Intrinsic Mitochondrial Dynamics and Cytoskeletal Properties Underlie Aging Diversity in Dogs
17 Pages Posted: 6 Apr 2018 Sneak Peek Status: Review CompleteMore...
Among its many breeds, dogs exhibit exceptional variation in their rate of aging and average lifespan, which presents an opportunity to identify longevity-associated traits via comparative analysis. Using primary dermal fibroblasts, we investigated mitochondrial dynamics, bioenergetics, and biomechanical properties in short and long-lived dog breeds. We demonstrated that intrinsic cellular properties correlate with canine breed longevity and likely underlie their aging diversity. More specifically, cells from longer lived-breeds have higher mitochondrial uncoupling and more efficient respiration dynamics, which appears to mitigate reactive oxygen species and promote stress tolerance. We also showed that fibroblasts of long-lived dogs had a more flexible cytoskeleton than their short-lived counterparts, which may similarly help protect cellular function. The benefits of these cellular characteristics likely translate upwards to the whole organism, slowing the rate of aging in long-lived dogs. Overall, our data support the uncoupling to survive hypothesis, where higher uncoupling in smaller breeds promotes longevity. The closeness of dogs and humans genetically and environmentally make these results pertinent to human biology.
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