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Scientists uncover hearth Neanderthals may have used to make tar
Researchers re-create process of burning branches to make tarry adhesive to haft stone tools
China poised to turn on one of world’s most powerful sources of x-ray light
Beams from $657 million next-generation synchrotron will reveal atomic-scale structure of proteins and materials
‘I’m really shocked.’ Children not being vaccinated for mpox in Congo
Regulatory and liability issues are delaying immunization of the most vulnerable group
Elected to the House, veteran high school science teacher urges ‘evidence-based’ decision-making
Democrat John Mannion flips New York district with plea for bipartisanship
HLA is a potent immunoinflammatory target in asymptomatic Alzheimer's disease
Alzheimer's disease (AD) is a common neurodegenerative disease, neuroinflammation is an early pathological feature of AD. However, the alteration of the immune microenvironment in asymptomatic AD was not fully explained. In this study, we aimed to utilize the transcriptome data of AD patients in public databases to reveal the change of immune microenvironment in asymptomatic AD and screen the potential drug targets. A series of bioinformatics analyses were done, including differentially...
Whole-genome sequencing to identify rare variants in East Asian patients with dementia with Lewy bodies
Dementia with Lewy bodies (DLB) is the second most common form of age-related dementia, following Alzheimer's disease (AD). DLB is associated with a worse prognosis than AD and is characterized by a more rapid progression of cognitive impairment and a poorer quality of life. In addition, the pathogenesis of DLB is less understood than that of AD, and only three genes-SNCA (α-synuclein), APOE (apolipoprotein E), and GBA1 (glucosylceramidase beta 1)-have been convincingly demonstrated to be...
New schizophrenia drug could treat Alzheimer's disease
No abstract
Exome sequencing in Asian populations identifies low-frequency and rare coding variation influencing Parkinson's disease risk
Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in...
Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease
The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron...
Diets to promote healthy brain ageing
Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical...
Cross-sectional and longitudinal relationships among blood-brain barrier disruption, Alzheimer's disease biomarkers, and cognition in cognitively normal older adults
Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer's disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships...
Age-Related Hearing Loss: A cross-sectional study of healthy older Australians
Introduction Hearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing...
Nutrient control of growth and metabolism through mTORC1 regulation of mRNA splicing
Cellular growth and organismal development are remarkably complex processes that require the nutrient-responsive kinase mechanistic target of rapamycin complex 1 (mTORC1). Anticipating that important mTORC1 functions remained to be identified, we employed genetic and bioinformatic screening in C. elegans to uncover mechanisms of mTORC1 action. Here, we show that during larval growth, nutrients induce an extensive reprogramming of gene expression and alternative mRNA splicing by acting through...
Sarcopenia and the biological determinants of aging: A narrative review from a geroscience perspective
BACKGROUND: The physiopathology of sarcopenia shares common biological cascades with the aging process, as does any other age-related condition. However, our understanding of the interconnected pathways between diagnosed sarcopenia and aging remains limited, lacking sufficient scientific evidence.
Differentiated and mature neurons are more responsive to neurotoxicant exposure at both transcriptional and translational levels
SH-SY5Y human neuroblastoma cells have been extensively used as an in vitro model system in a diverse range of studies involving neurodevelopment, neurotoxicity, neurodegeneration, and neuronal ageing. Both naïve and differentiated phenotypes of SH-SY5Y cells are utilized to model human neurons under in vitro conditions. The process of differentiation causes extensive remodeling of neuronal cells at multiple omic levels, including the epigenome and proteome. In the present investigation, the...
mTORC1, the maestro of cell metabolism and growth
The mechanistic target of rapamycin (mTOR) pathway senses and integrates various environmental and intracellular cues to regulate cell growth and proliferation. As a key conductor of the balance between anabolic and catabolic processes, mTOR complex 1 (mTORC1) orchestrates the symphonic regulation of glycolysis, nucleic acid and lipid metabolism, protein translation and degradation, and gene expression. Dysregulation of the mTOR pathway is linked to numerous human diseases, including cancer,...
Exome sequencing in Asian populations identifies low-frequency and rare coding variation influencing Parkinson's disease risk
Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in...
Diets to promote healthy brain ageing
Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical...
Residual microglia following short-term PLX5622 treatment in 5xFAD mice exhibit diminished NLRP3 inflammasome and mTOR signaling, and enhanced autophagy
While moderately activated microglia in Alzheimer's disease (AD) are pivotal in clearing amyloid beta (Aβ), hyperactivated microglia perpetuate neuroinflammation. Prior investigations reported that the elimination of ~80% of microglia through inhibition of the colony-stimulating factor 1 receptor (CSF1R) during the advanced stage of neuroinflammation in 5xFamilial AD (5xFAD) mice mitigates synapse loss and neurodegeneration. Furthermore, prolonged CSF1R inhibition diminished the development of...
Loss of Earth's old, wise, and large animals
Earth's old animals are in decline. Despite this, emerging research is revealing the vital contributions of older individuals to cultural transmission, population dynamics, and ecosystem processes and services. Often the largest and most experienced, old individuals are most valued by humans and make important contributions to reproduction, information acquisition and cultural transmission, trophic dynamics, and resistance and resilience to natural and anthropogenic disturbance. These...