Nonhuman primates (NHP) are important translational models for cardiac aging. To assess progress in this research area and to provide a reference for other investigators, we identified papers indexed in PubMed to determine what species, ages, outcomes, treatments, and approaches have been studied. Since 1983, 33 studies of cardiac aging in NHP have been published. Of these, 27 used species of macaque, 6 baboon, 1 vervet, 1 orangutan, and 1 marmoset (some studies were multispecies). Common research approaches were echocardiography, ECG, and histology of the left ventricle. Only 10 studies performed sex-based analyses. The average age of the oldest macaque studied was 26 y. The reported mean lifespan of macaques in captivity is around 30 y. The age of the oldest baboon studied was 24 y. Baboons in captivity are reported to live on average to 21 y. Twelve studies took a "life course" approach, studying animals of a wide range of ages from less than or equal to 10 y through the late teens to thirties, and employing analyses designed to show change over time. Keeping NHP into old age is a major challenge for biomedical research. The ideal design is to start monitoring in early life and to track how cardiac structure and function change with age. Important issues for future research are an increased focus on life-course approaches, investment in existing life-course NHP cohorts, better reporting of study sample characteristics, more molecular studies to identify genetic risk factors and mechanisms, attention to sex as a biological variable, a move away from descriptive reports to mechanistic studies, development of biomarkers to predict disease risk, and exploration of interventions that are implemented early in life to prevent or delay age-related disease later in life. Reducing exposure to early life adversity, identifying early-life biomarkers of aging and age-related disease, and early treatment can contribute to longer health span.

Macaques with self-injurious behavior (SIB) have been used as a model of human SIB and have previously been shown to respond to treatments targeting enhancement of central serotonin signaling, whether by supplementation with tryptophan, or by inhibiting synaptic reuptake. Decreased serotonin signaling in the brain has also been implicated in many human psychopathologies including major depression disorder. A disturbance in tryptophan metabolism that moves away from the production of serotonin and toward the production of kynurenine has been proposed as a major etiological factor of depression. We hypothesized that in macaques with SIB, central tryptophan metabolism would be shifted toward kynurenine production, leading to lower central serotonin (5-hydroxytryptamine). We analyzed tryptophan metabolites in the cerebral spinal fluid (CSF) of macaques with and without SIB to determine whether and where tryptophan metabolism is altered in affected animals as compared with behaviorally normal controls. We found that macaques with SIB had lower CSF concentrations of serotonin than did behaviorally normal macaques, and that these deficits were inversely correlated with the severity of abnormal behavior. However, our results suggest that this decrease is not due to shifting of the tryptophan metabolic pathway toward kynurenine, as concentrations of kynurenine were also low. Concentrations of IL6 were elevated, suggesting central inflammation. Determining the mechanism by which serotonin function is altered in self-injurious macaques could shed light on novel therapies for SIB and other disorders of serotonin signaling.

Murine astrovirus 2 (MuAstV2) is a novel murine astrovirus recently identified in laboratory and wild mice. MuAstV2 readily transmits between immunocompetent mice yet fails to transmit to highly immunocompromised mouse strains—a unique characteristic when contrasted with other murine viruses including other astroviruses. We characterized the viral shedding kinetics and tissue tropism of MuAstV2 in immunocompetent C57BL/6NCrl mice and evaluated the apparent resistance of highly immunocompromised NOD- Prkdc^em26Cd52Il2rg^em26Cd22 /NjuCrl mice to MuAstV2 after oral inoculation. Temporal patterns of viral shedding were determined by serially measuring fecal viral RNA. Tissue tropism and viral load were characterized and quantified by using in-situ hybridization (ISH) targeting viral RNA. Cellular tropism was characterized by evaluating fluorescent colocalization of viral ISH with various immunohistochemical markers. We found a rapid increase of fecal viral RNA in B6 mice, which peaked at 5 d after inoculation (dpi) followed by cessation of shedding by 168 dpi. The small intestine had the highest percentage of hybridization (3.09% of tissue area) of all tissues in which hybridization occurred at 5 dpi. The thymus displayed the next highest degree of hybridization (2.3%) at 7 dpi, indicating extraintestinal viral spread. MuAstV2 RNA hybridization was found to colocalize with only 3 of the markers evaluated: CD3 (T cells), Iba1 (macrophages), and cytokeratin (enterocytes). A higher percentage of CD3 cells and Iba1 cells hybridized with MuAstV2 as compared with cytokeratin at 2 dpi (CD3, 59%; Iba1, 46%; cytokeratin, 6%) and 35 dpi (CD3, 14%; Iba1, 55%; cytokeratin, 3%). Neither fecal viral RNA nor viral hybridization was noted in NCG mice at the time points examined. In addition, mice of mixed genetic background were inoculated, and only those with a functioning Il2rg gene shed MuAstV2. Results from this study suggest that infection of, or interaction with, the immune system is required for infection by or replication of MuAstV2.

Gastrointestinal microbiota are affected by a wide variety of extrinsic and intrinsic factors. In the husbandry of laboratory mice and design of experiments, controlling these factors where possible provides more reproducible results. However, the microbiome is dynamic, particularly in the weeks immediately after weaning. In this study, we characterized the baseline gastrointestinal microbiota of immunocompromised mice housed under standard conditions for our facility for 6 weeks after weaning, with housing either in an isolator or in individually ventilated cages and a common antibiotic diet (trimethoprim sulfamethoxazole). We compared these conditions to a group fed a standard diet and a group that was weaned to a standard diet then switched to antibiotic diet after 2 weeks. We found no clear effect of diet on richness and α diversity of the gastrointestinal microbiota. However, diet did affect which taxa were enriched at the end of the experiment. The change to antibiotic diet during the experiment did not convert the gastrointestinal microbiome to a state similar to mice consistently fed antibiotic diet, which may highlight the importance of the initial post-weaning period in the establishment of the gastrointestinal microbiome. We also observed a strong effect of housing type (isolator compared with individually ventilated cage) on the richness, α diversity, β diversity, and taxa enriched over the course of the experiment. Investigating whether the diet or microbiome affects a certain strain's phenotype is warranted in some cases. However, our findings do not suggest that maintaining immunocompromised mice on antibiotic feed has a clinical benefit when potential pathogens are operationally excluded, nor does it result in a more consistent or controlled microbiome in the post-weaning period.

Disturbances in the gut microbiota are known to be associated with numerous human diseases. Mice have proven to be an invaluable tool for investigating the role of the gut microbiota in disease processes. Nonexperimental factors related to maintaining mice in the laboratory environment are increasingly being shown to have inadvertent effects on the gut microbiota and may function as confounding variables. Microisolation technique is a term used to describe the common biosecurity practice of spraying gloved hands with disinfectant before handling research mice. This practice prevents contamination with pathogenic microorganisms. To investigate if exposure to disinfectants can affect the mouse gut microbiota, C57BL/6 mice were exposed daily for 27 consecutive days to commonly used laboratory disinfectants through microisolation technique. The effects of 70% ethanol and disinfectant products containing chlorine dioxide, hydrogen peroxide, or potassium peroxymonosulfate were each evaluated. Fecal pellets were collected after 7, 14, 21, and 28 d of disinfectant exposure, and cecal contents were collected at day 28. DNA extractions were performed on all cecal and fecal samples, and microbial community structure was characterized using 16S ribosomal RNA amplicon sequencing. Alpha and β diversity metrics and taxon-level analyses were used to evaluate differences in microbial communities. Disinfectant had a small but significant effect on fecal microbial communities compared with sham-exposed controls, and effects varied by disinfectant type. In general, longer exposure times resulted in greater changes in the fecal microbiota. Effects on the cecal microbiota were less pronounced and only seen with the hydrogen peroxide and potassium peroxymonosulfate disinfectants. These results indicate that laboratory disinfectant use should be considered as a potential factor that can affect the mouse gut microbiota.

Murine norovirus (MNV), which can be used as a model system to study human noroviruses, can infect macrophages/ monocytes, neutrophils, dendritic, intestinal epithelial, T and B cells, and is highly prevalent in laboratory mice. We previously showed that MNV infection significantly reduces bone marrow B cell populations in a Stat1-dependent manner. We show here that while MNV-infected Stat1^–/– mice have significant losses of bone marrow B cells, splenic B cells capable of mounting an antibody response to novel antigens retain the ability to expand. We also investigated whether increased granulopoiesis after MNV infection was causing B cell loss. We found that administration of anti-G-CSF antibody inhibits the pronounced bone marrow granulopoiesis induced by MNV infection of Stat1^–/– mice, but this inhibition did not rescue bone marrow B cell losses. Therefore, MNV-infected Stat1^–/– mice can still mount a robust humoral immune response despite decreased bone marrow B cells. This suggests that further investigation will be needed to identify other indirect factors or mechanisms that are responsible for the bone marrow B cell losses seen after MNV infection. In addition, this work contributes to our understanding of the potential physiologic effects of Stat1-related disruptions in research mouse colonies that may be endemically infected with MNV.

In this case study, 15 adult laboratory Xenopus (Silurana) tropicalis (7 adult males and 8 adult females) were examined for nodular enlargements of the clawed digits (digits 0, I, II, and III) on the hind feet. Radiographs showed smoothly margined, rounded, peripherally mineralized lesions arising from the distal phalanges of digits 0-III with osteoproductive and osteolytic components in all frogs. Micro computed tomography (microCT) scans further revealed interphalangeal (IP), metacarpophalangeal (MCP), and metatarsophalangeal (MTP) joint osteoarthritis characterized by periarticular new bone formation, rounded mineral foci both peripherally and centrally within the joints, and more rarely, linear mineralization palmar/plantar to the joints in the flexor tendons. In the nonclawed digits, the shape of the distal phalanx was variably distorted and both subluxation and malangulation of IP joints were identified. Histologically, nodules corresponded to a peripheral rim of mature cortical bone surrounding central adipose tissue, scattered hematopoietic elements, and residual bone of the distal phalanx. Occasionally, the peripheral rim of cortical bone extended proximally to encompass the distal aspect of adjacent phalanx. MCP, MTP and IP joint spaces of most digits exhibited widespread osteoarthritis characterized by periarticular cartilaginous or osseous metaplasia, bony remodeling, and less frequently, granulomatous osteomyelitis. Nutritional analyses of the feed did not indicate imbalances nor were the lesions consistent with metabolic bone disease. The exact etiopathogenesis of these lesions is unknown; however, we hypothesize that the osteoarthritic changes are due to a combination of the frogs' mature age, the unique structure of the Xenopus spp. claw, genetics and biomechanical forces on the digits and distal phalanges of the hind feet.