1,383 results match your criteria: "The Buck Institute for Research on Aging; glithgow@buckinstitute.org.[Affiliation]"

Guidelines for minimal information on cellular senescence experimentation in vivo.

Cell

August 2024

European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), Groningen, the Netherlands. Electronic address:

Article Synopsis
  • * New research tools are helping scientists study senescence more effectively, but identifying senescent cells remains challenging because of a lack of clear markers.
  • * The "minimum information for cellular senescence experimentation in vivo" (MICSE) guidelines offer a comprehensive resource on senescence markers in different organisms and types of tissues to enhance the study of senescent cells.
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Synthetic data generation in omics mimics real-world biological data, providing alternatives for training and evaluation of genomic analysis tools, controlling differential expression, and exploring data architecture. We previously developed Precious1GPT, a multimodal transformer trained on transcriptomic and methylation data, along with metadata, for predicting biological age and identifying dual-purpose therapeutic targets potentially implicated in aging and age-associated diseases. In this study, we introduce Precious2GPT, a multimodal architecture that integrates Conditional Diffusion (CDiffusion) and decoder-only Multi-omics Pretrained Transformer (MoPT) models trained on gene expression and DNA methylation data.

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Design and validation of the ADNI MR protocol.

Alzheimers Dement

September 2024

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

Phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) magnetic resonance imaging (MRI) protocols aim to maintain longitudinal consistency across two decades of data acquisition, while adopting new technologies. Here we describe and justify the study's design and targeted biomarkers. The ADNI4 MRI protocol includes nine MRI sequences.

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Background: Adults with Parkinson disease (PD) are hospitalized at higher rates than age-matched controls, and these hospitalizations are associated with significant morbidity. However, little is known about the consequences of critical illness requiring intensive care unit (ICU)-level care in patients with PD. The aim of this study was to define the characteristics and outcomes of adults with PD admitted to the ICU.

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Development of an epigenetic clock resistant to changes in immune cell composition.

Commun Biol

August 2024

Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, 94945, CA, USA.

Epigenetic clocks are age predictors that use machine-learning models trained on DNA CpG methylation values to predict chronological or biological age. Increases in predicted epigenetic age relative to chronological age (epigenetic age acceleration) are connected to aging-associated pathologies, and changes in epigenetic age are linked to canonical aging hallmarks. However, epigenetic clocks rely on training data from bulk tissues whose cellular composition changes with age.

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Sirt5 regulates chondrocyte metabolism and osteoarthritis development through protein lysine malonylation.

bioRxiv

August 2024

Department of Biomedical Sciences, Heritage College of Osteopathic Medicine (HCOM), Ohio University, Athens, OH, 45701, USA.

Objectives: Chondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post-translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development.

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Article Synopsis
  • - This study investigates the molecular differences between breast cancer survivors and healthy controls using advanced techniques like genomics and metabolomics, involving a total of 100 participants.
  • - Findings revealed that breast cancer survivors had higher polygenic risk scores and notable differences in metabolites, particularly lower Omega-3 Index levels, compared to healthy individuals.
  • - The research contributes significant data that can help identify patterns in breast cancer survivorship, with the potential to inform new treatment strategies and improve the quality of life for those affected.
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Applying the area fraction fractionator (AFF) probe for total volume estimations of somatic, dendritic and axonal domains of the nigrostriatal dopaminergic system in a murine model.

J Neurosci Methods

October 2024

Laboratorio de Neuroanatomía, Departamento de Anatomía, and Centro Interdisciplinario de Neurociencia, NeuroUC, Escuela de Medicina, Pontificia Universidad Católica de Chile, Chile; Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Chile. Electronic address:

Background: The Cavalieri estimator is used for volume measurement of brain and brain regions. Derived from this estimator is the Area Fraction Fractionator (AFF), used for efficient area and number estimations of small 2D elements, such as axons in cross-sectioned nerves. However, to our knowledge, the AFF has not been combined with serial sectioning analysis to measure the volume of small-size nervous structures.

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Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function.

Cell Rep Med

July 2024

Institute for Systems Biology, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; eScience Institute, University of Washington, Seattle, WA 98195, USA. Electronic address:

Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context.

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Extraordinary model systems for regeneration.

Development

October 2024

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Regeneration is the remarkable phenomenon through which an organism can regrow lost or damaged parts with fully functional replacements, including complex anatomical structures, such as limbs. In 2019, Development launched its 'Model systems for regeneration' collection, a series of articles introducing some of the most popular model organisms for studying regeneration in vivo. To expand this topic further, this Perspective conveys the voices of five expert biologists from the field of regenerative biology, each of whom showcases some less well-known, but equally extraordinary, species for studying regeneration.

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The infrapatellar fat pad in inflammaging, knee joint health, and osteoarthritis.

NPJ Aging

July 2024

Center for AI and Data Science of Aging, Buck Institute for Research on Aging, Novato, CA, 94945, USA.

Osteoarthritis (OA) is the most common form of arthritis and accounts for nearly $140 billion in annual healthcare expenditures only in the United States. Obesity, aging, and joint injury are major risk factors for OA development and progression, but the mechanisms contributing to pathology remain unclear. Emerging evidence suggests that cellular dysregulation and inflammation in joint tissues, including intra-articular adipose tissue depots, may contribute to disease severity.

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Article Synopsis
  • In frontotemporal lobar degeneration (FTLD), abnormal protein buildup in the brain correlates with declines in social-emotional and language skills, primarily involving TDP-43 or tau proteins.
  • The study investigates how degeneration patterns in FTLD relate to gene expression of recently evolved genetic regions, using neuroimaging and transcriptomic data to examine targeted brain areas.
  • Results indicate that FTLD subtypes uniquely or overlappingly affect brain regions tied to genes evolved in humans, with a notable relationship between TDP-43 function impairment and cryptic splicing in affected genes.
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Microbially derived short-chain fatty acids (SCFAs) in the human gut are tightly coupled to host metabolism, immune regulation and integrity of the intestinal epithelium. However, the production of SCFAs can vary widely between individuals consuming the same diet, with lower levels often associated with disease. A systems-scale mechanistic understanding of this heterogeneity is lacking.

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Increasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decrease proliferation.

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Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P.

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In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging.

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Article Synopsis
  • Cellular senescence is linked to aging and diseases, but measuring senescent cells is difficult due to a lack of specific markers and methods.
  • The Fully-Automated Senescence Test (FAST) is introduced as an efficient, image-based technique to evaluate senescence in cultured cells by assessing key markers like SA-β-Gal activity, proliferation arrest, and cell morphology.
  • FAST offers standardized, automated imaging and data analysis, minimizing false positives, and enables large-scale experiments in aging research by accurately quantifying senescence across various cell types.
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Telomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models.

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Article Synopsis
  • Spaceflight triggers an immune response in astronauts, which was analyzed during the SpaceX Inspiration4 mission using various data types, including single-cell and biochemical analysis.
  • Researchers identified a "spaceflight signature" in gene expression linked to processes like oxidative phosphorylation, immune function, and inflammation, found across multiple datasets.
  • Key findings include up-regulation of specific immune markers in T cells, long-term suppression of certain MHC class I genes, and changes in infection-related immune pathways due to shifts in the microbiome.
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Microgravity is associated with immunological dysfunction, though the mechanisms are poorly understood. Here, using single-cell analysis of human peripheral blood mononuclear cells (PBMCs) exposed to short term (25 hours) simulated microgravity, we characterize altered genes and pathways at basal and stimulated states with a Toll-like Receptor-7/8 agonist. We validate single-cell analysis by RNA sequencing and super-resolution microscopy, and against data from the Inspiration-4 (I4) mission, JAXA (Cell-Free Epigenome) mission, Twins study, and spleens from mice on the International Space Station.

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The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Nature

August 2024

Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study, JAXA CFE study, SpaceX Inspiration4 crew, Axiom and Polaris.

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A second space age spanning omics, platforms and medicine across orbits.

Nature

August 2024

Blue Marble Space Institute of Science, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA, USA.

The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a 'second space age'. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews.

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The capacity to deal with stress declines during the aging process, and preservation of cellular stress responses is critical to healthy aging. The unfolded protein response of the endoplasmic reticulum (UPR) is one such conserved mechanism, which is critical for the maintenance of several major functions of the ER during stress, including protein folding and lipid metabolism. Hyperactivation of the UPR by overexpression of the major transcription factor, , solely in neurons drives lifespan extension as neurons send a neurotransmitter-based signal to other tissue to activate UPR in a non-autonomous fashion.

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