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China sets out to sample an unusual near-Earth asteroid
The target, flying in a rare quasi-satellite orbit, could be a piece of the Moon
Selective removal of astrocytic PERK protects against glymphatic impairment and decreases toxic aggregation of β-amyloid and tau
Dysfunction of the glymphatic system, a brain-wide waste clearance network, is strongly linked to Alzheimer's disease (AD) and the accumulation of β-amyloid (Aβ) and tau proteins. Here, we identify an astrocytic signaling pathway that can be targeted to preserve glymphatic function and mitigate neurotoxic protein buildup. Analysis of astrocytes from both human AD brains and two transgenic mouse models (5XFAD and PS19) reveals robust activation of the protein kinase RNA-like endoplasmic reticulum...
Miro1: A potential target for treating neurological disorders
The Miro1 protein is a member of the mitochondrial Rho GTPase (Miro) protein family and plays a crucial role in regulating the dynamic processes of mitochondria and participating in cellular movement and mitochondrial transport. In the nervous system, it ensures adequate energy supply for normal neuronal function and synaptic transmission. Additionally, Miro1 actively participates in the regulation of mitochondrial quality control and stress responses within neurons. Its primary function is to...
Advances in Alzheimer's therapy: Exploring neuropathological mechanisms to revolutionize the future therapeutic landscape
Alzheimer's disease (AD) is still an excessively complicated neurological disorder that impacts millions of individuals globally. The ideal defensive feature of the central nervous system (CNS) is the intimate junction of endothelial cells, which functions as a biological barrier to safely control molecular transport throughout the brain. The blood-brain barrier (BBB) comprises tightly locked astrocyte cell junctions on CNS blood capillaries. This biological barrier shields the brain from...
Convergent mapping of a tremor treatment network
Tremor occurs in various forms across diverse neurological disorders, including Parkinson's disease and essential tremor. While clinically heterogeneous, converging evidence suggests a shared brain network may underlie tremor across conditions. Here, we empirically define such a network using four modalities: lesion locations, atrophy patterns, EMG-fMRI, and deep brain stimulation outcomes. We show that network connectivity robustly explains clinical outcomes in independent cohorts undergoing...
Synapse vulnerability and resilience across the clinical spectrum of dementias
Preservation of synapses is crucial for healthy cognitive ageing, and synapse loss is one of the closest anatomical correlates of cognitive decline in Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia. In these conditions, some synapses seem particularly vulnerable to degeneration whereas others are resilient and remain preserved. Evidence has highlighted that vulnerability and resilience are intrinsically distinct phenomena linked to specific brain structural and/or...
Specific targeting of brain endothelial cells using enhancer AAV vectors
Brain endothelial cells (BECs) in brain vasculature are critical structural and functional components of the blood brain barrier (BBB). Adeno-associated virus (AAV) capsids have previously been genetically engineered to confer specificity to endothelial cells, but these capsids show limited endothelial cell specificity that varies by delivery conditions. We developed a set of new BEC-enhancer AAV vectors that specifically target BECs based on the cis-regulatory elements identified from...
Synapse vulnerability and resilience across the clinical spectrum of dementias
Preservation of synapses is crucial for healthy cognitive ageing, and synapse loss is one of the closest anatomical correlates of cognitive decline in Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia. In these conditions, some synapses seem particularly vulnerable to degeneration whereas others are resilient and remain preserved. Evidence has highlighted that vulnerability and resilience are intrinsically distinct phenomena linked to specific brain structural and/or...
Microglia conduct the symphony of white matter degeneration in aging through T cell recruitment
No abstract
An epigenetic clock for Xenopus tropicalis
DNA methylation clocks have been widely used for accurate age prediction, but most studies have been carried out on mammals. Here we present an epigenetic clock for the aquatic frog Xenopus tropicalis, a widely used model organism in developmental biology and genomics. To construct the clock, we collected DNA methylation data from 192 frogs using targeted bisulfite sequencing at genomic regions containing CpG sites previously shown to have age-associated methylation in Xenopus. We found highly...
Expanding the landscape of aging via orbitrap astral mass spectrometry and tandem mass tag integration
Aging results in a progressive decline in physiological function due to the deterioration of essential biological processes. While proteomics offers insights into aging mechanisms, prior studies are limited in proteome coverage and lifespan range. To address this, we integrate the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the proteomes of cortex, hippocampus, striatum and kidney in the C57BL/6JN mice, quantifying 8,954 to 9,376 proteins per...
Publisher Correction: Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis
No abstract
Translocation of gut bacteria promotes tumor-associated mortality by inducing immune-activated renal damage
Paraneoplastic syndrome represents severe and complex systemic clinical symptoms manifesting in multiple organs of cancer patients, but its cause and cellular underpinnings remain little explored. In this study, establishing a Drosophila model of paraneoplastic syndrome triggered by tumor transplantation, we found that the innate immune response, initiated by translocated commensal bacteria from a compromised intestine, significantly contributes to reduced lifespan in tumor-bearing hosts. Our...
Microglia activation orchestrates CXCL10-mediated CD8(+) T cell recruitment to promote aging-related white matter degeneration
Aging is the major risk factor for neurodegeneration and is associated with structural and functional alterations in white matter. Myelin is particularly vulnerable to aging, resulting in white matter-associated microglia activation. Here we used pharmacological and genetic approaches to investigate microglial functions related to aging-associated changes in myelinated axons of mice. Our results reveal that maladaptive microglia activation promotes the accumulation of harmful CD8^(+) T cells,...
IADL for identifying cognitive impairment in Chinese older adults: insights from cross-lagged panel network analysis
CONCLUSIONS: This study provides new insights into the associations between specific IADL activities and cognitive function domains among Chinese older adults. Concentrate on monitoring limitations related to "Use public transit," "Make food" and "Walk 1 km," and promoting broader life-space mobility may be beneficial to preventing the decline of cognitive function. The findings underscore the importance of targeting interventions not only by specific cognitive domains, but also potentially by...
Correction for Masliah et al., beta-Amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease
No abstract
Late Life Supplementation of 25-Hydroxycholesterol Reduces Aortic Stiffness and Cellular Senescence in Mice
Stiffening of the aorta is a key antecedent to cardiovascular diseases (CVD) with aging. Age-related aortic stiffening is driven, in part, by cellular senescence-a hallmark of aging defined primarily by irreversible cell cycle arrest. In this study, we assessed the efficacy of 25-hydroxycholesterol (25HC), an endogenous cholesterol metabolite, as a naturally occurring senolytic to reverse vascular cell senescence and reduce aortic stiffness in old mice. Old (22-26 months) p16-3MR mice, a...
Older Adults Without Family Caregivers Need Better Access to Medicaid Support Services
Changes to improve waiver access to adults aging solo.
Food-washing monkeys recognize the law of diminishing returns
Few animals have the cognitive faculties or prehensile abilities needed to eliminate tooth-damaging grit from food surfaces. Some populations of monkeys wash sand from foods when standing water is readily accessible, but this propensity varies within groups for reasons unknown. Spontaneous food-washing emerged recently in a group of long-tailed macaques (Macaca fascicularis) inhabiting Koram Island, Thailand, and it motivated us to explore the factors that drive individual variability. We...
Physical Activity Modifies the Metabolic Profile of CD4<sup>+</sup> and CD8<sup>+</sup> T-Cell Subtypes at Rest and Upon Activation in Older Adults
T-cell metabolism is a key regulator of immune function. Metabolic dysfunction in T cells from young mice results in an aged phenotype, accelerating immunosenescence. Physical activity (PA) maintains T-cell function and delays immunosenescence in older adults, but the underlying mechanisms are poorly understood. We investigated the effects of PA on the metabolic and functional profiles at a single-cell resolution of resting and stimulated T cells from young adults (N = 9, 23 ± 3 years) and...