Genotype and Biological Age Impact Inter-Omic Associations Related to Bioenergetics.

Apolipoprotein E ( ) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. Herein, we analyzed inter-omic, context-dependent association patterns across genotypes, sex, and health axes in 2,229 community-dwelling individuals to test genotypes for variation in metabolites and metabolite-associations tied to a previously-validated metric of biological aging (BA) based on blood biomarkers.

Metabolite signatures of chronological age, aging, survival, and longevity.

Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk.

Impact of a Whole-Food, High-Soluble Fiber Diet on the Gut-Muscle Axis in Aged Mice.

Previous studies have identified a role for the gut microbiome and its metabolic products, short-chain fatty acids (SCFAs), in the maintenance of muscle mass and physical function (i.e., the gut-muscle axis), but interventions aimed at positively impacting the gut-muscle axis during aging are sparse.

Model organism life extending therapeutics modulate diverse nodes in the drug-gene-microbe tripartite human longevity interactome.

Advances in antiaging drug/lead discovery in animal models constitute a large body of literature on novel senotherapeutics and geroprotectives. However, with little direct evidence or mechanism of action in humans-these drugs are utilized as nutraceuticals or repurposed supplements without proper testing directions, appropriate biomarkers, or consistent models. In this study, we take previously identified drug candidates that have significant evidence of prolonging lifespan and promoting healthy aging in model organisms, and simulate them in human metabolic interactome networks.

A metabolomic signature of the APOE2 allele.

With the goal of identifying metabolites that significantly correlate with the protective e2 allele of the apolipoprotein E (APOE) gene, we established a consortium of five studies of healthy aging and extreme human longevity with 3545 participants. This consortium includes the New England Centenarian Study, the Baltimore Longitudinal Study of Aging, the Arivale study, the Longevity Genes Project/LonGenity studies, and the Long Life Family Study. We analyzed the association between APOE genotype groups E2 (e2e2 and e2e3 genotypes, N = 544), E3 (e3e3 genotypes, N = 2299), and E4 (e3e4 and e4e4 genotypes, N = 702) with metabolite profiles in the five studies and used fixed effect meta-analysis to aggregate the results.

In silico insights into potential gut microbial modulation of NAD+ metabolism and longevity.

Recent evidence has prompted the notion of gut-microbial signatures as an indirect marker of aging and aging-associated decline in humans. However, the underlying host-symbiont molecular interactions contributing to these signatures remain poorly understood. In this study, we address this gap using cheminformatic analyses to elucidate potential gut microbial metabolites that may perturb the longevity-associated NAD+ metabolic network.

Superoxide-mediated oxidative stress accelerates skeletal muscle atrophy by synchronous activation of proteolytic systems.

The maintenance of skeletal muscle mass depends on the overall balance between the rates of protein synthesis and degradation. Thus, age-related muscle atrophy and function, commonly known as sarcopenia, may result from decreased protein synthesis, increased proteolysis, or simultaneous changes in both processes governed by complex multifactorial mechanisms. Growing evidence implicates oxidative stress and reactive oxygen species (ROS) as an essential regulator of proteolysis.

Investigation of the Diet-Gut-Muscle Axis in the Osteoporotic Fractures in Men Study.

Objectives: To investigate the association between dietary fiber density (grams of fiber consumed per 100 kcal) with the gut-muscle axis in older adult men.

Design: Cross-sectional study.

Setting: Osteoporotic Fractures in Men (MrOS) cohort participants at Visit 4 (2014-16).

The Role of the Gut Microbiome on Skeletal Muscle Mass and Physical Function: 2019 Update.

Within the past year, several studies have reported a positive role for the gut microbiome on the maintenance of skeletal muscle mass, evidence that contrasts previous reports of a negative role for the gut microbiome on the maintenance of whole body lean mass. The purpose of this mini-review is to clarify these seemingly discordant findings, and to review recently published studies that further elucidate the gut-muscle axis.

The Kidney-Gut-Muscle Axis in End-Stage Renal Disease is Similarly Represented in Older Adults.

Decreased renal function, elevated circulating levels of urea, intestinal levels of urea-degrading bacteria, and gut-derived uremic metabolites are present in end-stage renal disease (ESRD), a cohort that has reduced muscle mass and physical function, and poor muscle composition. This phenotype, defined as the kidney-gut-muscle axis, is similarly represented in older adults that do not have ESRD. The purpose of this short communication is to illuminate these findings, and to propose a strategy that can positively impact the kidney-gut-muscle axis.

Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults.

Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts.

Papillary Thyroid Cancers with Focal Tall Cell Change are as Aggressive as Tall Cell Variants and Should Not be Considered as Low-Risk Disease.

Background: The tall cell variant of papillary thyroid carcinoma (PTC) is as an aggressive histological variant. The proportion of tall cells needed to influence prognosis is debated.

Methods: Patients with PTC and tall cells, defined as having a height-to-width ratio of ≥ 3:1, seen at a high-volume center between 2001 and 2015, were reviewed.

Impact of Gut Dysbiosis on Neurohormonal Pathways in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a worldwide major health problem. Traditional risk factors for CKD are hypertension, obesity, and diabetes mellitus. Recent studies have identified gut dysbiosis as a novel risk factor for the progression CKD and its complications.

Summer Camp Health Initiative: An Overview of Injury and Illness in Two Canadian Summer Camps.

Introduction: Summer camp is an important part of the lives of millions of youth worldwide. Injuries and illnesses at general residential camps have not been quantified in a Canadian setting. The objective of this study was to examine the incidence of injuries and illnesses that present to camp health centres at two Canadian residential summer camps.

Hemodynamic instability during surgery for pheochromocytoma: comparing the transperitoneal and retroperitoneal approach in a multicenter analysis of 341 patients.

Background: Intraoperative hemodynamic instability is a major challenge during adrenalectomy for pheochromocytoma. Typically, pheochromocytoma is performed laparoscopically either through the retroperitoneal or transperitoneal approach. We aimed to determine if the operative approach affects intraoperative hemodynamic instability during surgery for pheochromocytoma in a large multicenter multicenter cohort.

Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis.

Skeletal muscle is a highly plastic tissue that plays a central role in human health and disease. Aging is associated with a decrease in muscle mass and function (sarcopenia) that is associated with a loss of independence and reduced quality of life. Gut microbiota, the bacteria, archaea, viruses, and eukaryotic microbes residing in the gastrointestinal tract are emerging as a potential contributor to age-associated muscle decline.

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM).

CLINICAL, ULTRASONOGRAPHIC, AND ARTHROSCOPIC CHARACTERISTICS OF HAIR SHAFTS WITHIN SYNOVIAL STRUCTURES OF SEVEN HORSES.

To the authors' knowledge, the ultrasonographic appearance of hair shafts within a synovial structure of the horse has not been described previously. The purpose of this descriptive study was to illustrate the clinical, ultrasonographic, and arthroscopic characteristics of confirmed hair shafts within synovial structures of seven horses. A review of medical records of the Farm and Equine Veterinary Medical Center at North Carolina State University College of Veterinary Medicine identified seven horses with clinical signs suspicious for inflammatory or septic synovitis/tenosynovitis that had hair shafts identified within those structures ultrasonographically.

A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells.

Background: Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA.

Feasibility and safety of lumbosacral epiduroscopy in the standing horse.

Reasons For Performing Study: The large size of the adult horse prevents the use of advanced imaging modalities in most areas of the axial skeleton, including the lumbosacral vertebral column. Traditional imaging techniques are frequently unable to pinpoint the underlying pathology in horses with caudal back pain. In man, lumbosacral epiduroscopy is used to diagnose and treat subjects with chronic back and leg pain.

Metabolites Associated With Circulating Interleukin-6 in Older Adults.

Background: Circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) levels are elevated in older adults, but mechanisms are unclear. In the current study, we used an untargeted metabolomic approach to develop an improved understanding about mechanisms related to circulating IL-6 in older adults.

Methods: Serum IL-6 values were log-transformed to normalize its distribution.

FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES.

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique.