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Age-related remodeling of the sialoglycans dampens murine CD8<sup>+</sup> T cell function

2 months 3 weeks ago
Glycans regulate cellular function, yet how aging affects the glycocalyx remains unclear. Here, we investigate changes in immune cell glycocalyx with age and find that α2,6-linked sialic acid, a glycan epitope associated with inhibitory signaling, is down-regulated in T cells from old animals. This reduction is tightly correlated with age-associated accumulation of effector T cells, which have little to no α2,6-linked sialic acid. To understand how α2,6-linked sialic acid affects T cell...
Hanlin Zhang

Coordinated control of genome-nuclear lamina interactions by topoisomerase 2B and lamin B receptor

2 months 3 weeks ago
Lamina-associated domains (LADs) are megabase-sized genomic regions anchored to the nuclear lamina (NL). Factors controlling the interactions of the genome with the NL have largely remained elusive. Here, we identified DNA topoisomerase 2 beta (TOP2B) as a regulator of these interactions. TOP2B binds predominantly to inter-LAD (iLAD) chromatin and its depletion results in a partial loss of genomic partitioning between LADs and iLADs, suggesting that this enzyme might protect specific iLADs from...
Tom van Schaik

Enhancing Late-Life Survival and Mobility via Mitohormesis by Reducing Mitochondrial Calcium Levels

2 months 3 weeks ago
Mitochondrial calcium (Ca^(2+)) homeostasis plays a critical role in aging and cellular fitness. In the search for novel antiaging approaches, we explored how genetic and pharmacological inhibition of mitochondrial Ca^(2+) uptake influences the lifespan and health of Caenorhabditis elegans. Using live-cell imaging, we demonstrate that RNA interference-mediated knockdown of mcu-1, the nematode ortholog of the mitochondrial Ca^(2+) uniporter (MCU), reduces mitochondrial Ca^(2+) levels, thereby...
Doruntina Bresilla

New landscape of the diagnosis of Alzheimer's disease

2 months 3 weeks ago
Alzheimer's disease involves a drastic departure from the cognitive, functional, and behavioural trajectory of normal ageing, and is both a dreaded and highly prevalent cause of disability to individuals, and a leading source of health and social care expenditure for society. Before the advent of biomarkers, post-mortem examination was the only method available to establish a definitive diagnosis. In this first paper of the Series, we review state-of-the-art diagnostic practices and the typical...
Giovanni B Frisoni

Treatment for Alzheimer's disease

2 months 3 weeks ago
Over the last three decades, the evidence on how to best treat the cognitive and non-cognitive symptoms of patients with Alzheimer's disease has increased. Although these pharmacological and non-pharmacological strategies have significantly improved health outcomes for patients with Alzheimer's disease, many lack stringent evidence of efficacy. In this second paper of the Series, we provide practical and realistic advice on how to prioritise pharmacological and non-pharmacological strategies to...
Nick C Fox

Alzheimer's disease outlook: controversies and future directions

2 months 3 weeks ago
For the first time, reductions in cerebral β-amyloid pathology load and rate of cognitive and functional decline have been achieved in Alzheimer's disease, through pharmacological intervention in randomised controlled trials. However, the results from phase 3 randomised controlled trials of anti-β amyloid monoclonal antibodies are interpreted in different ways, with some experts supporting a clinically meaningful disease-modifying effect, and others judging insufficient benefit-to-risk ratio and...
Giovanni B Frisoni

Neuroanatomical correlates of auditory and visual statistical learning: Cortical and subcortical volume predictors

2 months 3 weeks ago
Statistical Learning (SL) is the ability to implicitly extract and learn statistical regularities from the environment. SL processes are ubiquitous across the lifespan through their proven role in language acquisition and adaptive behaviors. While recent neuroimaging research has identified networks of active brain regions during SL processes, less is known about whether structural differences in these regions may contribute to SL abilities. Here, we explore the extent to which visual SL (VSL)...
Praveen Prem

Assessing cerebral microvascular volumetric with high-resolution 4D cerebral blood volume MRI at 7 T

2 months 3 weeks ago
Arterial pulsation is crucial for promoting neurofluid circulation. Most previous studies quantified pulsatility via blood velocity-based indices in large arteries. Here we propose an innovative method to quantify the microvascular volumetric pulsatility index (mvPI) across cortical layers and white matter (WM) using high-resolution four-dimensional (4D) vascular space occupancy (VASO) and arterial spin labeling (ASL) magnetic resonance imaging (MRI) at 7 T with simultaneous pulse recording. We...
Fanhua Guo

Aging-related decline in the liver and brain is accelerated by refined diet consumption

2 months 3 weeks ago
Studies suggest that diets rich in highly/ultra-processed foods may contribute to the development of diseases. In rodents, the intake of refined (purified) diets has also been associated with the development of various metabolic diseases. Here, performing two experiments, we assess the impact of a refined diet with and without fiber enrichment on aging related health decline in mice. Experiment 1: Male C57BL/6J mice were fed standard chow or refined diet until the age of 86 weeks. Experiment 2:...
Franziska Kromm