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Cellular energetics and mitochondrial uncoupling in canine aging.

Publication ,  Journal Article
Nicholatos, JW; Robinette, TM; Tata, SVP; Yordy, JD; Francisco, AB; Platov, M; Yeh, TK; Ilkayeva, OR; Huynh, FK; Dokukin, M; Volkov, D ...
Published in: Geroscience
April 2019

The first domesticated companion animal, the dog, is currently represented by over 190 unique breeds. Across these numerous breeds, dogs have exceptional variation in lifespan (inversely correlated with body size), presenting an opportunity to discover longevity-determining traits. We performed a genome-wide association study on 4169 canines representing 110 breeds and identified novel candidate regulators of longevity. Interestingly, known functions within the identified genes included control of coat phenotypes such as hair length, as well as mitochondrial properties, suggesting that thermoregulation and mitochondrial bioenergetics play a role in lifespan variation. Using primary dermal fibroblasts, we investigated mitochondrial properties of short-lived (large) and long-lived (small) dog breeds. We found that cells from long-lived breeds have more uncoupled mitochondria, less electron escape, greater respiration, and capacity for respiration. Moreover, our data suggest that long-lived breeds have higher rates of catabolism and β-oxidation, likely to meet elevated respiration and electron demand of their uncoupled mitochondria. Conversely, cells of short-lived (large) breeds may accumulate amino acids and fatty acid derivatives, which are likely used for biosynthesis and growth. We hypothesize that the uncoupled metabolic profile of long-lived breeds likely stems from their smaller size, reduced volume-to-surface area ratio, and therefore a greater need for thermogenesis. The uncoupled energetics of long-lived breeds lowers reactive oxygen species levels, promotes cellular stress tolerance, and may even prevent stiffening of the actin cytoskeleton. We propose that these cellular characteristics delay tissue dysfunction, disease, and death in long-lived dog breeds, contributing to canine aging diversity.

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Published In

Geroscience

DOI

EISSN

2509-2723

Publication Date

April 2019

Volume

41

Issue

2

Start / End Page

229 / 242

Location

Switzerland

Related Subject Headings

  • Species Specificity
  • Reactive Oxygen Species
  • Phenotype
  • Oxidative Stress
  • Mitochondria
  • Longevity
  • Genome-Wide Association Study
  • Fibroblasts
  • Energy Metabolism
  • Dogs
 

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Nicholatos, J. W., Robinette, T. M., Tata, S. V. P., Yordy, J. D., Francisco, A. B., Platov, M., … Libert, S. (2019). Cellular energetics and mitochondrial uncoupling in canine aging. Geroscience, 41(2), 229–242. https://doi.org/10.1007/s11357-019-00062-6
Nicholatos, Justin W., Timothy M. Robinette, Saurabh V. P. Tata, Jennifer D. Yordy, Adam B. Francisco, Michael Platov, Tiffany K. Yeh, et al. “Cellular energetics and mitochondrial uncoupling in canine aging.Geroscience 41, no. 2 (April 2019): 229–42. https://doi.org/10.1007/s11357-019-00062-6.
Nicholatos JW, Robinette TM, Tata SVP, Yordy JD, Francisco AB, Platov M, et al. Cellular energetics and mitochondrial uncoupling in canine aging. Geroscience. 2019 Apr;41(2):229–42.
Nicholatos, Justin W., et al. “Cellular energetics and mitochondrial uncoupling in canine aging.Geroscience, vol. 41, no. 2, Apr. 2019, pp. 229–42. Pubmed, doi:10.1007/s11357-019-00062-6.
Nicholatos JW, Robinette TM, Tata SVP, Yordy JD, Francisco AB, Platov M, Yeh TK, Ilkayeva OR, Huynh FK, Dokukin M, Volkov D, Weinstein MA, Boyko AR, Miller RA, Sokolov I, Hirschey MD, Libert S. Cellular energetics and mitochondrial uncoupling in canine aging. Geroscience. 2019 Apr;41(2):229–242.

Published In

Geroscience

DOI

EISSN

2509-2723

Publication Date

April 2019

Volume

41

Issue

2

Start / End Page

229 / 242

Location

Switzerland

Related Subject Headings

  • Species Specificity
  • Reactive Oxygen Species
  • Phenotype
  • Oxidative Stress
  • Mitochondria
  • Longevity
  • Genome-Wide Association Study
  • Fibroblasts
  • Energy Metabolism
  • Dogs