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The balance between IFN-γ and ERK/MAPK signaling activities ensures lifelong maintenance of intestinal stem cells

3 months 3 weeks ago
While the intestinal epithelium has the highest cellular turnover rates in the mammalian body, it is also considered one of the tissues most resilient to aging-related disorders. Here, we reveal an innate protective mechanism that safeguards intestinal stem cells (ISCs) from environmental conditions in the aged intestine. Using in vivo phenotypic analysis, transcriptomics, and in vitro intestinal organoid studies, we show that age-dependent activation of interferon-γ (IFN-γ) signaling and...
May Nakajima-Koyama

Healthy Aging Metabolomic and Proteomic Signatures Across Multiple Physiological Compartments

3 months 3 weeks ago
The study of biomarkers in biofluids and tissues expanded our understanding of the biological processes that drive physiological and functional manifestations of aging. However, most of these studies were limited to examining one biological compartment, an approach that fails to recognize that aging pervasively affects the whole body. The simultaneous modeling of hundreds of metabolites and proteins across multiple compartments may provide a more detailed picture of healthy aging and point to...
R Moaddel

Inhibition of 15-PGDH by SW033291 ameliorates age-related heart failure in mice

3 months 3 weeks ago
Chronic loss of cardiomyocyte integrity underlies human heart failure associated with aging that often involves progression of acute myocardial infarction and the maladaptive response of cardiomyopathy. SW033291, an inhibitor of 15-prostaglandin dehydrogenase (15-PGDH), has been shown to mitigate fibrosis of mice heart. Whether it has cardioprotective effect remain unknown. Young and aged C57BL/6 J mice were treated with either the vehicle or SW033291 for four weeks. The expression of the target...
Li Zhang

Bridging gap in the treatment of Alzheimer's disease via postbiotics: Current practices and future prospects

3 months 3 weeks ago
Aging is an extremely significant risk associated with neurodegeneration. The most prevalent neurodegenerative disorders (NDs), such as Alzheimer's disease (AD) are distinguished by the prevalence of proteinopathy, aberrant glial cell activation, oxidative stress, neuroinflammation, defective autophagy, cellular senescence, mitochondrial dysfunction, epigenetic changes, neurogenesis suppression, increased blood-brain barrier permeability, and intestinal dysbiosis that is excessive for the...
Bushra Bashir

Model-constrained deep learning for online fault diagnosis in Li-ion batteries over stochastic conditions

3 months 3 weeks ago
For the intricate and infrequent safety issues of batteries, online safety fault diagnosis over stochastic working conditions is indispensable. In this work, we employ deep learning methods to develop an online fault diagnosis network for lithium-ion batteries operating under unpredictable conditions. The network integrates battery model constraints and employs a framework designed to manage the evolution of stochastic systems, thereby enabling fault real-time determination. We evaluate the...
Rui Cao

Single-cell analysis identifies Ifi27l2a as a gene regulator of microglial inflammation in the context of aging and stroke in mice

3 months 3 weeks ago
Inflammation is a significant driver of ischemic stroke pathology in the brain. To identify potential regulators of inflammation, we performed single-cell RNA sequencing (scRNA-seq) of young and aged mouse brains following stroke and found that interferon alpha-inducible protein 27 like 2 A (Ifi27l2a) was significantly up-regulated, particularly in microglia of aged brain. Ifi27l2a is induced by interferons for viral host defense and has been linked with pro-inflammatory cellular mechanisms....
Gab Seok Kim

Adaptation of LASA sedentary behaviour questionnaire into Turkish and examination of its psychometric properties in elderly individuals

3 months 3 weeks ago
CONCLUSION-DISCUSSION: The LASA-SBQ was translated into Turkish and culturally adapted. The psychometric properties of the questionnaire were examined and validity and reliability analyses were performed. The Turkish version of the LASA-SBQ is a valid and reliable scale and is suitable for use in scientific research.
Müseddin Muratoglu

The vulnerability of hip fracture patients with cognitive impairment: an analysis of health conditions, hospital care, and outcomes

3 months 3 weeks ago
CONCLUSIONS: Hip fracture patients with cognitive impairment, particularly severe impairment, arrive at the ED in a considerably poorer state of health and are at a higher risk of adverse outcomes, including complications and mortality. Timely identification of this at-risk group upon arrival appears to be essential to providing adequate care. This study highlights the need for interventions and research aimed at improving prevention, emergency care and outcomes for this vulnerable group,...
Dorothea Birkner

Interpretable AI for inference of causal molecular relationships from omics data

3 months 3 weeks ago
The discovery of molecular relationships from high-dimensional data is a major open problem in bioinformatics. Machine learning and feature attribution models have shown great promise in this context but lack causal interpretation. Here, we show that a popular feature attribution model, under certain assumptions, estimates an average of a causal quantity reflecting the direct influence of one variable on another. We leverage this insight to propose a precise definition of a gene regulatory...
Payam Dibaeinia

Dynamic changes in neuronal and glial GAL4 driver expression during Drosophila aging

3 months 3 weeks ago
Understanding how diverse cell types come together to form a functioning brain relies on the ability to specifically target these cells. This is often done using genetic tools such as the GAL4/UAS system in Drosophila melanogaster. Surprisingly, despite its extensive usage during studies of the aging brain, detailed spatiotemporal characterization of GAL4 driver lines in adult flies has been lacking. Here, we show that 3 commonly used neuronal drivers (elav[C155]-GAL4, nSyb[R57C10]-GAL4, and...
Caroline Delandre

Test of Rapamycin in Aging Dogs (TRIAD): study design and rationale for a prospective, parallel-group, double-masked, randomized, placebo-controlled, multicenter trial of rapamycin in healthy middle-aged dogs from the Dog Aging Project

3 months 3 weeks ago
Companion dogs are a powerful model for aging research given their morphologic and genetic variability, risk for age-related disease, and habitation of the human environment. In addition, the shorter life expectancy of dogs compared to human beings provides a unique opportunity for an accelerated timeline to test interventions that might extend healthy lifespan. The Test of Rapamycin In Aging Dogs (TRIAD) randomized clinical trial is a parallel-group, double-masked, randomized,...
Amanda E Coleman

fmo-4 promotes longevity and stress resistance via ER to mitochondria calcium regulation in C. elegans

3 months 3 weeks ago
Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, and healthspan by rewiring endogenous metabolism. However, there are five C. elegans FMOs and five mammalian FMOs, and it is not known whether promoting longevity and health benefits is a conserved role of this gene family. Here, we report that...
Angela M Tuckowski