How does evolutionary evaluation illuminate body size among canids?

In this review, we examine mammalian body size as it reflects life history and genomic composition, with a primary focus on canids and the domestication of the gray wolf. The range of variation in body size is greater among Carnivora than any other terrestrial order. In the Canidae, this range is some 2 orders of magnitude. Macroevolutionary patterns (eg, Bergmann's rule and Cope's rule) that have been proposed in the past often fail to comport with modern studies on this aspect of carnivoran evolution. Clades often begin with small to medium size (mesocarnivorans) and diversify mostly in a right-skewed (larger) direction. The observed variation in body size reflects phenotypic plasticity in response to life history. As with many Mammalia, historically high gene flow (hybridization and introgression) among canid lineages has been a crucial source of genomic variation (nuclear and mitochondrial), yielding the potential for high plasticity of phenotypes such as body size. In addition, epigenetic marks connect genetic expression with environmental conditions in the manifested phenotypes. Among Mammalia generally, a larger size is associated with a longer life span, reflecting the foregoing genomic composition and environmental influences over a long geological time. However, the larger modern domestic dog breeds trend toward shorter life spans. The latter appears to reflect genetically mediated phenotypes that emerged secondary to domestication but nonetheless against a background of broadly and deeply conserved developmental and physiological patterns and body plans.

Metabolic phenotype modulation by caloric restriction in a lifelong dog study.

Modeling aging and age-related pathologies presents a substantial analytical challenge given the complexity of gene-environment influences and interactions operating on an individual. A top-down systems approach is used to model the effects of lifelong caloric restriction, which is known to extend life span in several animal models. The metabolic phenotypes of caloric-restricted (CR; n = 24) and pair-housed control-fed (CF; n = 24) Labrador Retriever dogs were investigated by use of orthogonal projection to latent structures discriminant analysis (OPLS-DA) to model both generic and age-specific responses to caloric restriction from the ¹H NMR blood serum profiles of young and older dogs. Three aging metabolic phenotypes were resolved: (i) an aging metabolic phenotype independent of diet, characterized by high levels of glutamine, creatinine, methylamine, dimethylamine, trimethylamine N-oxide, and glycerophosphocholine and decreasing levels of glycine, aspartate, creatine and citrate indicative of metabolic changes associated largely with muscle mass; (ii) an aging metabolic phenotype specific to CR dogs that consisted of relatively lower levels of glucose, acetate, choline, and tyrosine and relatively higher serum levels of phosphocholine with increased age in the CR population; (iii) an aging metabolic phenotype specific to CF dogs including lower levels of liproprotein fatty acyl groups and allantoin and relatively higher levels of formate with increased age in the CF population. There was no diet metabotype that consistently differentiated the CF and CR dogs irrespective of age. Glucose consistently discriminated between feeding regimes in dogs (≥312 weeks), being relatively lower in the CR group. However, it was observed that creatine and amino acids (valine, leucine, isoleucine, lysine, and phenylalanine) were lower in the CR dogs (<312 weeks), suggestive of differences in energy source utilization. ¹H NMR spectroscopic analysis of longitudinal serum profiles enabled an unbiased evaluation of the metabolic markers modulated by a lifetime of caloric restriction and showed differences in the metabolic phenotype of aging due to caloric restriction, which contributes to longevity studies in caloric-restricted animals. Furthermore, OPLS-DA provided a framework such that significant metabolites relating to life extension could be differentiated and integrated with aging processes.

Chronology of hip dysplasia development in a cohort of 48 Labrador retrievers followed for life.

OBJECTIVE: To determine the chronology of radiographic signs of canine hip dysplasia (CHD), specifically joint laxity and secondary osteoarthritis (OA). STUDY DESIGN: Longitudinal cohort study. ANIMALS: Paired littermates, 48 Labrador retrievers. METHODS: Conventional, ventrodorsal, hip-extended (HE) radiographs were evaluated yearly for CHD according to the subjective criteria of the Orthopedic Foundation for Animals (OFA). PennHIP screening was performed at 2 years of age to assess joint laxity by distraction index (DI). Histopathologic evaluation of coxofemoral joints was performed at the dogs' natural end of life. RESULTS: Coxofemoral subluxation, as identified on the HE radiograph occurred by 2 years of age and not thereafter. Accuracy of OFA-criteria scoring was poor: 55% of dogs scored "normal" at 2 years of age became radiographically dysplastic by the end of life (45% negative predictive value, NPV); 92% of the dogs scored as normal at 2 years of age had histopathologic OA of CHD (8% NPV). The DI predicted all 48 dogs to be susceptible to OA of CHD and 98% had radiographic or histopathologic OA by the end of life. CONCLUSION: OFA-criteria score was profoundly influenced by environmental factors, such as diet restriction and age, reducing its value as a selection criterion. DI measurements were not influenced by dietary treatment suggesting higher trait heritability.

The nature of coxofemoral joint pathology across family Canidae.

We evaluated coxofemoral joints from museum specimens of: Vulpes lagopus; Vulpes vulpes; Vulpes velox; Nyctereutes procyonoides; Urocyon cinereoargenteus; Aenocyon [Canis] dirus; Canis latrans; Canis lupus lupus; Canis lupus familiaris; C. l. familiaris × latrans; and Canis dingo. Acetabular components included: fossa; articular surface; medial and lateral articular margins; and periarticular surfaces. Acetabular components variably revealed: osteophyte-like features; varying appearance of articular margin rims (especially contour changes); rough bone surfaces (especially fossa and articular surface); and surface wear. Proximal femoral components included: articular surface; articular margin; periarticular surfaces; and joint capsule attachment. Femoral components variably revealed: rough bone surface; bone loss; articular margin osteophyte-like features; caudal post-developmental mineralized prominence; and enthesophytes along the joint capsule attachment. Non-metric multidimensional scaling was used to analyze right-left asymmetric relationships between observed traits, across taxa. Significantly different acetabular trait asymmetry involved only C. latrans-C. l. familiaris; V. vulpes-N. procyonoides, and U. cinereoargenteus-N. procyonoides. There were no significant lateralized differences in proximal femoral traits involving modern canids, ancient and modern C. l. familiaris, or modern vulpines. Thus, the observations were strongly bilateral. We hypothesized high similarity of traits across taxa. The data confirm the hypothesis and strongly suggest broad and deep morphological and mechanistic conservation that almost certainly pre-existed (at least) all modern canids. Further zoological studies are needed to evaluate phylogenic implications in greater detail.

Developmental features of the canid proximocaudal femur.

We continued direct morphological studies of the canid coxofemoral joint, considering early-life spatial relationships around the locus of the proximocaudal joint capsule insertion. Our primary goal was to elucidate the postnatal developmental gross anatomy of the proximocaudal femur, among juveniles across Canidae. From an original database of 267 independent (museum) specimens from 11 canid taxa and 1 hybrid taxon, we identified 29 ancient or modern candidate juvenile specimens (nine taxa and one hybrid taxon). Based on optimal ability to recognize landmarks, the best photographic data were categorized into five groups of four each (n = 20). The data groups approximated early juvenile, early-mid juvenile, mid-juvenile, mid-late juvenile; and young adult stages. In this descriptive photographic essay, we demonstrate the developmental spatial proximity among (a) the dorsal meeting of the respective lateral and medial extensions from the growth centers of the femoral head and greater trochanter; (b) the caudodorsal aspect of the coxofemoral joint capsule attachment; (c) a segment of the proximocaudal femoral shaft physis; and (d) an eventual associated mineralized prominence. The latter occurs frequently but not universally, suggesting natural population variability across taxa. Across taxa and juvenile age categories, the morphology thus supports developmental conservation among ancient and modern Canidae. The biomechanical and biological cause-effect implications are not yet clear. For zoological purposes, we apply the term postdevelopmental mineralized prominence to the residual caudolateral surface feature. We extend the original anatomical work of Morgan in zoological and phylogenic arenas, using direct observation of cleared skeletal specimens.

Morphology-based diagnostics of "protodogs." A commentary to Galeta et al., 2021, Anatomical Record, 304, 42-62, doi: 10.1002/ar.24500.

In a recent article in this journal, Galeta et al., (2020) discussed eight Pleistocene "protodogs" and seven Pleistocene wolves. Those "protodogs" had been diagnosed in earlier publications, based on skull morphology. We re-examined the Galeta et al. paper to offer comments on their observed outcomes, and the conclusion of presumed domestication. Of seven metrics that the authors used, five differed statistically between their two groups. However, from more elaborate studies, some of those same metrics had been rejected previously as not valid species-distinguishing traits. In this respect, we do accept cranium size and wider palate as species-distinguishing metrics. The physical size of their specimens was much larger than other archaeological specimens that have been accepted as dogs. Additionally, their sample size was small, compared to the number of available specimens, as shown from previous publications by the same group. Thus, we considered statistical differences that were found between groups in their study, and assessed whether the outcomes could have resulted from natural morphological variation. We examined a group of 73 dire wolves ((Aenocyon [Canis] dirus; Perri et al., 2021), using the same methods as used by Galeta et al., (2020). We could segregate two distinct morphological groups in our study, one having outcomes that were identical to the "protodogs" in Galeta et al. (2020). For the specimens of extinct dire wolves to segregate in the same way as the subjects from Galeta et al. indicates that natural variation probably was the driver of their observed outcomes, domestication being an unlikely assumption.

Osteoarthritis from evolutionary and mechanistic perspectives.

Developmental osteogenesis and the pathologies associated with tissues that normally are mineralized are active areas of research. All of the basic cell types of skeletal tissue evolved in early aquatic vertebrates. Their characteristics, transcription factors, and signaling pathways have been conserved, even as they adapted to the challenge imposed by gravity in the transition to terrestrial existence. The response to excess mechanical stress (among other factors) can be expressed in the pathologic phenotype described as osteoarthritis (OA). OA is mediated by epigenetic modification of the same conserved developmental gene networks, rather than by gene mutations or new chemical signaling pathways. Thus, these responses have their evolutionary roots in morphogenesis. Epigenetic channeling and heterochrony, orchestrated primarily by microRNAs, maintain the sequence of these responses, while allowing variation in their timing that depends at least partly on the life history of the individual.

A wolf from Gravettian site Pavlov I, Czech Republic: Approach to skull pathology.

OBJECTIVE: Describe pathological features on internal and external aspects of the skull of an ancient grey wolf. MATERIALS: Wolf remains that were found at the southwestern settlement Area A of Gravettian site Pavlov I. METHODS: Visual observation and description; microcomputed tomography; porosity and fragmentation indices for internal and external skull features; histological section of the fourth upper premolar tooth. RESULTS: Dorsally, the sagittal crest revealed bone healing and remodeling. The sagittal lesion differential diagnosis was blunt trauma with or without fracture. Ventrally, otic region pathology included severe proliferation and lysis (osteomyelitis). The pathology was not resolvable among differential (microbial) causes of osteomyelitis, although other potential etiologies were ruled out. CONCLUSIONS: Probable first report of otic region osteomyelitis in an ancient grey wolf. SIGNIFICANCE: The proximity of the wolf remains to human-related findings, and presence of red ochre and shells, suggest human involvement in the burial. LIMITATIONS: This is a single specimen with differential diagnoses that were not resolvable to a single definitive diagnosis. SUGGESTIONS FOR FURTHER RESEARCH: Further investigation of the possible anthropological significance of the burial circumstances.

Un-united medial epicondyle of the humerus: radiographic prevalence and association with elbow osteoarthritis in a cohort of labrador retrievers.

OBJECTIVE: To longitudinally characterize the radiographic appearance of un-united medial epicondyle (UME) of the humerus, evaluate UME association with osteoarthritis (OA) and consider its relevance to the elbow dysplasia complex. STUDY DESIGN: Longitudinal cohort study. ANIMALS: Labrador retrievers (n=48) from 7 litters. METHODS: Forty-eight same-sex littermates were paired for this lifetime feeding study. One of each pair was control-fed; the pair mate was fed 25% less than the control each day. Elbows of 46 surviving dogs were radiographed at ages 6 and 8 years, and/or at end-of-life (EOL). Elbow histopathology was done EOL, although UME lesions were not evaluated histologically. RESULTS: Seven dogs (15%) had UME, representing 5 litters; 4 were control-fed, 3 diet-restricted. Six (86%) dogs had unilateral lesions; 1 was bilateral. UME was evident on craniocaudal (CrCd) radiographic projections by 8 years in all dogs. UME was detected in only 1 elbow by mediolateral radiographic projection. Elbow OA frequency in UME affected dogs was not significantly different from the remaining study population. Histopathologic lesions were bilateral in dogs with unilateral UME. CONCLUSIONS: UME may be more common than previously thought. Most cases were unilateral and diet restriction had no effect on frequency. The CrCd view was critical for diagnosis. Elbow OA was not directly associated with UME. CLINICAL RELEVANCE: Infrequent diagnosis of UME could result from infrequent radiography and use of only the flexed lateral radiographic projection required by the Orthopedic Foundation for Animals for elbow screening. Like hip evaluations, screening for UME should be continued for life, until genetics are better understood. Lack of association between UME and elbow OA suggests that UME is not likely a component of elbow dysplasia.

A longitudinal study of the influence of lifetime food restriction on development of osteoarthritis in the canine elbow.

OBJECTIVE: To report the effects of age and lifetime calorie restriction on development and progression of osteoarthritis (OA) in elbow joints of Labrador retrievers. STUDY DESIGN: Longitudinal cohort study. ANIMALS: Labrador retriever dogs (n=48). METHODS: Puppies from 7 litters were allotted to 2 groups of 24 dogs each. Diet-restricted (DR) dogs received 25% fewer calories than control-fed (CF) pair mates. Elbow radiographs were taken at 6 and 8 years of age and end of life (EOL). Gross and histopathologic evaluations for OA occurred at EOL. RESULTS: There was no statistical difference in radiographic OA frequency between groups at any of the time points. Radiographic OA severity was greater for CF dogs at 6 years only (P<.05). There was no significant difference between feeding groups for histopathologic prevalence or severity of OA. Similarly, there were no differences in gross OA lesions between the groups (P>.05). Fragmented medial coronoid process, un-united anconeal process, and osteochondrosis were not present in any elbow. CONCLUSION: No differences in prevalence or severity of radiographic and histopathologic elbow OA were found between feeding groups. Diet restriction resulted in a 1.8-year extension in median lifespan but no additional incremental worsening of elbow disease. Evaluation at time points <6 years may have revealed larger differences in OA prevalence and severity between the dietary groups. CLINICAL RELEVANCE: These findings support calorie restriction as a clinical tool to slow progression of elbow OA.

Features of the Femoral Proximocaudal Joint Capsule Insertion Among Canids.

This observational study was conducted to evaluate the anatomic relationship between the proximocaudal femoral joint capsule insertion and the femoral caudolateral curvilinear osteophyte (CCO), across ancient and modern domestic and non-domestic canids. Museum specimens of proximal femora were screened for presence of remnant enthesophytes of the caudal joint capsule insertion (first inclusion criterion) and then for the CCO (second inclusion criterion). The initially screened population included 267 dry bone specimens: Six Canis species, hybrid coyote × domestic dog, and five vulpines (three Vulpes species, one Urocyon, and one Nyctereutes). Proximocaudal joint capsule insertion remnant enthesophytes were limiting at n = 19 specimens: Seven ancient domestic dogs, four modern coyotes, two ancient coyotes, two modern hybrid coyote × dog, two modern red foxes, and two modern raccoon dogs. The joint capsule enthesophytes are associated with inflammation, but are observed far less frequently than the CCO. The CCO is seen radiographically but is visible more frequently by direct inspection. The primary inclusion criterion necessarily was a visible caudal joint capsule insertion; spatial relationships of the CCO can be assigned with confidence only when a capsule insertion line can be recognized clearly. We demonstrate that the anatomic CCO associates with the joint capsule insertion being nonspecific and species-independent. A joint capsule insertion-CCO spatial relationship across species is an important new observation, strongly indicating that both are pathological features. Our data indicate need for new research to characterize the canid coxofemoral joint and its overt and incipient pathology in a phylogenetic context. Anat Rec, 302:2164-2170, 2019. © 2019 American Association for Anatomy.

A Long-Term Lens: Cumulative Impacts of Free-Roaming Cat Management Strategy and Intensity on Preventable Cat Mortalities.

This study used a previously developed stochastic simulation model (1) to estimate the impact of different management actions on free-roaming kitten and cat mortality over a 10-year period. These longer-term cumulative impacts have not been systematically examined to date. We examined seven management scenarios, including: (1) taking no action, (2) low-intensity removal, (3) high-intensity removal, (4) low-intensity episodic culling, (5) high-intensity episodic culling, (6) low-intensity trap-neuter-return (TNR), and (7) high-intensity TNR. For each scenario we tracked within the model the number of kittens born, the number of kittens surviving to adulthood, and the number of adults removed using lethal control over the entire 10-year simulation. We further defined all kitten deaths and lethal removal of adults as "preventable" deaths because they could potentially be reduced by certain management actions. Our simulation results suggested that the cumulative number of preventable deaths over 10 years for an initial population of 50 cats is highest for a "no-action" scenario, estimated at 1,000 deaths. It is lowest for a high-intensity TNR scenario, estimated at 32 deaths, a 31-fold difference. For all management scenarios tested, including removal and culling, the model predicted fewer preventable deaths than for a no-action scenario. For all management scenarios, the model predicted that the higher-intensity option (defined in terms of the proportion of animals sterilized or removed within a given time period) would result in fewer preventable deaths over time than the lower-intensity option. Based on these findings, we conclude that management intensity is important not only to reduce populations more quickly, but also to minimize the number of preventable deaths that occur over time. Accordingly, the lessons for the animal welfare community are both encouraging and cautionary. With sufficient intensity, management by TNR offers significant advantages in terms of combined lifesaving and population size reduction. At lower intensity levels, these advantages are greatly reduced or eliminated. We recommend that those who seek to minimize suffering and maximize lifesaving for free-roaming cats attempt to balance prospective goals (i.e., saving lives tomorrow) with proximate goals (i.e., saving lives today), and recognize that thoughtful choice of management strategies can ensure that both of these complementary goals are achieved.

Self-modeling curve resolution recovery of temporal metabolite signal modulation in NMR spectroscopic data sets: application to a life-long caloric restriction study in dogs.

A novel model-free statistical approach (self modeling curve resolution, SMCR) has been applied to recover biochemical information from complex overlapping signals in (1)H NMR spectra of blood serum in a long-term study of caloric restriction (CR) in the dog (n = 24 control fed (CF) and n = 24 CR animals). A new statistical spectroscopic construct, the spectrotype, is proposed which is a spectroscopic subset description or component of a metabolic phenotype. Characterization of the (1)H NMR profiles according to their evolutionary contribution of each spectrotype gives clues to the kinetics of the macro-biochemical response profiles and the identity of the underlying biochemical constituents, governing the evolutionary global response to an intervention. This information can be used to monitor and predict the end point of the biological process and to identify the mechanisms responsible for those changes. Here a SMCR strategy together with a pattern recognition method, principal component analysis (PCA) was used to resolve sets of spectrotypes, without a priori information. From the (1)H NMR evolutionary response profiles, two spectrotypes were identified and resolved; spectrotype 1 dominated by lipids featuring contributions from phosphatidylcholine, lipoprotein lipid fatty acyl groups from triglycerides, phospholipids, and cholesteryl esters plus total cholesterol (i.e., both esterified and unesterified); spectrotype 2 comprising glucose signals and a poorly resolved envelope of albumin and N-acetylated glycoprotein resonances. The relative contributions of these spectrotypes in each sample were calculated. For both caloric restricted (CR) and control fed (CF) dogs between ages 1 and 9 years, the contribution of spectrotype 2 > spectrotype 1, whereas for dogs aged between 9 and 12 years spectrotype 1 > spectrotype 2. Therefore, SMCR analysis pinpointed ages where nutrition and aging metabolic changes became significant within serum samples as well as providing the individual longitudinal contribution profiles associated with each spectrotype, which could potentially be used as part of a strategy to monitor and predict longevity and morbidity in populations. Hence SMCR is a useful addition to the chemometric "toolbox" for metabolic analysis and should have diverse applications within other biomedical conditions characterized by subtle time-dependent changes.

Automated SPE-RP-HPLC fractionation of biofluids combined to off-line NMR spectroscopy for biomarker identification in metabonomics.

NMR-based metabonomics is a valuable and straightforward approach to measuring hundreds of metabolites in complex biofluids. However, metabolite identification is sometimes limited by overlapped signals in NMR spectra. We describe a new methodology using an automated hyphenation of solid phase extraction (SPE) with RP-HPLC combined to NMR spectroscopy, which allowed identification of 72 metabolites of various molecular classes in human urine. This methodology was also successfully applied to the fractionation of a cat urine sample to aid identification of aromatic compounds and felinine. The SPE-RP-HPLC method appears to be a reliable tool to support biomarker discovery in metabonomic studies.

Exploring human/animal intersections: converging lines of evidence in comparative models of aging.

At a symposium convened on March 8, 2007 by the Institute on Aging at the University of Pennsylvania, researchers from the University's Schools of Medicine and Veterinary Medicine explored the convergence of aging research emerging from the two schools. Studies in human patients, animal models, and companion animals have revealed different but complementary aspects of the aging process, ranging from fundamental biologic aspects of aging to the treatment of age-related diseases, both experimentally and in clinical practice. Participants concluded that neither animal nor human research alone will provide answers to most questions about the aging process. Instead, an optimal translational research model supports a bidirectional flow of information from animal models to clinical research.

The effects of lifetime food restriction on the development of osteoarthritis in the canine shoulder.

OBJECTIVE: To report effects of age and lifetime food restriction on development and progression of shoulder joint osteoarthritis (OA) in Labrador retriever dogs. STUDY DESIGN: Longitudinal life-span, cohort study. ANIMALS: Labrador retriever dogs (n=48). METHODS: Littermates were paired (gender, weight) to make 24 pairs of genetically similar dogs. Each diet-restricted (DR) pair-mate was fed daily 75% of the same diet consumed by its control-fed (CF) pair-mate for life. Shoulders were evaluated radiographically at years 6, 8, and end of life (EOL). At EOL shoulders were evaluated grossly and by histopathology for OA. RESULTS: Radiographic evidence of shoulder OA was identified in 78% of dogs. Severity of radiographic shoulder OA at 6 (P<.03) and 8 years (P<.02) was significantly lower among DR dogs compared with CF dogs. Pooled gross evaluation results revealed 40 of 46 dogs had cartilage erosion on the caudal aspect of the humeral head. By EOL, 91% of dogs had histopathologic changes consistent with OA. CONCLUSION: There was a high overall prevalence of radiographic, gross, and histologic OA among dogs. Substantial disparity was found between radiographic evidence of OA (at EOL) and characteristic changes visible by gross and histologic examination. CLINICAL RELEVANCE: Radiographic evaluation correlates poorly with severity of shoulder joint pathology. The benefits of DR on shoulder OA are consistent with the demonstrated effect of DR in delaying species- and strain-specific diseases of aging.

Influence of lifetime food restriction on physiological variables in Labrador retriever dogs.

Effects of lifetime food restriction on erythrocytes and numerous clinical chemistry, thyroid, parathyroid, and acid-base variables are reported from a paired-feeding study of 25% diet restriction in dogs. The 48 dogs were paired by gender and weaning weight within litter, and 1 dog in each pair was fed 25% less than its pair mate, from age 8 weeks until death. Erythrocyte and serum biochemistry profiles were evaluated by annual sampling intervals and longitudinally. Erythrocyte variables were slightly higher among control-fed dogs, a possible reflection of the need to support both higher body fat mass and lean mass that uses energy less efficiently. Among serum biochemistry variables, glucose and triglyceride were lower among diet-restricted dogs, while creatinine was slightly higher in the absence of renal disease or failure, over the life spans of the dogs. Glucose outcomes reflect improved glucose tolerance that has been demonstrated with diet restriction protocols in several species, while triglyceride data may reflect the difference in total body fat cells between feeding groups. Creatinine outcomes may reflect lean mass responses to diet restriction or more efficient function of the intracellular proteasome. Serum triiodothyronine levels were lower among diet-restricted dogs. Other clinical chemistry and thyroid variables, parathyroid variables, and acid-base variables were not strongly influenced by diet restriction but revealed age-related effects.

Evaluation of a circumferential femoral head osteophyte as an early indicator of osteoarthritis characteristic of canine hip dysplasia in dogs.

OBJECTIVE: To determine the relationship between a circumferential femoral head osteophyte (CFHO) and osteoarthritis characteristic of canine hip dysplasia, and to ascertain whether CFHO, like osteoarthritis, varies between diet-restricted and control-fed dogs. DESIGN: Longitudinal cohort study. ANIMALS: 48 Labrador Retrievers. PROCEDURES: Dogs were paired by size, sex, and litter and assigned to 1 of 2 equal groups at 2 months of age. The control-fed group was fed ad libitum, and the diet-restricted group was fed 25% less on a pairwise basis of the same diet for life. The dogs' hip joints were radiographed yearly for life. Each radiograph was evaluated for radiographic signs of osteoarthritis characteristic of hip dysplasia and for the presence and severity of a CFHO. RESULTS: 41 of the 48 (85.4%) dogs had a CFHO, which was detected at a median age of 5.4 years, and 33 of those 41 (80.5%) developed radiographic evidence of osteoarthritis. Nineteen (79.2%) dogs in the diet-restricted group and 22 (91.7%) in the control-fed group had a CFHO at a median age of 9 and 3 years, respectively. Of the dogs with a CFHO, 12 (63.2%) in the diet-restricted group and 20 (90.0%) in the control-fed group developed radiographic evidence of osteoarthritis characteristic of hip dysplasia at a median age of 11 and 6.5 years, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a relationship between the CFHO and subsequent development of radiographic signs of osteoarthritis. If a CFHO is present in Labrador Retrievers, it might be considered an early indicator of osteoarthritis.

Modulation of canine immunosenescence by life-long caloric restriction.

Caloric restriction (CR) has been shown to retard immunosenescence and to extend median and maximum life span in rodent species. Longitudinal effects of CR on the canine immune system are presented in this report. A group of 48 Labrador Retrievers, divided at weaning into weight- and sex-matched pairs, were maintained on a diet restriction protocol from age 8 weeks until death. Each restricted dog received 75% of the total food consumed by its control-fed pair mate. Immune parameters were monitored from 4 to 13 years. CR retarded age-related declines in both lymphoproliferative responses and absolute numbers of lymphocytes and the T, CD4, and CD8-cell subsets. In females, CR attenuated the age-related increase in T-cell percentages and marginally retarded the age-related increase in memory cell percentages. Age-related changes in B-cell percentages and numbers were augmented by CR. No direct effect of CR on phagocytic activity of PMN, antibody production or NK cell activity, was observed. Lower lymphoproliferative responses, lower numbers of lymphocytes, T, CD4 and CD8 cells, lower CD8 percentages and higher B-cell percentages were all found to be significantly associated with a decreased likelihood of survival in these dogs.

The aging feline kidney: a model mortality antagonist?

Traditional thinking views apparently non-programmed disruptions of aging, which medical science calls geriatric diseases, as separate from 'less harmful' morphological and physiological aging phenotypes that are more universally expected with passage of time (loss of skin elasticity, graying of hair coat, weight gain, increased sleep time, behavioral changes, etc). Late-life disease phenotypes, especially those involving chronic processes, frequently are complex and very energy-expensive. A non-programmed process of homeostatic disruption leading into a death trajectory seems inconsistent with energy intensive processes. That is, evolutionary mechanisms do not favor complex and prolonged energy investment in death. Taking a different view, the naturally occurring feline (Felis silvestris catus) renal model suggests that at least some diseases of late life represent only the point of failure in essentially survival-driven adaptive processes. In the feline renal model, individuals that succumbed to failure most frequently displayed progressive tubular deletion and peritubular interstitial fibrosis, but had longer mean life span than cats that died from other causes. Additionally, among cats that died from non-renal causes, those that had degrees of renal tubular deletion and peritubular interstitial fibrosis also had longer mean life span than those cats with no changes, even though causes of death differed minimally between these latter two groups. The data indicate that selective tubular deletion very frequently begins early in adult life, without a clear initiating phase or event. The observations support a hypothesis that this prolonged process may be intrinsic and protective prior to an ultimate point of failure. Moreover, given the genetic complexity and the interplay with associated risk factors, existing data also do not support the ideas that these changes are simple compensatory responses and that breed- or strain-based 'default' diseases are inevitable results of increasing individual longevity. Emerging molecular technology offers the future potential to further evaluate and refine these observations. At present, the existence of plastic and adaptive aging programming is suggested by these findings.