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The Human Cardiac "Age-OME": Age-Specific Changes in Myocardial Molecular Expression

1 month 1 week ago
Ageing is one of the most significant risk factors for heart disease; however, it is still not clear how the human heart changes with age. Taking advantage of a unique set of pre-mortem, cryopreserved, non-diseased human hearts, we performed omics analyses (transcriptomics, proteomics, metabolomics, and lipidomics), coupled with biologically informed computational modelling in younger (≤ 25 years old) and older hearts (≥ 50 years old) to describe the molecular landscape of human cardiac ageing....
Cassandra Malecki

Peri- and Postnatal High Fat Feeding Have Differential Effects on Executive Function and Associated Neurobiology in Aged Male and Female Mice

1 month 1 week ago
Almost half of pregnant women globally are currently estimated to be overweight or obese. Rates of childhood obesity are also on the rise, in part because of increased consumption of dietary saturated fats. However, the long-term effect of peri- and postnatal high fat (HF) feeding on cognitive function and neuronal expression has not yet been investigated. Male and female C57BL/6J mice born to dams fed a control (C) or high fat (HF) diet were themselves fed either the C or HF diet, generating...
Laura Contu

Chemogenetic tuning reveals optimal MAPK signaling for cell-fate programming

1 month 1 week ago
Cell states evolve through the combined activity of signaling pathways and gene networks. While transcription factors can direct cell fate, these factors rely on a receptive cell state. How signaling levels contribute to the emergence of receptive cell states remains poorly defined. Using a well-defined model of direct conversion, we examined how levels of the mitogen-activated protein kinase (MAPK)-activating oncogene HRAS^(G12V) influence direct conversion of primary fibroblasts to induced...
Brittany A Lende-Dorn

Aging-related adaptations of metabotropic glutamate receptors within the CA3 region of the rat hippocampus

1 month 1 week ago
The physiological decline associated with aging is often accompanied by a progressive deterioration in cognitive processing abilities driven by a series of cellular dysfunctions that remain poorly understood. In the hippocampus, a critical area for learning and memory, aging affects the functional expression of ionotropic and metabotropic receptors, including the metabotropic glutamate receptors (mGluRs). mGluRs play a critical role in multiple cellular functions, including modulation of ion...
Emilio J Galván

Blackcurrant anthocyanins improve visual contrast resolution for optokinetic responses in aging mice

1 month 1 week ago
Visual motion perception declines during natural aging in most animals including humans. Edible berries of blackcurrant (BC) and its extracted anthocyanins (BCAs) have beneficial effects on human eyes. However, the effect of BCAs on the perception of moving objects and other dynamic visual patterns remains unknown. In the current study, we investigated whether BCAs improve visual movement perception in aging mice. The aging mice were fed either a standard diet or a standard diet containing BC....
Yuko Sugita

AlzFormer: Video-based space-time attention model for early diagnosis of Alzheimer's disease

1 month 1 week ago
Early and accurate Alzheimer's disease (AD) diagnosis is critical for effective intervention, but it is still challenging due to neurodegeneration's slow and complex progression. Recent studies in brain imaging analysis have highlighted the crucial roles of deep learning techniques in computer-assisted interventions for diagnosing brain diseases. In this study, we propose AlzFormer, a novel deep learning framework based on a space-time attention mechanism, for multiclass classification of AD,...
Taymaz Akan

Cognitive prediction using regional connectivities and network biomarkers in Alzheimer's disease

1 month 1 week ago
Achieving a deep understanding of brain mechanisms requires multi-scale perspectives to capture the architecture of complex networks. In this study, we focused on patients with cognitive impairment and constructed individual brain networks from neuroimaging data. We introduced a Significant Edges Selection (SES) method, which effectively extracts the most informative connections while suppressing noise. Using these refined features, we computed network characteristics and applied machine...
Jinhua Sheng

Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer's Disease

1 month 1 week ago
The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). We include 452...
Toomas Erik Anijärv

Gut microbial production of imidazole propionate drives Parkinson's pathologies

1 month 1 week ago
Parkinson's disease (PD) is characterized by the selective degeneration of midbrain dopaminergic neurons and aggregation of α-synuclein. Emerging evidence implicates the gut microbiome in PD, with microbial metabolites proposed as potential pathological mediators. However, the specific microbes and metabolites involved, and whether gut-derived metabolites can reach the brain to directly induce neurodegeneration, remain unclear. Here we show that elevated levels of Streptococcus mutans (S....
Hyunji Park

A blood-based DNA damage signature in patients with Parkinson's disease is associated with disease progression

1 month 1 week ago
Aging is the main risk factor for Parkinson's disease (PD), yet our understanding of how age-related mechanisms contribute to PD pathophysiology remains limited. We conducted a longitudinal analysis of blood samples from the Parkinson's Progression Markers Initiative cohort to investigate DNA damage in PD. Patients with PD exhibited disrupted DNA repair pathways and biased suppression of longer transcripts, indicating age-related, transcription-stalling DNA damage. Notably, at the intake visit,...
Daisy Sproviero

Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging

1 month 1 week ago
Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team...
Jessica Pham

Effect of henagliflozin on aging biomarkers in patients with type 2 diabetes: A multicenter, randomized, double-blind, placebo-controlled study

1 month 1 week ago
Sodium-glucose cotransporter-2 inhibitors have been proposed as caloric restriction mimetics with potential anti-aging effects. However, clinical data on their influence on aging biomarkers are limited. In this multicenter, randomized, double-blind, placebo-controlled trial, 150 participants with type 2 diabetes are randomized (1:1) to receive oral henagliflozin (10 mg/day) or placebo for 26 weeks. Compared with placebo, henagliflozin significantly increases telomere length (primary endpoint),...
Jie Zhang