651 results match your criteria: "Barshop Institute for Longevity and Aging Studies[Affiliation]"

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

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Circadian disruption is pervasive in modern society and associated with increased risk of disease. Chronic jet lag paradigms are popular experimental tools aiming to emulate human circadian disruption experienced during rotating and night shift work. Chronic jet lag induces metabolic phenotypes tied to liver and systemic functions, yet lack of a clear definition for how rhythmic physiology is impaired under these conditions hinders the ability to identify the underlying molecular mechanisms.

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Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection against diet-induced obesity. In this study, we used temporal metabolomics on HeLa cells to show that MTCH2 deletion results in a high ATP demand, an oxidized cellular environment, and elevated utilization of lipids, amino acids, and carbohydrates, accompanied by a decrease in several metabolites.

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Objective: The objective of this study was to evaluate the effect of glucagon-like peptide-1 receptor agonist (GLP1Ra)-based therapies on change in dual-energy x-ray absorptiometry (DXA)-acquired lean mass (LM) or bone mineral density (BMD).

Methods: PubMed and Web of Science were searched from database inception through January 29, 2024, for randomized, placebo-controlled trials reporting on change in DXA-acquired LM or BMD measures associated with 12+ weeks of GLP1Ra-based treatment. Of 2618 articles, 9 trials met prespecified search criteria, with 7 reporting on change in total body LM and 2 reporting on change in BMD.

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Mexican Health and Aging Study Biomarker and Genetic Data Profile.

J Gerontol A Biol Sci Med Sci

December 2024

Department of Population Health Sciences, UTHealth San Antonio, Texas, USA.

The Mexican Health and Aging Study (MHAS) is one of the largest ongoing longitudinal studies of aging in Latin America, with six waves over 20 years. MHAS includes sociodemographic, economic, and health data from a nationally representative sample of adults 50 years and older in urban and rural Mexico. MHAS is designed to study the impact of diseases on adults' health, function, and mortality.

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Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

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Lipids, which constitute the highest portion (over 50%) of brain dry mass, are crucial for brain integrity, energy homeostasis, and signaling regulation. Emerging evidence revealed that lipid profile alterations and abnormal lipid metabolism occur during normal aging and in different forms of neurodegenerative diseases. Moreover, increasing genome-wide association studies have validated new targets on lipid-associated pathways involved in disease development.

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CELF2 promotes tau exon 10 inclusion via hinge domain-mediated nuclear condensation.

bioRxiv

November 2024

Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

Alternative splicing is a fundamental process that contributes to the functional diversity and complexity of proteins. The regulation of each alternative splicing event involves the coordinated action of multiple RNA-binding proteins, creating a diverse array of alternatively spliced products. Dysregulation of alternative splicing is associated with various diseases, including neurodegeneration.

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Identification of lipid senolytics targeting senescent cells through ferroptosis induction.

bioRxiv

October 2024

Institute on the Biology of Aging and Metabolism and the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.

Cellular senescence is a key driver of the aging process and contributes to tissue dysfunction and age-related pathologies. Senolytics have emerged as a promising therapeutic intervention to extend healthspan and treat age-related diseases. Through a senescent cell-based phenotypic drug screen, we identified a class of conjugated polyunsaturated fatty acids, specifically α-eleostearic acid and its methyl ester derivative, as novel senolytics that effectively killed a broad range of senescent cells, reduced tissue senescence, and extended healthspan in mice.

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Mouse models used to test the role of reactive oxygen species in aging and age-related chronic diseases.

Free Radic Biol Med

November 2024

Department of Biochemistry & Molecular Biology, University of Oklahoma Health Sciences, Oklahoma City, OK, USA; VA Oklahoma Health Care System, Oklahoma City, OK, USA. Electronic address:

With the development of the technology to generate transgenic and knockout mice in the 1990s, investigators had a powerful tool to directly test the impact of altering a specific gene on a biological process or disease. Over the past three decades, investigators have used transgenic and knockout mouse models, which have altered expression of antioxidant genes, to test the role of oxidative stress/damage in aging and age-related diseases. In this comprehensive review, we describe the studies using transgenic and knockout mouse models to test the role of oxidative stress/damage in aging (longevity) and three age-related diseases, e.

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Article Synopsis
  • Mitochondria are essential for brain health, influencing energy production, inflammation, and hormone synthesis, and their dysfunction is connected to neurodegenerative diseases like Alzheimer's and Parkinson's.
  • Research on aging baboons revealed a decline in the activity of mitochondrial electron transport chain (ETC) complexes in the prefrontal cortex, mainly tied to alterations in individual complex functions rather than overall mitochondrial numbers.
  • Female baboons maintained mitochondrial function better with age compared to males, who exhibited significant ETC activity loss and had correlations between walking speed and respiration linked to higher ETC complexes, pointing to possible reasons behind sex differences in brain resilience as they age.
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APOE is a major genetic factor in late-onset Alzheimer's disease (LOAD), with APOE4 increasing risk, APOE3 acting as neutral, and APOE2 offering protection. APOE also plays key role in lipid metabolism, affecting both peripheral and central systems, particularly in lipoprotein metabolism in triglyceride and cholesterol regulation. APOE2 is linked to Hyperlipoproteinemia type III (HLP), characterized by mixed hypercholesterolemia and hypertriglyceridemia due to impaired binding to Low-Density Lipoproteins receptors.

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The microtubule regulator EFA-6 forms cortical foci dependent on its intrinsically disordered region and interactions with tubulins.

Cell Rep

October 2024

Department of Neurobiology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, San Diego, CA 92093, USA. Electronic address:

The EFA6 protein family, originally identified as Sec7 guanine nucleotide exchange factors, has also been found to regulate cortical microtubule (MT) dynamics. Here, we find that in the mature C. elegans epidermal epithelium, EFA-6 forms punctate foci in specific regions of the apical cortex, dependent on its intrinsically disordered region (IDR).

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Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism.

Commun Biol

September 2024

Cellular Neuroscience, Neurodegeneration, Repair, Departments of Neurology and of Neuroscience, Yale University School of Medicine, New Haven, CT, 06536, USA.

Article Synopsis
  • - TMEM106B is a protein linked to various neurological disorders such as frontotemporal dementia and Alzheimer's, and it's being studied for its potential involvement in COVID-19.
  • - Research revealed that mice lacking TMEM106B showed reduced levels of key myelin lipids, specifically galactosylceramide and sulfatide, indicating a role in lipid metabolism.
  • - The study found that TMEM106B interacts with the enzyme galactosylceramidase, which was more active in the absence of TMEM106B, suggesting it plays a crucial role in regulating myelin lipids relevant to related diseases.
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Background: The incidence and mortality rates of hepatocellular carcinoma among Hispanic individuals in the United States are much higher than in non-Hispanic White people. We conducted multi-omics analyses to elucidate molecular alterations in hepatocellular carcinoma among Hispanic patients.

Methods: Paired tumor and adjacent nontumor samples were collected from 31 Hispanic hepatocellular carcinomas in South Texas for genomic, transcriptomic, proteomic, and metabolomic profiling.

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The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.

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The RAD51 S181P mutation shortens lifespan of female mice.

Mutat Res

November 2024

Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health San Antonio, San Antonio, Texas, USA; Mays Cancer Center, University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, Texas, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, Texas, USA. Electronic address:

RAD51 is critical to the homologous recombination (HR) pathway that repairs DNA double strand breaks (DSBs) and protects replication forks (RFs). Previously, we showed that the S181P (SP) mutation in RAD51 causes defective RF maintenance but is proficient for DSB repair. Here we report that SP/SP female mice exhibit a shortened lifespan compared to +/+ females but not males.

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Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function.

Cell Metab

August 2024

UConn Center on Aging, UConn Health, Farmington, CT 06030, USA; Department of Genetics and Genome Sciences, UConn Health, Farmington, CT 06030, USA. Electronic address:

A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21 (p21) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21 cells improves physical function at all remaining stages of life, suggesting healthspan extension.

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Ceramide-induced cleavage of GPR64 intracellular domain drives Ewing sarcoma.

Cell Rep

August 2024

Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Mays Cancer Center, The University of Texas Health Science Center, San Antonio, TX 78229, USA; Department of Biochemistry and Structural Biology, The University of Texas Health Science Center, San Antonio, TX 78229, USA. Electronic address:

Ewing sarcoma is a cancer of bone and soft tissue in children and young adults primarily driven by the EWS-FLI1 fusion oncoprotein, which has been undruggable. Here, we report that Ewing sarcoma depends on secreted sphingomyelin phosphodiesterase 1 (SMPD1), a ceramide-generating enzyme, and ceramide. We find that G-protein-coupled receptor 64 (GPR64)/adhesion G-protein-coupled receptor G2 (ADGRG2) responds to ceramide and mediates critical growth signaling in Ewing sarcoma.

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Wnt/Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression.

Proc Natl Acad Sci U S A

July 2024

Department of Biochemistry and Molecular Biology, Louisiana Cancer Research Center, Tulane University School of Medicine, New Orleans, LA 70112.

The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its role in regulating lipid homeostasis remains not fully understood. Here, we report that the activation of canonical Wnt/Wg signaling promotes lipolysis while concurrently inhibiting lipogenesis and fatty acid β-oxidation in both larval and adult adipocytes, as well as cultured S2R+ cells, in . Using RNA-sequencing and CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assays, we identified a set of Wnt target genes responsible for intracellular lipid homeostasis.

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Article Synopsis
  • - PAQR4 is an orphan receptor that plays a crucial role in adipose tissue function and overall metabolic health, with its expression linked to lipodystrophy, hyperglycaemia, and hyperinsulinaemia when present in adipocytes.
  • - The deletion of PAQR4 in adipocytes leads to better adipose remodelling and improved glucose regulation in obesity, implying that PAQR4 has a negative impact when overactive.
  • - PAQR4 affects ceramide levels by regulating the stability of ceramide synthases, and excess ceramide leads to poor adipose tissue function; thus, targeting PAQR4 could help treat metabolic disorders.
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Alterations in the rate and accuracy of messenger RNA (mRNA) translation are associated with aging and several neurodegenerative disorders, including Alzheimer's disease and related tauopathies. We previously reported that error-containing RNA that are normally cleared via nonsense-mediated mRNA decay (NMD), a key RNA surveillance mechanism, are translated in the adult brain of a Drosophila model of tauopathy. In the current study, we find that newly-synthesized peptides and translation machinery accumulate within nuclear envelope invaginations that occur as a consequence of tau pathology, and that the rate of mRNA translation is globally elevated in early stages of disease in adult brains of Drosophila models of tauopathy.

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