Co-isolation of human donor eye cells and development of oncogene-mutated melanocytes to study uveal melanoma.

Background: Uveal melanoma (UM) is the most common intraocular tumor in adults, arises either de novo from normal choroidal melanocytes (NCMs) or from pre-existing nevi that stem from NCMs and are thought to harbor UM-initiating mutations, most commonly in GNAQ or GNA11. However, there are no commercially available NCM cell lines, nor is there a detailed protocol for developing an oncogene-mutated CM line (MutCM) to study UM development. This study aimed to establish and characterize premalignant CM models from human donor eyes to recapitulate the cell populations at the origin of UM.

Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease.

Background: Crohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesicles (EVs), adipose tissue-derived stem cells (ADSCs) can regulate their adjacent cells.

Chronic social stress induces p16-mediated senescent cell accumulation in mice.

Life stress can shorten lifespan and increase risk for aging-related diseases, but the biology underlying this phenomenon remains unclear. Here we assessed the effect of chronic stress on cellular senescence-a hallmark of aging. Exposure to restraint stress, a psychological non-social stress model, increased p21 exclusively in the brains of male, but not female mice, and in a p16-independent manner.

Stress tests and biomarkers of resilience: Proceedings of the second state of resilience science conference.

The "Stress Tests and Biomarkers of Resilience" conference, hosted by the American Geriatrics Society and the National Institute on Aging, marks the second in a series aimed at advancing the field of resilience science. Held on March 4-5, 2024, in Bethesda, Maryland, this conference built upon the foundational work from the first conference, which focused on defining resilience across various domains-physical, cognitive, and psychosocial. This year's gathering centered around three factors: the biology that underlies resilient outcomes; the social, environmental, genetic, and psychosocial factors that impact that resilience biology; and the biomarker testing and imaging that predicts resilient outcomes for older adults.

Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers.

There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer.

TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH.

Background And Aims: For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear.

Approach And Result: Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner.

Animal Models Relevant for Geroscience: Current Trends and Future Perspectives in Biomarkers, and Measures of Biological Aging.

For centuries, aging was considered inevitable and immutable. Geroscience provides the conceptual framework to shift this focus toward a new view that regards aging as an active biological process, and the biological age of an individual as a modifiable entity. Significant steps forward have been made toward the identification of biomarkers for and measures of biological age, yet knowledge gaps in geroscience are still numerous.

The mouse Social Frailty Index (mSFI): a novel behavioral assessment for impaired social functioning in aging mice.

Various approaches exist to quantify the aging process and estimate biological age on an individual level. Frailty indices based on an age-related accumulation of physical deficits have been developed for human use and translated into mouse models. However, declines observed in aging are not limited to physical functioning but also involve social capabilities.

The fortunes and misfortunes of social life across the life course: A new era of research from field, laboratory and comparative studies.

Social gradients in health and aging have been reported in studies across many human populations, and - as the papers included in this special collection highlight - also occur across species. This paper serves as a general introduction to the special collection of Neuroscience and Biobehavioral Reviews entitled "Social dimensions of health and aging: population studies, preclinical research, and comparative research using animal models". Authors of the fourteen reviews are primarily members of a National Institute of Aging-supported High Priority Research Network on "Animal Models for the Social Dimensions of Health and Aging".

Retention of stress susceptibility in the mdx mouse model of Duchenne muscular dystrophy after PGC-1α overexpression or ablation of IDO1 or CD38.

Duchenne muscular dystrophy (DMD) is a lethal degenerative muscle wasting disease caused by the loss of the structural protein dystrophin with secondary pathological manifestations including metabolic dysfunction, mood and behavioral disorders. In the mildly affected mdx mouse model of DMD, brief scruff stress causes inactivity, while more severe subordination stress results in lethality. Here, we investigated the kynurenine pathway of tryptophan degradation and the nicotinamide adenine dinucleotide (NAD+) metabolic pathway in mdx mice and their involvement as possible mediators of mdx stress-related pathology.

Functional profiling of the G protein-coupled receptor C3aR1 reveals ligand-mediated biased agonism.

G protein-coupled receptors (GPCRs) are leading druggable targets for several medicines, but many GPCRs are still untapped for their therapeutic potential due to poor understanding of specific signaling properties. The complement C3a receptor 1 (C3aR1) has been extensively studied for its physiological role in C3a-mediated anaphylaxis/inflammation, and in TLQP-21-mediated lipolysis, but direct evidence for the functional relevance of the C3a and TLQP-21 ligands and signal transduction mechanisms are still limited. In addition, C3aR1 G protein coupling specificity is still unclear, and whether endogenous ligands, or drug-like compounds, show ligand-mediated biased agonism is unknown.

Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH.

For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Here we report that VSG ameliorates MASH progression in a weight loss-independent manner.

Effect of beta-blocker therapy on weight loss outcomes after sleeve gastrectomy & Roux-en-Y gastric bypass.

Background: Patients taking beta-blockers (BBs) commonly experience weight gain. There is limited research exploring how BBs impact weight loss after bariatric surgery.

Objectives: We examined how BBs impact 12-month weight loss in patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB).

Chronic Social and Psychological Stress Impact Select Neuropathologies in the PS19 Mouse Model of Tauopathy.

Objective: Despite advances toward understanding the etiology of Alzheimer's disease (AD), it remains unclear which aspects of this disease are affected by environmental factors. Chronic life stress increases the risk of aging-related diseases including AD. The impact of stress on tauopathies remains understudied.

The impact of life stress on hallmarks of aging and accelerated senescence: Connections in sickness and in health.

Chronic stress is a risk factor for numerous aging-related diseases and has been shown to shorten lifespan in humans and other social mammals. Yet how life stress causes such a vast range of diseases is still largely unclear. In recent years, the impact of stress on health and aging has been increasingly associated with the dysregulation of the so-called hallmarks of aging.

Tumour extracellular vesicles induce neutrophil extracellular traps to promote lymph node metastasis.

Lymph nodes (LNs) are frequently the first sites of metastasis. Currently, the only prognostic LN assessment is determining metastatic status. However, there is evidence suggesting that LN metastasis is facilitated by the formation of a pre-metastatic niche induced by tumour derived extracellular vehicles (EVs).

Contextual modifiers of healthspan, lifespan, and epigenome in mice under chronic social stress.

Sustained life stress and low socioeconomic status are among the major causes of aging-related diseases and decreased life expectancy. Experimental rodent models can help to identify the underlying mechanisms, yet very few studies address the long-term consequences of social stress on aging. We conducted a randomized study involving more than 300 male mice of commonly used laboratory strains (C57BL/6J, CD1, and Sv129Ev) chosen for the spontaneous aggression gradient and stress-vulnerability.

Targeted and selective knockout of the TLQP-21 neuropeptide unmasks its unique role in energy homeostasis.

Pro-peptide precursors are processed into biologically active peptide hormones or neurotransmitters, each playing an essential role in physiology and disease. Genetic loss of function of a pro-peptide precursor results in the simultaneous ablation of all biologically-active peptides within that precursor, often leading to a composite phenotype that can be difficult to align with the loss of specific peptide components. Due to this biological constraint and technical limitations, mice carrying the selective ablation of individual peptides encoded by pro-peptide precursor genes, while leaving the other peptides unaffected, have remained largely unaddressed.

Chronic low-level JUUL aerosol exposure causes pulmonary immunologic, transcriptomic, and proteomic changes.

E-cigarettes currently divide public opinion, with some considering them a useful tool for smoking cessation and while others are concerned with potentially adverse health consequences. However, it may take decades to fully understand the effects of e-cigarette use in humans given their relative newness on the market. This highlights the need for comprehensive preclinical studies investigating the effects of e-cigarette exposure on health outcomes.

The multiple roles of life stress in metabolic disorders.

The activation of stress-related neuroendocrine systems helps to maintain homeostasis, but excessive stress can damage body functions. We review current evidence from basic sciences and epidemiology linking stress to the development and progression of metabolic disorders throughout life. Findings from rodents demonstrate that stress can affect features of metabolic dysfunction, such as insulin resistance, glucose and lipid homeostasis, as well as ageing processes such as cellular senescence and telomere length shortening.

Juvenile exposure to doxorubicin alters the cardiovascular response to adult-onset psychosocial stress in mice.

Childhood cancer survivors have a high risk for premature cardiovascular diseases, mainly due to cardiotoxic cancer treatments such as doxorubicin (DOX). Psychosocial stress is a significant cardiovascular risk factor and an enormous burden in childhood cancer survivors. Although observational studies suggest that psychosocial stress is associated with cardiovascular complications in cancer survivors, there is no translationally relevant animal model to study this interaction.