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

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.

6-Bromoindirubin-3′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver

“…The end product of lipid peroxidation, MDA, is measured to reflect the level of hepatic oxidative damage. Similar to the findings of previous studies (Jimenez et al., 2018), the aged mice exhibited lower levels of SOD and GSH than the young mice, whereas a marked increase in MDA was observed in the aged group, indicating that liver oxidative stress increases with increasing age. Studies also report that the production of pro-inflammatory cytokines, such as IL-6, is linked to the aging process (Kim et al., 2016).…”

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs

“…Lastly, the dogs in the control and study populations differed significantly in both weight and breed. While this difference could have contributed to the significant difference found in urine isoprostane concentrations between the 2 groups, the control group was heavier, and oxidative stress is greater in larger animals …”

Effect of salinity acclimation on osmoregulation, oxidative stress, and metabolic enzymes in the invasive Xenopus laevis

“…Alternatively, several studies have reported that significant increases in metabolic rate can trigger ROS and therefore activate antioxidant defenses (Cohen, Hau, & Wikelski, 2008). Other studies suggest a functional relationship between mass‐specific metabolic rates and oxidative state (Fletcher et al, 2013; Sabat et al, 2017, 2019), although this association continues to be a subject of active debate (Jimenez, 2018; Selman et al, 2012; Speakman & Garratt, 2014). In particular, Speakman and Garratt (2014) proposed that the notion that ROS production is linked to metabolism in a fixed proportion is incorrect.…”

“…In addition to the energetic costs associated with osmoregulatory responses, oxidative metabolism is also a costly biological process (Jimenez, 2018). The cellular oxidative metabolism generates reactive oxygen species (ROS), which can interact with macromolecules (e.g., lipids, proteins, and nucleic acids) ultimately leading to disruption of multiple cellular processes when ROS are produced in excess (oxidative stress status; Giraud‐Billoud et al, 2019; Monaghan, Metcalfe, & Torres, 2009, 2010; Selman, Blount, Nussey, & Speakman, 2012).…”