Dog Models of Aging

Ruple, Audrey; MacLean, Evan L.; Snyder‐Mackler, Noah; Creevy, Kate E.; Promislow, Daniel

doi:10.1146/annurev-animal-051021-080937

Cited by 22 publications

(9 citation statements)

References 145 publications

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“…This facilitates investigation of genetic variables relevant to differences in lifespan and age-related health outcomes. The extensive annotation of the canine genome further supports such investigation ( 19 ).…”

Section: Introductionmentioning

confidence: 72%

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Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience

McKenzie¹,

Chen²,

Gruen

et al. 2022

Front. Vet. Sci.

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Biological aging is the single most important risk factor for disease, disability, and ultimately death in geriatric dogs. The effects of aging in companion dogs also impose significant financial and psychological burdens on their human caregivers. The underlying physiologic processes of canine aging may be occult, or early signs of aging may be ignored because of the misconception that biological aging is natural and therefore inevitable. The ability to detect, quantify, and mitigate the deleterious processes of canine aging would greatly enhance veterinary preventative medicine and animal welfare. In this paper we propose a new conceptual framework for aging in dogs, the Canine Geriatric Syndrome (CGS). CGS consists of the multiple, interrelated physical, functional, behavioral, and metabolic changes that characterize canine aging as well as the resulting clinical manifestations, including frailty, diminished quality of life, and age-associated disease. We also identify potential key components of a CGS assessment tool, a clinical instrument that would enable veterinarians to diagnose CGS and would facilitate the development and testing of interventions to prolong healthspan and lifespan in dogs by directly targeting the biological mechanisms of aging. There are many gaps in our knowledge of the mechanisms and phenotype of aging in dogs that must be bridged before a CGS assessment tool can be deployed. The conceptual framework of CGS should facilitate identifying these gaps and should stimulate research to better characterize the processes and effects of aging in dogs and to identify the most promising preventative strategies to target these.

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Section: Introductionmentioning

confidence: 72%

“…This facilitates the collection of extensive data on health risk factors and outcomes in dogs, supporting real-world clinical research on aging mechanisms and interventions. Canine biology and the role of dogs in human society make dogs an excellent translational model for human aging ( 16 – 19 ).…”

Section: Introductionmentioning

confidence: 99%

Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience

McKenzie¹,

Chen²,

Gruen

et al. 2022

Front. Vet. Sci.

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“…However, in addition to resource-constraints and participant-burden concerns that limit the frequency and depth of measurements, following a cohort of humans over their lifespan requires multiple generations of scientists and faces challenges of ever-changing techniques and technology for sample collection and analysis. One complementary strategy is to conduct lifespan studies of shorter-lived animals 20,21 , although these too require substantial time, and may be limited in their translability to humans 22 . Here we present a further complementary strategy: a “lifespan” study of cultured fibroblasts.…”

Section: Background and Summarymentioning

confidence: 99%

A Multi-Omics Longitudinal Aging Dataset in Primary Human Fibroblasts with Mitochondrial Perturbations

Sturm

Monzel

Karan

et al. 2021

Preprint

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Aging is a process of progressive change. In order to develop biological models of aging, longitudinal datasets with high temporal resolution are needed. Here we report a multi-omic longitudinal dataset for cultured primary human fibroblasts measured across their replicative lifespans. Based on the accelerated nature of epigenetic aging in vitro, these longitudinal data are equivalent to ~40 years of follow-up sampling at a frequency of every ~3 years. Fibroblasts were sourced from both healthy donors (n=6) and individuals with lifespan-shortening mitochondrial disease (n=3). The dataset includes cytological (cell size, morphology), bioenergetic (energy expenditure, derived ATP synthesis rates), epigenetic (DNA methylation), gene expression (RNA sequencing), secreted proteins, mitochondrial DNA (mtDNA) copy number and mutations, cell-free DNA, telomere length, and whole-genome sequencing data. This dataset enables the bridging of mechanistic processes of aging as outlined by the “hallmarks of aging”, with the descriptive characterization of aging provided by epigenetic clocks and other metrics. Here we focus on bridging the gap for the hallmark mitochondrial metabolism. Our dataset includes measurement of healthy cells replicating through senescence without intervention, as well as cells subjected to over a dozen experimental manipulations targeting oxidative phosphorylation (OxPhos), glycolysis, and glucocorticoid signaling, among others. These experiments provide opportunities to test how cellular energetics affect the biology of cellular aging. All data are publicly available at our webtool: https://columbia-picard.shinyapps.io/shinyapp-Lifespan_Study/

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“…However, to the authors' knowledge, the effect of aging on postural control in dogs has not yet been elucidated. Dogs are a powerful model for the study of aging for several reasons [15]. First of all, they are considered family members and share the living environment with their owners, which exposes them to the same stimuli and potential toxins [16].…”

Section: Introductionmentioning

confidence: 99%

Static posturography as a novel measure of the effects of aging on postural control in dogs

et al. 2022

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Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determine age-related changes in postural sway. Data were obtained from 40 healthy adult dogs (Group A) and 28 senior dogs (Group B) during seven trials (within one session of data collection) of quiet standing on a pressure sensitive walkway system. Velocity, acceleration, root mean square, 95% ellipse area, range and frequency revolve were recorded as measures of postural sway. In Group A, reliability was assessed with intraclass correlation, and the effect of morphometric variables was evaluated using linear regression. By means of stepwise linear regression we determined that root mean square overall and acceleration in the craniocaudal direction were the best variables able to discriminate between Group A and Group B. The relationship between these two center-of-pressure (COP) measures and the dogs’ fractional lifespan was examined in both groups and the role of pain and proprioceptive deficits was evaluated in Group B. All measures except for frequency revolve showed good to excellent reliability. Weight, height and length were correlated with most of the measures. Fractional lifespan impacted postural control in Group B but not Group A. Joint pain and its interaction with proprioceptive deficits influence postural sway especially in the acceleration in the craniocaudal direction, while fractional lifespan was most important in the overall COP displacement. In conclusion, our study found that pressure sensitive walkway systems are a reliable tool to evaluate postural sway in dogs; and that postural sway is affected by morphometric parameters and increases with age and joint pain.

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Dog Models of Aging

Cited by 22 publications

References 145 publications

Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience

Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience

A Multi-Omics Longitudinal Aging Dataset in Primary Human Fibroblasts with Mitochondrial Perturbations

Static posturography as a novel measure of the effects of aging on postural control in dogs

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