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Should India expand push for gas stoves? Health study finds few benefits, complicating picture
Nation has been trying to phase out smoky traditional stoves that burn wood and dung
Polar bear fur has a built-in deicing feature
An analysis of the Arctic animals’ fur reveals chemical clues to how they stay ice-free
Banished from world’s biggest physics lab, Russian scientists look inward—and to China
Breakdown of collaboration with CERN forcing many physicists to reorient work
Analysis of TEM micrographs with deep learning reveals APOE genotype-specific associations between HDL particle diameter and Alzheimer's dementia
High-density lipoprotein (HDL) particle diameter distribution is informative in the diagnosis of many conditions, including Alzheimer's disease (AD). However, obtaining an accurate HDL size measurement is challenging. We demonstrated the utility of measuring the diameter of more than 1,800,000 HDL particles with the deep learning model YOLOv7 (you only look once) from micrographs of 183 HDL samples, including patients with dementia or normal cognition (controls). This method was shown to be more...
Diverse pathways for the treatment of Parkinson's disease: Integration and development of traditional and emerging therapies
Parkinson's disease (PD) is the second most common central neurodegenerative disease in the world after Alzheimer's disease (AD), which mainly occurs in middle-aged and elderly people, and is increasing with the aging of the population. With the increasing incidence of PD, it is particularly important to explore its pathology and provide effective interventions and treatments. The pathogenesis of PD involves a variety of factors such as genetics, environment, and age, and is not yet fully...
Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease
Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, most of the disease heritability has yet to be uncovered, suggesting that there is substantial genetic risk conferred by other forms of genetic variation. There are over one million short tandem repeats (STRs) in the genome, and their link to AD risk has not been assessed. As pathogenic expansions of STR cause over 30 neurologic diseases, it is important...
Network segregation during episodic memory shows age-invariant relations with memory performance from 7 to 82 years
Lower episodic memory capability, as seen in development and aging compared with younger adulthood, may partly depend on lower brain network segregation. Here, our objective was twofold: (1) test this hypothesis using within- and between-network functional connectivity (FC) during episodic memory encoding and retrieval, in two independent samples (n = 734, age 7-82 years). (2) Assess associations with age and the ability to predict memory comparing task-general FC and memory-modulated FC. In a...
Biomolecular condensates in immune cell fate
Fate decisions during immune cell development require temporally precise changes in gene expression. Evidence suggests that the dynamic modulation of these changes is associated with the formation of diverse, membrane-less nucleoprotein assemblies that are termed biomolecular condensates. These condensates are thought to orchestrate fate-determining transcriptional and post-transcriptional processes by locally and transiently concentrating DNA or RNA molecules alongside their regulatory...
Analysis of TEM micrographs with deep learning reveals APOE genotype-specific associations between HDL particle diameter and Alzheimer's dementia
High-density lipoprotein (HDL) particle diameter distribution is informative in the diagnosis of many conditions, including Alzheimer's disease (AD). However, obtaining an accurate HDL size measurement is challenging. We demonstrated the utility of measuring the diameter of more than 1,800,000 HDL particles with the deep learning model YOLOv7 (you only look once) from micrographs of 183 HDL samples, including patients with dementia or normal cognition (controls). This method was shown to be more...
Diverse pathways for the treatment of Parkinson's disease: Integration and development of traditional and emerging therapies
Parkinson's disease (PD) is the second most common central neurodegenerative disease in the world after Alzheimer's disease (AD), which mainly occurs in middle-aged and elderly people, and is increasing with the aging of the population. With the increasing incidence of PD, it is particularly important to explore its pathology and provide effective interventions and treatments. The pathogenesis of PD involves a variety of factors such as genetics, environment, and age, and is not yet fully...
Enhancing immunity during ageing by targeting interactions within the tissue environment
Immunity declines with age. This results in a higher risk of age-related diseases, diminished ability to respond to new infections and reduced response to vaccines. The causes of this immune dysfunction are cellular senescence, which occurs in both lymphoid and non-lymphoid tissue, and chronic, low-grade inflammation known as 'inflammageing'. In this Review article, we highlight how the processes of inflammation and senescence drive each other, leading to loss of immune function. To break this...
Author Correction: Lithocholic acid phenocopies anti-ageing effects of calorie restriction
No abstract
Whole-body networks: a holistic approach for studying aging
Aging is a multi-organ disease, yet the traditional approach has been to study each organ in isolation. Such organ-specific studies have provided invaluable information regarding its pathomechanisms. However, an overall picture of the whole-body network (WBN) during aging is still incomplete. In this study, we analyzed the functional magnetic resonance imaging blood-oxygen level-dependent, respiratory rate and heart rate time series of a young and an elderly group during eyes-open resting-state....
Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis
The ε4 variant of human apolipoprotein E (APOE4) is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of APOE4 has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human APOE4 in Caenorhabditis elegans. The protective...
Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact...
Activated SKN-1 alters the aging trajectories of long-lived C. elegans mutants
In the presence of stressful environments, the SKN-1 cytoprotective transcription factor is activated to induce the expression of gene targets that can restore homeostasis. However, chronic activation of SKN-1 results in diminished health and a reduction of lifespan. Here we demonstrate the necessity of modulating SKN-1 activity to maintain the longevity-promoting effects associated with genetic mutations that impair daf-2/insulin receptor signaling, the eat-2 model of dietary restriction, and...
Physical Exercise Decreases Complement-Mediated Synaptic Loss and Protects Against Cognitive Impairment by Inhibiting Microglial Tmem9-ATP6V0D1 in Alzheimer's Disease
Physical exercise is known to slow synaptic neurodegeneration and cognitive aging in Alzheimer's disease (AD). The benefits of physical exercise are related to reduced amyloid beta (Aβ) deposition and increased synaptic plasticity. Yet little is known about the mechanisms that mediate these effects. Here, we show that physical exercise down-regulated the microglial Tmem9 protein, inhibited C1q activation, and decreased C1q-dependent microglial synapse engulfment, eventually ameliorating...
Persistent depressive symptom trajectory is associated with cognitive impairment: a population-based longitudinal study of aging in Taiwan
BACKGROUND: To investigate the associations between five depressive symptom trajectories and cognitive impairment in Taiwan's older population. In addition, we investigated the moderating factors influencing these associations.
Physical Exercise Decreases Complement-Mediated Synaptic Loss and Protects Against Cognitive Impairment by Inhibiting Microglial Tmem9-ATP6V0D1 in Alzheimer's Disease
Physical exercise is known to slow synaptic neurodegeneration and cognitive aging in Alzheimer's disease (AD). The benefits of physical exercise are related to reduced amyloid beta (Aβ) deposition and increased synaptic plasticity. Yet little is known about the mechanisms that mediate these effects. Here, we show that physical exercise down-regulated the microglial Tmem9 protein, inhibited C1q activation, and decreased C1q-dependent microglial synapse engulfment, eventually ameliorating...
Targeting CRM1 for Progeria Syndrome Therapy
Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disease caused by progerin, a mutant variant of lamin A. Progerin anchors aberrantly to the nuclear envelope disrupting a plethora of cellular processes, which in turn elicits senescence. We previously showed that the chromosomal region maintenance 1 (CRM1)-driven nuclear export pathway is abnormally enhanced in patient-derived fibroblasts, due to overexpression of CRM1. Interestingly, pharmacological inhibition of CRM1 using...