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Modulation of neuronal oscillations holds promise for the treatment of neurological disorders. Nonetheless, conventional stimulation in a continuous open-loop manner can lead to side effects and suboptimal efficiency. Closed-loop strategies such as phase-locked stimulation aim to address these shortcomings by offering a more targeted modulation. While theories have been developed to understand the neural response to stimulation, their predictions have not been thoroughly tested using...

The autophagy-lysosomal system comprises a highly dynamic and interconnected vesicular network that plays a central role in maintaining proteostasis and cellular homeostasis. In this study, we uncovered the deubiquitinating enzyme (DUB), dUsp45/USP45, as a key player in regulating autophagy and lysosomal activity in Drosophila and mammalian cells. Loss of dUsp45/USP45 results in autophagy activation and increased levels of V-ATPase to lysosomes, thus enhancing lysosomal acidification and...

CONCLUSION: A sex-based variation in the rate of aortic morphological aging is observed throughout the lifespan, with females showing more pronounced changes in aortic tortuosity. It highlights the importance of prioritizing preventive measures for females, who may benefit more due to sex-specific disparities.

Aging is a principal driver of cardiomyopathy, characterized by mitochondrial dysfunction, oxidative stress, and progressive telomere shortening in cardiomyocytes. These pathological changes impair cellular bioenergetics and regenerative capacity, accelerating cardiac deterioration. However, targeted interventions to mitigate these effects remain limited. This research investigates the therapeutic potential of CISD1 activation as a novel strategy to counteract aging-associated cardiac decline....

The present study aimed at determining the test-retest reliability of commonly used measures in a sample of middle-aged and older participants who presented with a wide range of functional abilities. Participants were middle-aged (40-55 years) and older adults (> 60 years) with- and without mobility limitations, tested both before and after a 4-week period (n = 43). Measures included maximal dynamic (1-RM) and isometric strength, surface EMG (sEMG), peak power, ultrasound-derived muscle size and...

Aging is a driving factor of various non-communicable diseases. Air pollution and greenspace also affect human health to varying degrees. However, the relationship between air pollution, green space and aging has not been clearly studied. To address this gap, we conducted a study estimating the biological age of 156,690 individuals in the UK Biobank using the PhenoAge algorithm from clinical traits. We defined the residual between biological age and actual age as Phenotypic Age Acceleration...

The disease course and outcome of COVID-19 greatly varies between individuals. To explore which biological systems may contribute to this variation, we examined how individual metabolites and three metabolic scores relate to COVID-19 outcomes in hospitalized COVID-19 patients. The metabolome of 346 patients was measured using the 1H-NMR Nightingale platform. The association of individual metabolomic features and multi-biomarker scores, i.e. MetaboHealth, MetaboAge, and Infectious Disease Score...

Age-related reductions in cerebellar integrity predict motor impairments in older adults (OA), but the contribution of cerebro-cerebellar interactions to these impairments remains unclear. Understanding these interactions could reveal underlying mechanisms associated with age-related deficits in motor control. To explore this, twenty younger adults (YA) and twenty OA, all right-handed, participated in a dual-site transcranial magnetic stimulation protocol. Cerebellar brain inhibition (CBI) was...

Lipid nanoparticles have shown success in targeting major organs such as the liver, spleen, and lungs, but crossing the blood-brain barrier (BBB) remains a major challenge. Effective brain-targeted delivery systems are essential for advancing gene therapy for neurological diseases but remain limited by low transport efficiency and poor nucleic acid stability. Here, we report a library of ionizable lipids based on the tetrahydroisoquinoline structure of protoberberine alkaloids, designed to...

Dystrophic neurites (also termed axonal spheroids) are found around amyloid deposits in Alzheimer's disease (AD), where they impair axonal electrical conduction, disrupt neural circuits and correlate with AD severity. Despite their importance, the mechanisms underlying spheroid formation remain incompletely understood. To address this, we developed a proximity labeling approach to uncover the proteome of spheroids in human postmortem and mouse brains. Additionally, we established a human induced...

Alzheimer's disease (AD) is characterized by progressive cognitive decline, severe brain atrophy and neuroinflammation. We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 2a clinical trial that tested the safety and efficacy of laromestrocel, a bone-marrow-derived, allogeneic mesenchymal stem-cell therapy, in slowing AD clinical progression, atrophy and neuroinflammation. Participants across ten centers in the United States were randomly assigned 1:1:1:1 to four...

Aging is driven by fundamental mechanisms like oxidative stress, telomere shortening and changes in DNA methylation, which together prepare the ground for age-related diseases. Botanical extracts, rich in bioactive phytoconstituents, represent a promising resource for developing therapies that target these mechanisms to promote healthy aging. This study explores the geroprotective potential of Monarda didyma L. extract. In vitro analyses revealed the extract's strong antioxidant activity,...

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. Here we describe upper respiratory tract (URT) and peripheral blood transcriptomes of 202 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 65 healthy individuals. Among healthy children and adolescents, younger age is associated with higher URT expression of innate and adaptive immune pathways. SARS-CoV-2 infection induces broad...

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Many different animal developmental and homeostatic processes rely on signalling via the highly conserved Notch pathway. Often Notch signalling has iterative roles during cell specification and differentiation, controlling not only the state of progenitor cells but also the fate and function of their progeny. Its roles continue throughout the lifespan of the organism, regulating normal tissue maintenance, as well as operating in response to damage. Consistent with such fundamental roles, the...