Evaluating instruments for assessing healthspan: a multi-center cross-sectional study on health-related quality of life (HRQL) and frailty in the companion dog.

Developing valid tools that assess key determinants of canine healthspan such as frailty and health-related quality of life (HRQL) is essential to characterizing and understanding aging in dogs. Additionally, because the companion dog is an excellent translational model for humans, such tools can be applied to evaluate gerotherapeutics and investigate mechanisms underlying longevity in both dogs and humans. In this multi-center, cross-sectional study, we investigated the use of a clinical questionnaire (Canine Frailty Index; CFI; Banzato et al., 2019) to assess frailty and an owner assessment tool (VetMetrica HRQL) to evaluate HRQL in 451 adult companion dogs. Results demonstrated validity of the tools by confirming expectations that frailty score increases and HRQL scores deteriorate with age. CFI scores were significantly higher (higher frailty) and HRQL scores significantly lower (worse HRQL) in old dogs (≥ 7 years of age) compared to young dogs (≥ 2 and < 6 years of age). Body size (small < 11.3 kg (25 lbs) or large > 22.7 kg (50 lbs)) was not associated with CFI or total HRQL score. However, older, larger dogs showed faster age-related decline in HRQL scores specific to owner-reported activity and comfort. Findings suggest that the clinician-assessed CFI and owner-reported VetMetrica HRQL are useful tools to evaluate two determinants of healthspan in dogs: the accumulation of frailty and the progressive decline in quality of life. Establishing tools that operationalize the assessment of canine healthspan is critical for the advancement of geroscience and the development of gerotherapeutics that benefit both human and veterinary medicine. Graphical summary of the design, results, and conclusions of the study.

Evaluation of geriatric trauma in dogs with moderate to severe injury (6169 cases): A VetCOT registry study.

OBJECTIVE: To examine geriatric classification as a predictor of survival in moderate to severely injured dogs denoted by animal trauma triage (ATT) scores ≥3 or modified Glasgow Coma Scale (mGCS) scores ≤14. DESIGN: Retrospective observational cohort study utilizing data collected between September 2013 and May 2019 with follow-up until death or hospital discharge. SETTING: Thirty-one trauma centers including university teaching hospitals and private referral centers. ANIMALS: A total of 6169 dogs entered into the Veterinary Committee on Trauma Registry with complete data entry including age, weight, outcome, mGCS (≤14), and/or ATT (≥3). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The effect of geriatric classification on survival was estimated using shared-frailty cox proportional hazard models. Model 1 dependent variables: death despite intervention or euthanasia due to grave prognosis. Model 2 dependent variables: death by euthanasia due to financial influence or combined influence of finances and grave prognosis. Model 3 evaluated interactions between geriatric classification and moderate versus severe trauma. The shared-frailty models controlled for contributing site as a random effect and other confounding variables, including trauma severity. Model 1: geriatrics had a significantly increased hazard risk (HR) for death (HR = 1.48, P < 0.0001). Model 2: geriatrics had an insignificant increased HR for death (HR = 1.34, P = 0.08). Model 3: geriatrics demonstrated significantly increased mortality risk with moderate level trauma. Additional Model 1 variables independently associated with mortality include ATT perfusion, neurologic, respiratory subscores, mGCS motor subscore, weight, and spinal trauma. Additional Model 2 variables independently associated with mortality include ATT perfusion subscore and neuter status. In general, statistical differences between cohorts were found with regard to lactate, PCV, total protein, and glucose. CONCLUSIONS: Among moderately injured dogs who experienced death despite intervention or euthanasia due to grave prognosis, mortality risk is significantly higher in geriatrics as compared to nongeriatrics.

An open science study of ageing in companion dogs.

The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan. To take advantage of this opportunity, the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples. Here, we describe the specific goals and design of the Dog Aging Project and discuss the potential for this open-data, community science study to greatly enhance understanding of ageing in a genetically variable, socially relevant species living in a complex environment.

Invited review: Milk fat globule membrane-A possible panacea for neurodevelopment, infections, cardiometabolic diseases, and frailty.

Milk is an evolutionary benefit for humans. For infants, it offers optimal nutrients for normal growth, neural development, and protection from harmful microbes. Humans are the only mammals who drink milk throughout their life. Lipids in colostrum originate mostly from milk fat globule membrane (MFGM) droplets extruded from the mammary gland. The MFGM gained much interest as a potential nutraceutical, due to their high phospholipid (PL), ganglioside (GD), and protein contents. In this review, we focused on health effects of MFGM ingredients and dairy food across the life span, especially on neurodevelopment, cardiometabolic health, and frailty in older adults. The MFGM supplements to infants and children reduced gastrointestinal and respiratory tract infections and improved neurodevelopment due to the higher content of protein, PL, and GD in MFGM. The MFGM formulas containing PL and GD improved brain myelination and fastened nerve conduction speed, resulting in improved behavioral developments. Administration of MFGM-rich ingredients improved insulin sensitivity and decreased inflammatory markers, LDL-cholesterol, and triglycerides by lowering intestinal absorption of cholesterol and increasing its fecal excretion. The MFGM supplements, together with exercise, improved ambulatory activities, leg muscle mass, and muscle fiber velocity in older adults. There are great variations in the composition of lipids and proteins in MFGM products, which make comparisons of the different studies impossible. In addition, investigations of the individual MFGM components are required to evaluate their specific effects and molecular mechanisms. Although we are currently only beginning to understand the possible health effects of MFGM products, the current MFGM supplementation trials as presented in this review have shown significant clinical health benefits across the human life span, which are worth further investigation.

Nutritional Concerns for Cancer, Cachexia, Frailty, and Sarcopenia in Canine and Feline Pets.

Cachexia and frailty can be described as independent entities yet are interrelated as constituents of malnutrition and the aging process. The unifying aspect is lean muscle loss, ultimately driven by inflammation and the adverse ramifications to pets with chronic, debilitating, or terminal disease states, including cancer. Modification to intake of dietary protein, fat, omega-3 fatty acids, and selected vitamins has shown benefit in management protocols as preventative and palliative care, but further investigation is imperative.

A Frailty Index based on clinical data to quantify mortality risk in dogs.

Frailty is defined as a decline in an organism's physiological reserves resulting in increased vulnerability to stressors. In humans, a single continuous variable, the so-called Frailty Index (FI), can be obtained by multidimensionally assessing the biological complexity of an ageing organism. Here, we evaluate this variability in dogs and compare it to the data available for humans. In dogs, there was a moderate correlation between age and the FI, and the distribution of the FI increased with age. Deficit accumulation was strongly related to mortality. The effect of age, when combined with the FI, was negligible. No sex-related differences were evident. The FI could be considered in epidemiological studies and/or experimental trials to account for the potential confounding effects of the health status of individual dogs. The age-related deficit accumulation reported in dogs is similar to that demonstrated in humans. Therefore, dogs might represent an excellent model for human aging studies.

Evaluation of a low-technology system to obtain morphological and mobility trial measurements in dogs and investigation of potential predictors of canine mobility.

OBJECTIVE: To develop a low-technology system that can be used by dog owners to obtain morphological and mobility measurements in companion dogs as candidate components of an eventual canine frailty scale. ANIMALS: 57 adult (≥ 1-year-old) dogs enrolled by 43 owners. PROCEDURES: Morphological measurements of dogs were performed by investigators and dog owners. Dogs participated in timed in-clinic mobility trials across a flat surface (on-leash trial with the owner, on-leash trial with the investigator, and off-leash trial) and on stairs; each trial was repeated 3 times. Owners were asked to conduct a second stair trial at home 2 weeks later. Agreement between owner- and investigator-obtained measurements was assessed with Shrout-Fleiss intraclass correlation coefficients and paired t tests. Age, quartile of projected percentage of mean life span attained (adjusted for body weight), and height were evaluated as predictors of speed and stride length in mobility trials with linear regression and Spearman rank correlation analysis. RESULTS: Agreement between owner- and investigator-obtained morphological measurements was strong. Age was a weak but significant predictor of decreased dog speed in mobility trials (adjusted R2, 0.10 to 0.23). Speed decreased significantly with increasing quartile of projected life span attained. A linear regression model that included height and age predicted dog speed better than models with age or height alone. CONCLUSIONS AND CLINICAL RELEVANCE: Morphological and mobility trial measurements can be obtained by dog owners with minimal training. Low-technology measurements of mobility trial speed offer potential as components in a future scoring scale for canine frailty.

Identifying and Implementing Endpoints for Geriatric Mice.

The types of changes in physical appearance and behavior that occur in elderly people similarly develop in elderly animals. Signs and symptoms that might cause concern in younger people or mice may be normal in their elderly but generally healthy counterparts. Although numerous scoring methods have been developed to assess rodent health, these systems were often designed for young adults used in specific types of research, such as cancer or neurologic studies, and therefore may be suboptimal for assessing aging rodents. Approaches known as frailty assessments provide a global evaluation of the health of aged mice, rats, and people, and mouse frailty scores correlate well with the likelihood of death. Complementing frailty assessment, prediction of imminent death in aged mice can often be accomplished by focusing on 2 objective parameters-body weight and temperature. Before they die, many (but not all) mice develop marked reductions in body weight and temperature, thus providing signs that close monitoring, intervention, or preemptive euthanasia may be necessary. Timely preemptive euthanasia allows antemortem collection of data and samples that would be lost if spontaneous death occurred; preemptive euthanasia also limits terminal suffering. These approaches to monitoring declining health and predicting death in elderly research mice can aid in establishing and implementing timely interventions that both benefit the research and reduce antemortem suffering.

Caloric Restriction and Healthy Life Span: Frail Phenotype of Nonhuman Primates in the Wisconsin National Primate Research Center Caloric Restriction Study.

Calorie restriction without malnutrition increases longevity and delays the onset of age-associated disorders in multiple species. Recently, greater emphasis has been placed on healthy life span and preventing frailty than on longevity. Here, we show the beneficial effect of long-term calorie restriction on frailty in later life in a nonhuman primate. Frail phenotypes were evaluated using metabolic and physical activity data and defined using the Fried index. Shrinking was defined as unintentional weight loss of greater than 5% of body weight. Weakness was indicated by decline in high intensity spontaneous physical activity. Poor endurance or exhaustion was indicated by a reduction in energy efficiency of movements. Slowness was indicated by physical activity counts in the morning. Low physical activity level was measured by total energy expenditure using doubly labeled water divided by sleeping metabolic rate. Weakness, poor endurance, slowness, and low physical activity level were significantly higher in control compared with calorie restriction (p < .05) as was total incidence of frailty (p < .001). In conclusion, we established a novel set of measurable criteria of frailty in nonhuman primates, and using these criteria, showed that calorie restriction reduces the incidence of frailty and increases healthy life span in nonhuman primates.