, with expanded cardiovascular health disparities across various SDI regions. More attention should be paid to CVD epidemic in low SDI countries to mitigate regional inequalities.
Rlip76 in ageing and Alzheimer's disease: Focus on oxidative stress and mitochondrial mechanisms
RLIP76 (Rlip), a stress-responsive protein, plays a multifaceted role in cellular function. This protein acts primarily as a glutathione-electrophile conjugate (GS-E) transporter, crucial for detoxifying hazardous compounds and converting them into mercapturic acids. RLIP76 also modulates cytoskeletal motility and membrane plasticity through its role in the Ral-signaling pathway, interacting with RalA and RalB, key small GTPases involved in growth and metastasis. Beyond its ATP-dependent...
Immediate effects of structured and natural deep breathing on heart rate variability and blood pressure in community-dwelling older adults
CONCLUSIONS: This first direct comparison of structured versus natural DB in healthy older adults demonstrates that both approaches effectively enhance parasympathetic activity. These findings support DB as a cost-effective, accessible intervention for promoting autonomic balance in healthy aging, without requiring specialized equipment or instruction.
Long-term potentiation in the hippocampus: From magnesium to memory
Long-term potentiation (LTP) is a widely studied phenomenon since the underlying molecular mechanisms are widely believed to be critical for learning and memory and their dysregulation has been implicated in many brain disorders affecting cognitive functions. Central to the induction of LTP, in most pathways that have been studied in the mammalian CNS, is the N-methyl-D-aspartate receptor (NMDAR). Philippe Ascher discovered that the NMDAR is subject to a rapid, highly voltage-dependent block by...
Long-term potentiation in the hippocampus: From magnesium to memory
Long-term potentiation (LTP) is a widely studied phenomenon since the underlying molecular mechanisms are widely believed to be critical for learning and memory and their dysregulation has been implicated in many brain disorders affecting cognitive functions. Central to the induction of LTP, in most pathways that have been studied in the mammalian CNS, is the N-methyl-D-aspartate receptor (NMDAR). Philippe Ascher discovered that the NMDAR is subject to a rapid, highly voltage-dependent block by...
SenMayo transcriptomic senescence panel highlights glial cells in the ageing mouse and human retina
There is a growing need to better characterise senescent cells in the CNS and retina. The recently published SenMayo gene panel was developed to identify transcriptomic signatures of senescence across multiple organ systems, but the retina was not included. While other approaches have identified senescent signatures in the retina, these have largely focused on experimental models in young animals. We therefore conducted a detailed single-cell RNA-seq analysis to identify senescent cell...
Relationship between macronutrients and energy intake and liver serum transaminase levels in elderly athletes and non-athletes: findings from the Neyshabur longitudinal study on aging
CONCLUSIONS: This study revealed that higher calorie, protein, and carbohydrate intake were associated with elevated ALT and AST levels in elderly individuals, particularly athletes. For athletes, all three nutrients were linked to elevated ALT, while only carbohydrates and calories impacted AST. For non-athletes, only protein affected ALT. These findings suggest that tailored nutritional strategies may be necessary to preserve liver health in active aging populations.
The ultrastructural and proteomic analysis of mitochondria-associated endoplasmic reticulum membrane in the midbrain of a Parkinson's disease mouse model
Recent studies indicated that the dysregulation of mitochondria-associated endoplasmic reticulum membrane (MAM) could be a significant hub in the pathogenesis of Parkinson's disease (PD). However, little has been known about how MAM altered in PD. This study was aimed to observe morphological changes and analyze proteomic profiles of MAM in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. In MPTP-treated mice, transmission electron microscopy was applied for MAM...
Restoration of hair follicle inductive properties by depletion of senescent cells
Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells,...
An overview of the genes and biomarkers in Alzheimer's disease
Alzheimer's disease (AD) is the most common type of dementia and neurodegenerative disease characterized by neurofibrillary tangles (NFTs) and amyloid plaque. Familial AD is caused by mutations in the APP, PSEN1, and PSEN2 genes and these mutations result in the early onset of the disease. Sporadic AD usually affects older adults over the age of 65 years and is, therefore classified as late-onset AD (LOAD). Several risk factors associated with LOAD including the APOE gene have been identified....
Transcranial optogenetic brain modulator for precise bimodal neuromodulation in multiple brain regions
Transcranial brain stimulation is a promising technology for safe modulation of brain function without invasive procedures. Recent advances in transcranial optogenetic techniques with external light sources, using upconversion particles and highly sensitive opsins, have shown promise for precise neuromodulation with improved spatial resolution in deeper brain regions. However, these methods have not yet been used to selectively excite or inhibit specific neural populations in multiple brain...
Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits
Rare mutations in the gene encoding presenilin2 (PSEN2) are known to cause familial Alzheimer's disease (FAD). Here, we explored how altered PSEN2 expression impacts on the amyloidosis, endolysosomal abnormalities, and synaptic dysfunction observed in female APP knock-in mice. We demonstrate that PSEN2 knockout (KO) as well as the FAD-associated N141IKI mutant accelerate AD-related pathologies in female mice. Both models showed significant deficits in working memory that linked to elevated PSEN2...
Lifespan longitudinal changes in mesocortical thickness and executive function: Role of dopaminergic genetic predisposition
Dopamine (DA) signaling is critical for optimal cognitive aging, especially in prefrontal-parietal and fronto-striatal networks. Single nucleotide polymorphisms associated with dopamine regulation, COMTVal158Met and DRD2C957T, stand to exert influence on executive function performance via neural properties. The current study investigated whether longitudinal thinning of mesocortical regions is related to COMT and DRD2 genetic predisposition and associated with decline in executive function over...
An integrated single-cell atlas of blood immune cells in aging
Recent advances in single-cell technologies have facilitated studies on age-related alterations in the immune system. However, previous studies have often employed different marker genes to annotate immune cell populations, making it challenging to compare results. In this study, we combined seven single-cell transcriptomic datasets, comprising more than a million cells from one hundred and three donors, to create a unified atlas of human peripheral blood mononuclear cells (PBMC) from both young...