Author ORCID Identifier

https://orcid.org/0000-0002-3759-8347

Date Available

12-9-2021

Year of Publication

2021

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Agriculture, Food and Environment

Department/School/Program

Veterinary Science

First Advisor

Dr. Amanda A. Adams

Abstract

Senior horses (≥ 15 years) represent up to one-third of the global equine population, and the proportion of old horses (≥ 20 years) in the U.S. has been steadily increasing. Aging is associated with a loss of skeletal muscle mass in horses, and while age-related muscle loss is comparingly well characterized in humans, little is currently known concerning underlying mechanisms, adverse outcomes, or the prevalence of low muscle mass in senior horses. One factor proposed to play a role in the development of age-related muscle atrophy in humans is inflamm-aging, a low-grade inflammation that affects elderly people and that has also been demonstrated in horses; however, the relationship between inflamm-aging and muscle mass in horses is currently unclear. Besides the development of inflamm-aging, the equine immune system is known to undergo various additional changes with advancing age. Concerning alterations in immune cell function, however, most studies thus far have concentrated on the adaptive immune system, while the effect of aging on innate immune cells, such as monocytes, is less understood.

The overarching goals of this dissertation were therefore 1) to improve our understanding of low muscle mass in senior horses in terms of prevalence, risk factors and adverse outcomes using a survey, 2) to create a muscle atrophy scoring system for horses, 3) to determine associations between low-grade inflammation and muscle mass in horses, and 4) to characterize monocyte function in old horses.

To determine the prevalence, risk factors for, and consequences of low muscle mass in senior horses, a U.S. wide survey with owners of horses aged ≥ 15 years was conducted. Almost 3000 individuals provided data on their senior horse in which the prevalence of low muscle mass was found to be 17.2%. Risk factors for low muscle mass identified in multi-variable regression were advancing age, male sex (gelding), osteoarthritis of the leg joints, pituitary pars intermedia dysfunction (PPID) and primary use type. In two-thirds of the horses with low muscle mass, either the ability to work, and/or welfare related aspects were impaired based on the owners’ observations. This study further provided insights into the primary use (e.g., retired, semi-retired, pleasure riding or competition riding) and the exercise regimen of the surveyed horses.

To facilitate the study of muscle mass, a muscle atrophy scoring system (MASS) was developed and tested in 38 horses. The scoring system was based on visual assessment of muscle mass and muscle palpation, and the scale ranged from 1 (no atrophy; normal muscle mass) to 4 (severe atrophy). Inter-rater agreement results were in the good to excellent range for ratings of the back, neck, and hind regions, but were poor for the abdominal region. Muscle atrophy scores of the neck, back and hind region were higher in horse groups in which atrophy is commonly observed, i.e., older, and PPID-positive horses, suggesting that the MASS may be a reliable tool for muscle atrophy assessment in the neck, back and hind region of horses, especially senior horses.

Relationships between circulating pro- and anti-inflammatory markers and muscle mass indicators were explored in 22 healthy horses of varying age (2-31 years). Muscle atrophy scores, estimated fat-free mass, and serum creatinine levels were used as muscle mass indicators and no significant associations between these parameters and the inflammatory markers were found; although trends for a positive association between hind region muscle atrophy scores and two of the markers were identified.

Lastly, the effect of age on monocyte inflammatory and phagocytic function was studied. Monocyte E. coli phagocytosis capacity and pro-inflammatory cytokine gene expression responses to lipopolysaccharide (LPS) stimulation were compared between young (4-6 years of age) and old (> 20 years of age) horses, and the results suggest that monocyte phagocytosis capacity and the IL-1β (a pro-inflammatory cytokine) response to LPS may be altered by aging in horses.

The findings of this dissertation provide first insights into muscle atrophy outcomes, risk factors, as well as potential mechanisms underlying muscle atrophy in senior horses. In addition, the results of this dissertation add to our understanding of age-related changes in the immune system of the horse. The MASS developed in this dissertation might serve equine practitioners and horse owners in identifying and monitoring muscle atrophy in horses.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2021.446

Funding Information

Hughes Foundation- Research Assistantship for Alisa Herbst (2017-2021)

Funding of lab & projects:

Mars Equestrian (2017-2021)

Mars Petcare US Incorporated (2017-2021)

Mars Horsecare UK Limited (2017-2021)

Gluck Equine Research Center internal Lincoln Memorial University Summer Research Grant (2018 and 2019)

Richards Graduate Student Award (2020)

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