Cellular metabolism and oxidative stress as a possible determinant for longevity in small breed and large breed dogs.

Ana Gabriela Jimenez,William Cipolli,Josh Winward,Ursula Beattie,Feng Ling

doi:10.1371/journal.pone.0195832

Abstract

Among species, larger animals tend to live longer than smaller ones, however, the opposite seems to be true for dogs—smaller dogs tend to live significantly longer than larger dogs across all breeds. We were interested in the mechanism that may allow for small breeds to age more slowly compared with large breeds in the context of cellular metabolism and oxidative stress. Primary dermal fibroblasts from small and large breed dogs were grown in culture. We measured basal oxygen consumption (OCR), proton leak, and glycolysis using a Seahorse XF96 oxygen flux analyzer. Additionally, we measured rates of reactive species (RS) production, reduced glutathione (GSH) content, mitochondrial content, lipid peroxidation (LPO) damage and DNA (8-OHdg) damage. Our data suggests that as dogs of both size classes age, proton leak is significantly higher in older dogs, regardless of size class. We found that all aspects of glycolysis were significantly higher in larger breeds compared with smaller breeds. We found significant differences between age classes in GSH concentration, and a negative correlation between DNA damage in puppies and mean breed lifespan. Interestingly, RS production showed no differences across size and age class. Thus, large breed dogs may have higher glycolytic rates, and DNA damage, suggesting a potential mechanism for their decreased lifespan compared with small breed dogs.

Highlights

Aging is defined as a decrease in physiological function and fitness with age [1], which is progressive, endogenously derived, and irreversible for the organism
Small breed dogs included in our study had significantly longer lifespans of 13.76 ± 0.38 years compared with large breed old dogs that lived 10.99 ± 0.47 years (ANOVA: F = 21.12, p < 0.001)
Lactate dehydrogenase, the enzyme that catalyses the conversion of anaerobically produced lactate to pyruvic acid, increases with age in blood from aging Beagles [47], and urine lactate increases with age in Labradors [48], an indication that increases in glycolytic pathways with age have been previously described in the literature, neither of the above studies compared the concentration of this enzyme across breed sizes Taken together, our metabolic rate data may suggest that oxygen consumption increases with aging in dogs, while glycolysis decreases

Summary

Introduction

Aging is defined as a decrease in physiological function and fitness with age [1], which is progressive, endogenously derived, and irreversible for the organism. Due to accumulation of deleterious traits in its forward progress [2], every aspect of an organism’s phenotype is modified during aging [3]. Mitochondria become larger and less numerous, mitochondrial respiration activity decreases and damage to mitochondrial DNA increases [5]. Mitochondrial RS production increase during aging, often leading to parallel increases in amounts of oxidative damage [6].

Methods

Results

Conclusion