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Studying longevity and morbidity in giant and small breeds of dogs
Abstract
Is it true that the bigger the dog, the shorter the life? Using 10 years of data, these veterinarians studied that supposition, and looked at the types of diseases that afflict older dogs of extreme body sizes.
... The latter was tested by comparing and contrasting two companion animal species that exist in similar environments (cat and dog) and also, within dog, comparing dogs of different body weight. The latter was investigated as size in dog has a wide-ranging impact, effecting, for example, mitochondrial function (10,11), disease predisposition (12)(13)(14) and lifespan (15,16). To summarise, the objective of this research was to identify A c c e p t e d M a n u s c r i p t evidence-based canine and feline life stages based on medical phenotypes from electronic medical records. ...
... Similarly, compared to previously published charts defining canine life stages by breed size (36,37), even with the differing weights used to define breed size, the results from this study define 'Senior' and 'Super Senior' at noticeably later ages than previously defined for the equivalent stages ('Senior' and 'Geriatric'). We also noted that the smaller sized dogs classified as senior 2 years later than larger dogs, consistent with them simply living longer (15,16) and also having an extended healthspan, potentially due to mitochondrial bienenergetics (11). Differences to previous approaches may reflect that we only considered one aspect of aging, that of development of disease conditions, and not including characteristics described in other life stage guidelines (behavioural/psychologic and physical characteristics, such as lean tissue and activity levels). ...
Aging is a complex, multifactorial process, where different life stages reflect changes in metabolic processes, immune capacities and genetic/epigenetic repertoires. With accumulating exposure to environmental stresses and deterioration of physiological functions, body systems become more prone to low-grade chronic inflammation and an increasing range of pathologies. We hypothesised that differential susceptibility to diseases across lifespan reflect phased changes in an organism’s physiological capacity that may highlight when interventions may be appropriately used. Furthermore, the number of life stages may vary between species and be impacted by signalment such as breed. We tested this hypothesis using disease diagnoses data from veterinary electronic medical records containing almost two million cats and over four million dogs.
Bi-clustering (on rates of disease diagnoses) and adaptive branch pruning were used to identify age clusters that could be used to define adult life stages. Clustering amongst diagnoses were then interpreted within the context of each defined life stage. The analyses identified five age clusters in cats and four age clusters within each of the four canine breed size categories used.
This study, using population scale data for two species, one with differential size and life expectancies, is the first to our knowledge to use disease diagnosis data to define adult life stages. The life stages presented here are a result of a data-driven approach to age and disease stratification and are intended to support conversations between clinicians and clients about appropriate healthcare recommendations.
... Therefore, PEPCK activity may be greater in primary fibroblasts from large breeds because these breeds may grow for longer periods of time than small breeds (Jimenez 2016). Large dog breeds are more prone to developing diseases such as cancer (Deeb and Wolf 1996), so PEPCK activity may play a role in this phenotype. We also expected to see decreased PEPCK activity in primary fibroblasts and plasma with age because PEPCK can promote mitochondrial respiration (Feng et al. 2016), but we did not find a significant relationship with age in primary fibroblasts. ...
Animals produce ATP through oxidative phosphorylation using oxygen, but cellular energy can also be obtained through glycolysis when oxygen is not present at sufficient levels. Although most mammals of larger body mass have longer life spans, small dog breeds tend to outlive large breeds. Primary fibroblast cells from larger breeds of dogs have previously been shown to have increased dependency on glycolytic phenotypes across their lifespan. Different levels of activity of the glycolytic enzymes pyruvate kinase (PK), lactate dehydrogenase (LDH), and phosphoenolpyruvate carboxykinase (PEPCK) may provide insight to a mechanism that leads to the different metabolic phenotype observed in different sized breeds as they age. In this study, 1) we measured the activities of PK, LDH, and PEPCK in primary fibroblasts from dogs of different breed sizes and age classes and 2) measured the activities of PK and LDH in plasma from dogs of different breed sizes and age classes. We found that there was no significant relationship between body mass and PK, LDH and PEPCK activity in primary fibroblasts. Further, there were not significant differences with activity in these enzymes for old dogs compared to young dogs. In plasma, we found a negative correlation between PK activity and body mass and no relationship between LDH activity and body mass. There was a negative relationship between LDH activity and age in dogs. Further, while a negative correlational relationship between PK activity and age was only marginal, a best subsets regression model demonstrated a significant marginal effect of age on PK activity. PK and LDH may provide intermediates for other metabolic pathways in small breeds. However, large breed dogs may demonstrate a deficiency in metabolism at the PK level, a cellular metabolic pathway that may potentially aid in tumor progression.
... The concept of vigor is logically translatable to aging dogs, but there lacks a validated process to divide aging populations into the progressive categories of fun, functionality, frailty, and failure (Figure 1). Furthermore, unlike people, the breed and size of the dog plays an important role in suggesting the onset of old age with most giant breeds defined as geriatric at 7 years while small breeds take up to 12 years (11,12). For an individual within any age and canine size cohort, the natural aim would be to maximize the vigor score. ...
Geriatric animals account for half of the pet population in the United States with their numbers increasing annually. Furthermore, a significant percentage of veterinary patients with movement limitations could be grossly categorized as geriatric and living within the end stage of their predicted lifespans. Because mobility is correlated to quality of life and time to death in aging dogs, a major goal in optimizing canine geriatric health is to improve functional movement. Within the geriatric population, identifying disabilities that affect daily living and quality of life may be used by the rehabilitation practitioner to provide stronger prognoses, treatment goals, and outcome measures. Examples of such means are described within this review. In human medicine, the concept of “optimal aging”, or “healthy aging”, has emerged in which inevitable detrimental age-related changes can be minimized or avoided at various levels of physical, mental, emotional, and social health. Both environment and genetics may influence aging. Identifying and improving environmental variables we can control remain a key component in optimizing aging. Furthermore, diagnosing and treating age related comorbidities common to older populations allows for improved quality of life and is often directly or indirectly affecting mobility. Obesity, sarcopenia, and a sedentary lifestyle are a trifecta of age-related morbidity common to both people and dogs. Healthy lifestyle choices including good nutrition and targeted exercise play key roles in reducing this morbidity and improving aging. Disablement models act as essential tools for creating more effective physiotherapy plans in an effort to counter dysfunction and disability. Within these models, functional testing represents a standard and validated means of scoring human geriatric function as well as monitoring response to therapy. Because of the great need in dogs, this review aims to provide a reasonable and testable standardized framework for canine functional scoring. We believe a complete assessment of canine geriatric patients should comprise of identifying environmental variables contributing to health status; diagnosing comorbidities related to disease and aging; and characterizing disability with standardized methods. Only through this process can we construct a comprehensive, reasonable, and targeted rehabilitation plan with appropriate follow up aimed at healthy aging.
... With whole-animal correlations to aging rates only recently established (Deeb and Wolf 1994;Patronek et al. 1997;Michell 1999), progress toward a mechanistic approach to answer the inevitable query of slow aging rates in small dogs with high mass-specific metabolic rates remains challenging. Some have postulated that faster growth rates in large breed dogs could lead them to be burdened with increases in oxidative damage during early life, leading to higher rates of diseases associated with free radical damage, and hence, early mortality (Galis et al. 2007;Kraus et al. 2013). ...
The rich history and global abundance of domestic dogs (Canis familiaris) present a unique opportunity and an ideal model for interdisciplinary research. Canine evolutionary history demonstrates unprecedented changes across all levels of biological organization. These include diversification from highly social, pack-dwelling wild carnivores (extant gray wolves, C. lupus), to increased dependence on humans (domestication), to modern in-home colonization featuring close physical proximity to humans (interspecies bonding). The young, emerging field of “canine science” comprises diverse biological disciplines including evolution, genetics, cognition, behavior, physiology, comparative medicine, and ecology, drawing on studies of both natural and experimental systems and scaling across all levels of biological organization, from genomes to ecosystems. However, limited connections bridge the various fields associated with canine science, although in every branch it is recognized that this species is one of the most phenotypically variable mammals. Yet there has been growing interest in integrating the insights from genomic evolution with those from ecophysiology and ecology, thus facilitating a more biologically comprehensive perspective of dogs. In particular, integrative, mechanistic, and/or ecological studies have been generally underrepresented. To address these emerging interests, we have collected the most compelling questions in the field of canine biology and present avenues of current and future research. This paper serves to both orient the reader to this special issue, as well as offer a forward-looking perspective from diverse biological sub-disciplines to highlight current and future goals in canine research.
... Dogs present an interesting physiological challenge: smaller dogs tend to live significantly longer than larger dogs across all breeds [18,28,38,46,55], opposing patterns generally found across mammalian species. Underlying physiological mechanisms for this pattern have only begun to be unraveled. ...
Small breed dogs have longer lifespans than their large breed counterparts. Previous work demonstrated that primary fibroblast cells isolated from large breed young and old dogs have a persistent glycolytic metabolic profile compared with cells from small breed dogs. Here, we cultured primary fibroblast cells from small and large, young and old dogs and treated these cells with three commercially available drugs that show lifespan and health span benefits, and have been shown to reduce glycolytic rates: rapamycin (rapa), resveratrol (res) and metformin (met). We then measured aerobic and anaerobic cellular respiration in these cells. We found that rapa and res increased rates of non-glycolytic acidification in small and large breed puppies and basal oxygen consumption rates (OCR) in small and large breed puppies. Rapa increased proton leak and non-mitochondrial respiration in small and large breed puppies. Maximal respiration was significantly altered with rapa treatment but in opposing ways: large breed puppies showed a significant increase in maximal respiration when treated with rapa, and small old dogs demonstrated a significant decrease in maximal respiration when treated with rapa. In opposition to rapa treatments, met significantly decreased basal OCR levels in cells from small and large breed puppies. Our data suggest that rapa treatments may be metabolically beneficial to dogs when started early in life and more beneficial in larger breeds.
... For example, body size and lifespan have been positively correlated interspecifically across mammalian species (Jimenez 2018). However, with body sizes ranging from the 2 kg Chihuahua to the 90 kg Great Dane, domestic dogs show the opposite association where smaller breeds of dogs tend to live significantly longer than larger breeds (Deeb and Wolf 1994;Patronek et al. 1997;Michell 1999;Jimenez 2016; it should be noted that other species of mammals, such as horses, can also demonstrate this pattern between longevity and body mass). On the other hand, wild canids do not demonstrate the same whole-animal traits as their domesticated counterparts. ...
Synopsis
Across Mammalia, body size and lifespan are positively correlated. However, in domestic dogs, the opposite is true: small dogs have longer lives compared with large dogs. Here, I present literature-based data on life-history traits that may affect dog lifespan, including adaptations at the whole-organism, and organ-level. Then, I compare those same traits to wild canids. Because oxidative stress is a byproduct of aerobic metabolism, I also present data on oxidative stress in dogs that suggests that small breed dogs accumulate significantly more circulating lipid peroxidation damage compared with large breed dogs, in opposition to lifespan predictions. Further, wild canids have increased antioxidant concentrations compared with domestic dogs, which may aid in explaining why wild canids have longer lifespans than similar-sized domestic dogs. At the cellular level, I describe mechanisms that differ across size classes of dogs, including increases in aerobic metabolism with age, and increases in glycolytic metabolic rates in large breed dogs across their lifespan. To address potential interventions to extend lifespan in domestic dogs, I describe experimental alterations to cellular architecture to test the “membrane pacemaker” hypotheses of metabolism and aging. This hypothesis suggests that increased lipid unsaturation and polyunsaturated fatty acids in cell membranes can increase cellular metabolic rates and oxidative damage, leading to potential decreased longevity. I also discuss cellular metabolic changes of primary fibroblast cells isolated from domestic dogs as they are treated with commercially available drugs that are linked to lifespan and health span expansion.
... In this group, body sizes range from the 2-kg Chihuahua to the 90-kg Great Dane (23). Smaller dogs tend to live significantly longer than larger dogs across all breeds (9,23,30,35), and they have also been positively correlated to lower cancer risks (30), with demonstrated lower prevalence of age-related diseases such as cataracts (47). A single insulin growth factor-1 (IGF1) haplotype seems to substantially con-tribute to size variation in dogs (42), and serum IGF-1 is reduced in small dogs relative to concentrations in large breeds, providing a potential link to their longer lives (12). ...
Canids are a morphological and physiological diverse group of animals, with the most diversity found within one species, the domestic dog. Underlying the observed morphological differences must be cellular-level differences that could lead to elucidating aging rates and lifespan disparities between wild and domestic canids. Furthermore, small breed dogs live significantly longer lives than large breed dogs while having higher mass-specific metabolic rates and faster growth rates. At the cell level, a clear mechanism underlying whole-animal traits has not been fully elucidated, though, oxidative stress has been implicated as a potential culprit of the disparate lifespans of domestic dogs. We used separated blood from known age domestic dogs and wild canids, and measured several oxidative stress variables: total antioxidant capacity (TAC), lipid damage, and enzymatic activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). We used phylogenetically corrected analysis and non-phylogenetically corrected analysis. We found that lipid damage increases with age in domestic dogs; whereas TAC increases with age and TAC and GPx activity increase as a function of age/Maximum lifespan (MLSP) in wild canids, which may partly explain longer potential lifespans in wolves. As body mass increases TAC and GPx activity increases in wild canids, but not domestic dogs, highlighting that artificial selection may have decreased antioxidant capacity in domestic dogs. We found that small breed dogs have significantly higher circulating lipid damage compared with large breed dogs, concomitant to their high mass-specific metabolism and higher growth rates, but in opposition to their long lifespans.
Objective:
In people, the dose of propofol (DOP) required for procedural sedation and anesthesia decreases significantly with age. The objective of this study was to determine if the DOP required to perform endotracheal intubation decreases with age in dogs.
Study design:
Retrospective case series.
Animals:
1397 dogs.
Methods:
Data from dogs anesthetized at referral center (2017-2020) were analyzed with three multivariate linear regression models with backward elimination using a combination of either absolute age, physiologic age, or life expectancy (ratio between age at the time of anesthetic event and expected age of death for each breed obtained from previous literature) as well as other factors as independent variables, and DOP as the dependent variable. The DOP for each quartile of life expectancy (<25%, 25-50%, 50-75%, 75-100%, >100%) was compared using one-way ANOVA. Significance was set at alpha = 0.025.
Results:
Mean age was 7.2 ± 4.1 years, life expectancy 59.8 ± 33%, weight 19 ± 14 kg, and DOP 3.76 ± 1.8 mg kg-1. Among age models, only life expectancy was a predictor of DOP (-0.37 mg kg-1; P = 0.013) but of minimal clinical importance. The DOP by life age expectancy quartile was 3.9 ± 2.3, 3.8 ± 1.8, 3.6 ± 1.8, 3.7 ± 1.7, and 3.4 ± 1.6 mg kg-1, respectively (P = 0.20). Yorkshire Terrier, Chihuahua, Maltese, mixed breed dogs under 10 kg, and Shih Tzu required higher DOP. Status of neutered male, ASA E, and Boxer, Labrador and Golden Retriever breeds decreased DOP, along with certain premedication drugs.
Conclusions and clinical relevance:
In contrast to what is observed in people, an age cut-off predictive of DOP does not exist. Percentage of elapsed life expectancy along with other factors such as breed, premedication drug, emergency procedure, and reproductive status significantly alter DOP. In older dogs, the dose of propofol can be adjusted based on their elapsed life expectancy.
Com o objetivo de determinar as principais causas de morte em cães e gatos, foram analisadas informações correspondentes às fichas clínicas de cães e gatos provenientes de um hospital veterinário universitário entre julho de 2005 e julho de 2009. Durante o período estudado foram atendidos 2243 casos novos, sendo 2075 cães e 168 gatos. Em cães, o percentual de óbito foi de 10,6% (220/2075) e em gatos, 8,92% (15/168). A idade média quando do óbito em cães e gatos foi de 59,97 e 82,79 meses, respectivamente. Em cães, as principais causas de morte e razões para eutanásia foram distúrbios infecciosos ou parasitários, distúrbios causados por agentes físicos e neoplasias. Exceto pela idade, as demais características de resenha não influenciaram a expectativa de vida ou a causa de morte em cães. Em gatos, distúrbios provocados por agentes físicos e distúrbios urinários foram os principais motivos que resultaram na morte do animal. Os resultados observados identificam a necessidade de medidas profiláticas que possibilitarão maior expectativa de vida e, consequentemente, alteração na frequência das principais causas de morte e razões para eutanásia em cães e gatos.
Canine hyperadrenocorticism is a common endocrine disorder caused by chronic secretion of glucocorticoid, often associated with hypercoagulability and secondary thrombosis. The thrombin generation assay (TGA) evaluates hemostasis globally by measuring endogenous thrombin potential. We aimed to determine whether TGA is suitable for assessing hypercoagulability in dogs with endogenous HAC, and to correlate TGA with coagulation markers including fibrinogen, antithrombin (AT), D-dimer, prothrombin time (PT) and activated partial thromboplastin time (aPTT), and with routine laboratory tests for elucidating prothrombotic mechanisms and evaluating their utility as hypercoagulability screening tests. Thrombin generation performed with high activator concentration showed significantly higher endogenous thrombin potential (ETP) (P = 0.0239) and peak thrombin (P = 0.0281) in Cushing patients. Fibrinogen (P = <0.0001) and AT (P = 0.0444) activities were significantly higher in the HAC group, while those of PT (P = 0.0046) and aPTT (P = 0.0002) were lower. Basal cortisol levels correlated positively with fibrinogen (r = 0.4503; P = 0.0355) and negatively with AT activity (r = -0.4580; P = 0.0280). Fibrinogen and hematocrit values were inversely correlated (r = -0.4853; P = 0.0076). Our study confirmed the presence of higher thrombin generation in dogs with HAC. However, TGA performed with lower activator concentrations was unsuitable for detecting hypercoagulability. Higher AT and fibrinogen levels and lower aPTT activity were identified in dogs with HAC relative to controls suggesting a potential role for the combined use of these assays when assessing hypercoagulability in canine hyperadrenocorticism.
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