Metabolomics of aging in primary fibroblasts from small and large breed dogs

Abstract

Among several animal groups (eutherian mammals, birds, reptiles) lifespan positively correlates with body mass over several orders of magnitude. Contradicting this pattern are domesticated dogs, with small dog breeds exhibiting significantly longer lifespans than large dog breeds. The underlying mechanisms of differing aging rates across body masses are unclear, but it is generally agreed that metabolism is a significant regulator of the aging process. Herein, we performed a targeted metabolomics analysis on primary fibroblasts isolated from small and large breed young and old dogs. Regardless of size, older dogs exhibited lower glutathione and ATP, consistent with a role for oxidative stress and bioenergetic decline in aging. Furthermore, several size-specific metabolic patterns were observed with aging, including: (i) An apparent defect in the lower half of glycolysis in large old dogs at the level of pyruvate kinase. (ii) Increased glutamine anaplerosis into the TCA cycle in large old dogs. (iii) A potential defect in co-enzyme A biosynthesis in large old dogs. (iv) Low nucleotide levels in small young dogs that corrected with age. (v) An age dependent increase in carnitine in small dogs that was absent in large dogs. Overall, these data support the hypothesis that alterations in metabolism may underlie the different lifespans of small versus large breed dogs, and further work in this area may afford potential therapeutic strategies to improve the lifespan of large dogs.

Accelerating the clock: Interconnected speedup of energetic and molecular dynamics during aging in cultured human cells

“…Overall, the speedup of isolated human fibroblasts mimics the cross-species relationships of size, MR, and lifespan. Our findings are further in line with the relationship between size and metabolism of fibroblasts from different sized dogs (Brookes & Jimenez, 2021; Jimenez et al, 2018). Moreover, amongst invertebrates, smaller organisms with higher metabolic rates have been documented to have slowed time perception (perceive more units of time each second) (Healy et al, 2013).…”

Age, breed, sex and diet influence serum metabolite profiles of 2000 pet dogs

“…However, as our results show quite large and systematic differences between the measurand levels of heavy-structured and lean breeds, it is possible that the actual body size and body condition could also influence metabolism. Metabolic differences between small and large-sized dogs have been described earlier [67,68], but breed effects have not been controlled in the studies. Notwithstanding, further research regarding the effects of actual height, weight and body condition of the study participants is warranted.…”