No Significant Effect of Maternal Perception of the Food Environment on Reproductive Success or Pup Outcomes in C57BL/6J Mice.

Objective: Prior work concerning maternal perception of the food environment suggests that perceived disparities in food resources resulted in reduced pup mass and dam reproductive success. This study attempted to replicate this result with increased sample size and additional measures.

Methods: Female C57BL/6J mice (n = 160; 3 weeks old) were randomly assigned to either subject or peer and were pair housed in partitioned cages with olfactory and visual contact.

Analysis of DNA modifications in aging research.

As geroscience research extends into the role of epigenetics in aging and age-related disease, researchers are being confronted with unfamiliar molecular techniques and data analysis methods that can be difficult to integrate into their work. In this review, we focus on the analysis of DNA modifications, namely cytosine methylation and hydroxymethylation, through next-generation sequencing methods. While older techniques for modification analysis performed relative quantitation across regions of the genome or examined average genome levels, these analyses lack the desired specificity, rigor, and genomic coverage to firmly establish the nature of genomic methylation patterns and their response to aging.

Adiposity and Reproductive Cycling Status in Zoo African Elephants.

Objective: The majority of zoo African elephants exhibit abnormal reproductive cycles, but it is unclear why. Acyclicity has been positively associated with body condition scores. The objective of this study was to measure body composition and examine the relationship between adiposity and cyclicity status, mediated by glucose, insulin, leptin, and inflammation.

The development of a specific pathogen free (SPF) barrier colony of marmosets () for aging research.

A specific pathogen free (SPF) barrier colony of breeding marmosets () was established at the Barshop Institute for Longevity and Aging Studies. Rodent and other animal models maintained as SPF barrier colonies have demonstrated improved health and lengthened lifespans enhancing the quality and repeatability of aging research. The marmosets were screened for two viruses and several bacterial pathogens prior to establishing the new SPF colony.

Lithium induces aerobic glycolysis and glutaminolysis in collecting duct principal cells.

Lithium, given to bipolar disorder patients, causes nephrogenic diabetes insipidus (Li-NDI), a urinary-concentrating defect. Li-NDI occurs due to downregulation of principal cell AQP2 expression, which coincides with principal cell proliferation. The metabolic effect of lithium on principal cells, however, is unknown and investigated here.

Retinal gene expression responses to aging are sexually divergent.

Purpose: Sex and age are critical factors in a variety of retinal diseases but have garnered little attention in preclinical models. The current lack of knowledge impairs informed decision making regarding inclusion and design of studies that incorporate both sexes and/or the effects of aging. The goal of this study was to examine normative mouse retina gene expression in both sexes and with advancing age.

Sexually divergent DNA methylation patterns with hippocampal aging.

DNA methylation is a central regulator of genome function, and altered methylation patterns are indicative of biological aging and mortality. Age-related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome-wide analyses of age-related methylation changes have considered the factor of sex in a controlled animal model.

Functional changes in the neural retina occur in the absence of mitochondrial dysfunction in a rodent model of diabetic retinopathy.

Diabetic retinopathy is a neurovascular diabetes complication resulting in vision loss. A wealth of literature reports retinal molecular changes indicative of neural deficits, inflammation, and vascular leakage with chronic diabetes, but the mechanistic causes of disease initiation and progression are unknown. Microvascular mitochondrial DNA (mtDNA) damage leading to mitochondrial dysfunction has been proposed to drive vascular dysfunction in retinopathy.

Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging.

Background: The necessity of including both males and females in molecular neuroscience research is now well understood. However, there is relatively limited basic biological data on brain sex differences across the lifespan despite the differences in age-related neurological dysfunction and disease between males and females.

Methods: Whole genome gene expression of young (3 months), adult (12 months), and old (24 months) male and female C57BL6 mice hippocampus was analyzed.

Sex-dependent Differences in Liver and Gut Metabolomic Profiles With Acarbose and Calorie Restriction in C57BL/6 Mice.

Acarbose, an alpha-glucosidase inhibitor used in treating type 2 diabetes, impairs complex carbohydrate digestion and absorption and extends life span in mice (without a requisite reduction in food intake). To assess sex-differential effects coincident with calorie restriction versus a nonrestricted longevity enhancing intervention, we evaluated the metabolite profiles (by liquid chromatography-mass spectroscopy) from livers and cecal contents of C57BL/6J mice (n = 4/sex/group), which were maintained for 10 months under one of the three diet treatments: ad libitum control diet (CON), ad libitum control diet containing 0.1% acarbose (ACA), or 40% calorie restriction using the control diet (CR).

MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice.

MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3' untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself.

Targeting glucose metabolism for healthy aging.

Advancing age is the greatest single risk factor for numerous chronic diseases. Thus, the ability to target the aging process can facilitate improved healthspan and potentially lifespan. Lack of adequate glucoregulatory control remains a recurrent theme accompanying aging and chronic disease, while numerous longevity interventions result in maintenance of glucoregulatory control.

Contributors to Metabolic Disease Risk Following Spinal Cord Injury.

Spinal cord injury (SCI) induced changes in neurological function have significant impact on the metabolism and subsequent metabolic-related disease risk in injured individuals. This metabolic-related disease risk relationship is differential depending on the anatomic level and severity of the injury, with high level anatomic injuries contributing a greater risk of glucose and lipid dysregulation resulting in type 2 diabetes and cardiovascular disease risk elevation. Although alterations in body composition, particularly excess adiposity and its anatomical distribution in the visceral depot or ectopic location in non-adipose organs, is known to significantly contribute to metabolic disease risk, changes in fat mass and fat-free mass do not fully account for this elevated disease risk in subjects with SCI.

Loss of the antioxidant enzyme CuZnSOD (Sod1) mimics an age-related increase in absolute mitochondrial DNA copy number in the skeletal muscle.

Mitochondria contain multiple copies of the circular mitochondrial genome (mtDNA) that encodes ribosomal RNAs and proteins locally translated for oxidative phosphorylation. Loss of mtDNA integrity, both altered copy number and increased mutations, is implicated in cellular dysfunction with aging. Published data on mtDNA copy number and aging is discordant which may be due to methodological limitations for quantifying mtDNA copy number.

Sex Differences in Lifespan.

Sex differences in longevity can provide insights into novel mechanisms of aging, yet they have been little studied. Surprisingly, sex-specific longevity patterns are best known in wild animals. Evolutionary hypotheses accounting for longevity patterns in natural populations include differential vulnerability to environmental hazards, differential intensity of sexual selection, and distinct patterns of parental care.

Gene-nutrient interaction markedly influences yeast chronological lifespan.

Purpose: Research into the genetic mechanisms of aging has expanded rapidly over the past two decades. This has in part been the result of the use of model organisms (particularly yeast, worms and flies) and high-throughput technologies, combined with a growing interest in aging research. Despite this progress, widespread consensus regarding the pathways that are fundamental to the modulation of cellular aging and lifespan for all organisms has been limited due to discrepancies between different studies.

Bisulfite oligonucleotide-capture sequencing for targeted base- and strand-specific absolute 5-methylcytosine quantitation.

Epigenetic regulation through DNA methylation (5mC) plays an important role in development, aging, and a variety of diseases. Genome-wide studies of base- and strand-specific 5mC are limited by the extensive sequencing required. Targeting bisulfite sequencing to specific genomic regions through sequence capture with complimentary oligonucleotide probes retains the advantages of bisulfite sequencing while focusing sequencing reads on regions of interest, enables analysis of more samples by decreasing the amount of sequence required per sample, and provides base- and strand-specific absolute quantitation of CG and non-CG methylation levels.

Nutrition and energetics in rodent longevity research.

The impact of calorie amount on aging has been extensively described; however, variation over time and among laboratories in animal diet, housing condition, and strains complicates discerning the true influence of calories (energy) versus nutrients on lifespan. Within the dietary restriction field, single macronutrient manipulations have historically been researched as a means to reduce calories while maintaining adequate levels of essential nutrients. Recent reports of nutritional geometry, including rodent models, highlight the impact macronutrients have on whole organismal aging outcomes.

The transcriptional landscape of age in human peripheral blood.

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels.

Accessing Data Resources in the Mouse Phenome Database for Genetic Analysis of Murine Life Span and Health Span.

Understanding the source of genetic variation in aging and using this variation to define the molecular mechanisms of healthy aging require deep and broad quantification of a host of physiological, morphological, and behavioral endpoints. The murine model is a powerful system in which to understand the relations across age-related phenotypes and to identify research models with variation in life span and health span. The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging has performed broad characterization of aging in genetically diverse laboratory mice and has placed these data, along with data from several other major aging initiatives, into the interactive Mouse Phenome Database.

Effects of perfluorocarbon emulsions on microvascular blood flow and oxygen transport in a model of severe arterial gas embolism.

Background: Arterial gas embolism (AGE) is a clinical problem that occurs directly in cardiopulmonary bypass machines in open-heart surgeries, or indirectly (through cardiac or pulmonary right to left shunts) in dive accidents, resulting in serious morbidity and even death. Perfluorocarbon (PFC) emulsions have been used for the treatment of AGE in an animal model. We hypothesized that PFC emulsions enhance microvascular blood flow, speed bubble resolution, and oxygenation in AGE compared with saline in a model of cremaster muscle from anesthetized rats.

A holidic medium for Drosophila melanogaster.

A critical requirement for research using model organisms is a well-defined and consistent diet. There is currently no complete chemically defined (holidic) diet available for Drosophila melanogaster. We describe a holidic medium that is equal in performance to an oligidic diet optimized for adult fecundity and lifespan.

Perfluorocarbon emulsion improves oxygen transport of normal and sickle cell human blood in vitro.

Perfluorocarbons (PFC) are compounds with high gas solubility that could help deliver O2 to tissues and have been suggested as adjunct therapy to ischemia. Using a newly designed in vitro system, we tested the hypothesis that a third generation PFC emulsion (Oxycyte) increased O2 transport of blood by measuring changes in O2 extraction ratio. The system included a computer-controlled pump and blood-gas exchange chambers to oxygenate and deoxygenate the blood from nine sickle cell disease (SCD) patients and five healthy donors.

In vivo microvascular mosaics show air embolism reduction after perfluorocarbon emulsion treatment.

Massive arteriolar gas embolism (AGE) has never been evaluated in vivo using intravital microscopy and previous perfluorocarbon (PFC) emulsions were only effective in AGE when administered before AGE. We implemented a new system for quantitative studies of massive AGE using brightfield microscopy and tested a treatment with a third-generation PFC emulsion after massive AGE. We studied bubble dynamics in cremaster muscles from anesthetized rats after AGE was induced by direct air injection into the femoral artery ipsilateral to the studied muscle.

Re-patterning sleep architecture in Drosophila through gustatory perception and nutritional quality.

Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary factors and sleep behavior in Drosophila melanogaster.