Banking on a new understanding: translational opportunities from veterinary biobanks.

Current advances in geroscience are due in part to the discovery of biomarkers with high predictive ability in short-lived laboratory animals such as flies and mice. These model species, however, do not always adequately reflect human physiology and disease, highlighting the need for a more comprehensive and relevant model of human aging. Domestic dogs offer a solution to this obstacle, as they share many aspects not only of the physiological and pathological trajectories of their human counterpart, but also of their environment. Furthermore, they age at a considerably faster rate. Studying aging in the companion dog provides an opportunity to better understand the biological and environmental determinants of healthy lifespan in our pets, and to translate those findings to human aging. Biobanking, the systematic collection, processing, storage, and distribution of biological material and associated data has contributed to basic, clinical, and translational research by streamlining the management of high-quality biospecimens for biomarker discovery and validation. In this review, we discuss how veterinary biobanks can support research on aging, particularly when integrated into large-scale longitudinal studies. As an example of this concept, we introduce the Dog Aging Project Biobank.

Canine hyperadrenocorticism associations with signalment, selected comorbidities and mortality within North American veterinary teaching hospitals.

OBJECTIVE: To describe a large population of dogs with a diagnosis of hyperadrenocorticism at the time of death in North American veterinary teaching hospitals, and to identify comorbid conditions associated with hyperadrenocorticism. MATERIALS AND METHODS: Retrospective cohort study of 1519 dogs with hyperadrenocorticism from a population of 70,574 dogs reported to the Veterinary Medical Database. Signalment, presence or absence of hyperadrenocorticism, aetiology of hyperadrenocorticism (if described), frequency of select comorbidities and causes of death were evaluated in dogs with and without hyperadrenocorticism. RESULTS: Hyperadrenocorticism was more frequent in females. Neutering was associated with a minor, but significant, increase in the odds of hyperadrenocorticism. Hyperadrenocorticism was the presumed cause of death of 393 (25∙9%) of affected dogs. When aetiology was specified (527 dogs, corresponding to 34∙7% of the cases), pituitary-dependent hyperadrenocorticism [387 (73∙4%) out of 527 dogs] was more common than functional adrenocortical tumour [136 (25∙8%) out of 527 dogs). Hyperadrenocorticism was over-represented in certain expected (miniature poodle, dachshund) and unexpected (Irish setter, bassett hound) breeds compared with the population at large. Of the select comorbidities investigated, dogs with hyperadrenocorticism were at increased risk for concurrent diabetes mellitus, urinary tract infection, urolithiasis, hypertension, gall bladder mucocoele and thromboembolic disease compared with dogs without hyperadrenocorticism. CLINICAL SIGNIFICANCE: Hyperadrenocorticism is significantly associated with certain comorbid conditions but is not a major cause of mortality in affected dogs. Documented patterns now provide targets for prospective clinical research.

The impacts of Wolbachia and the microbiome on mate choice in Drosophila melanogaster.

Symbionts and parasites can manipulate their hosts' reproduction to their own benefit, profoundly influencing patterns of mate choice and evolution of the host population. Wolbachia is one of the most widespread symbionts among arthropods, and one that alters its hosts' reproduction in diverse and dramatic ways. While we are beginning to appreciate how Wolbachia's extreme manipulations of host reproduction can influence species diversification and reproductive isolation, we understand little about how symbionts and Wolbachia, in particular, may affect intrapopulation processes of mate choice. We hypothesized that the maternally transmitted Wolbachia would increase the attractiveness of its female hosts to further its own spread. We therefore tested the effects of Wolbachia removal and microbiome disruption on female attractiveness and male mate choice among ten isofemale lines of Drosophila melanogaster. We found variable effects of general microbiome disruption on female attractiveness, with indications that bacteria interact with hosts in a line-specific manner to affect female attractiveness. However, we found no evidence that Wolbachia influence female attractiveness or male mate choice among these lines. Although the endosymbiont Wolbachia can greatly alter the reproduction of their hosts in many species, there is no indication that they alter mate choice behaviours in D. melanogaster.

Mortality in north american dogs from 1984 to 2004: an investigation into age-, size-, and breed-related causes of death.

BACKGROUND: Anecdotal beliefs and limited research suggest variable patterns of mortality in age, size, and breed cohorts of dogs. Detailed knowledge of mortality patterns would facilitate development of tailored health-maintenance practices and contribute to the understanding of the genetic basis of disease. HYPOTHESIS/OBJECTIVES: To describe breed-specific causes of death in all instances of canine mortality recorded in the Veterinary Medical Database (VMDB)(a) between 1984 and 2004. We hypothesized that causes of death, categorized by organ system (OS) or pathophysiologic process (PP), would segregate by age, body mass, and breed. ANIMALS: 74,556 dogs from the VMDB for which death was the outcome of the recorded hospital visit. METHODS: Retrospective study. Causes of death from abstracted VMDB medical records were categorized by OS and PP and analyzed by age, breed, and breed-standard mass of dog. RESULTS: Causes of death, categorized by OS or PP, segregated by age, breed, and breed-standard mass. Young dogs died more commonly of gastrointestinal and infectious causes whereas older dogs died of neurologic and neoplastic causes. Increasing age was associated with an increasing risk of death because of cardiovascular, endocrine, and urogenital causes, but not because of hematopoietic or musculoskeletal causes. Dogs of larger breeds died more commonly of musculoskeletal and gastrointestinal causes whereas dogs of smaller breeds died more commonly of endocrine causes. CONCLUSIONS AND CLINICAL IMPORTANCE: Not all causes of death contribute equally to mortality within age, size, or breed cohorts. Documented patterns now provide multiple targets for clinical research and intervention.

Alternative measures of response to Pseudomonas aeruginosa infection in Drosophila melanogaster.

Studies of invertebrate immune defence often measure genetic variation either for the fitness cost of infection or for the ability of the host to clear the parasite. These studies assume that variation in measures of resistance is related to variation in fitness costs of infection. To test this assumption, we infected strains of the fruit fly, Drosophila melanogaster, with a pathogenic bacterium. We then measured the correlation between host bacterial load and the ability to survive infection. Despite the presence of genotypic variation for both traits, bacterial load and survival post-infection were not correlated. Our results support previous arguments that individual measures of immune function and the host's ability to survive infection may be decoupled. In light of these results, we suggest that the difference between tolerance and resistance to infection, a distinction commonly found in the plant literature, may also be of value in studies of invertebrate immunity.

Age-specific changes in epistatic effects on mortality rate in Drosophila melanogaster.

Models for the evolution of senescence assume that genes with age-specific effects act independently of one another. Although recent empirical data show that longevity is influenced in part by interactions between genes, there are currently few data on whether epistasis influences age-specific components of mortality. To gauge if and how interactions affect age-specific traits, we incorporated the Drosophila visible marker mutations ebony, forked, and purple into seven wild-caught strains of D. melanogaster to examine gene x genetic background interactions. We found significant natural genetic variation for longevity and baseline mortality rates. Gene x genetic background interactions were prevalent not only for longevity but also for baseline mortality rates and age-specific mortality rates. We conclude that gene x genetic background epistasis is prevalent for aging-related traits and could play a significant role in the evolution of aging. These results suggest that future genetic models for the evolution of aging should incorporate the effects of epistasis.

Quantitative genetic tests of recent senescence theory: age-specific mortality and male fertility in Drosophila melanogaster.

Quantitative genetic models of aging predict that additive genetic variance for fitness components should increase with age. However, recent studies have found that at very late ages, the genetic variance components decline. This decline may be due to an age-related drop in reproductive effort. If genetic variance in reproductive effort affects the genetic variance in mortality, the decline in reproductive effort at late ages should lead to a decrease in the genetic variance in mortality. To test this, we carried out a large-scale quantitative genetic analysis of age-specific mortality and fertility in virgin male Drosophila melanogaster. As in earlier studies, we found that the additive variance for age-specific mortality and fertility declined at late ages. Also, recent theoretical developments provide new predictions to distinguish between the mutation accumulation (MA) and antagonistic pleiotropy (AP) models of senescence. The deleterious effects of inbreeding are expected to increase with age under MA, but not under AP. This prediction was supported for both age-specific mortality and male fertility. Under AP, the ratio of dominance to additive variance is expected to decline with age. This predicition, too, was supported by the data analyzed here. Taken together, these analyses provide support for both the models playing a role in the aging process. We argue that the time has come to move beyond a simple comparison of these genetic models, and to think more deeply about the evolutionary causes and consequences of senescence.