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Intrinsic Mitochondrial Dynamics and Cytoskeletal Properties Underlie Aging Diversity in Dogs

17 Pages Posted: 6 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Justin W. Nicholatos

Justin W. Nicholatos

Cornell University - Department of Biomedical Sciences

Saurabh V.P. Tata

Cornell University - Department of Biomedical Sciences

Timothy M. Robinette

Cornell University - Department of Biomedical Sciences

Adam B. Francisco

Cornell University - Department of Biomedical Sciences

Michael Platov

Cornell University - Department of Biomedical Sciences

Jennifer D. Yordy

Cornell University - Department of Biomedical Sciences

Olga R. Ilkayeva

Duke University - Duke Molecular Physiology Institute; Duke University - Sarah W. Stedman Nutrition and Metabolism Center

Frank K. Huynh

Duke University - Duke Molecular Physiology Institute; Duke University - Sarah W. Stedman Nutrition and Metabolism Center

Maxim Dokukin

Tufts University - Department of Mechanical Engineering

Dmyro Volkov

Tufts University - Department of Mechanical Engineering

Michael Weinstein

Tufts University - Department of Biomedical Engineering

Adam R. Boyko

Cornell University - Department of Biomedical Sciences

Richard A. Miller

University of Michigan at Ann Arbor - Department of Pathology

Igor Sokolov

Tufts University - Department of Mechanical Engineering; Tufts University - Department of Biomedical Engineering

Matthew D. Hirschey

Duke University - Duke Molecular Physiology Institute; Duke University - Sarah W. Stedman Nutrition and Metabolism Center

Sergiy Libert

Cornell University - Department of Biomedical Sciences

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Abstract

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.

Suggested Citation

Nicholatos, Justin W. and Tata, Saurabh V.P. and Robinette, Timothy M. and Francisco, Adam B. and Platov, Michael and Yordy, Jennifer D. and Ilkayeva, Olga R. and Huynh, Frank K. and Dokukin, Maxim and Volkov, Dmyro and Weinstein, Michael and Boyko, Adam R. and Miller, Richard A. and Sokolov, Igor and Hirschey, Matthew D. and Libert, Sergiy, Intrinsic Mitochondrial Dynamics and Cytoskeletal Properties Underlie Aging Diversity in Dogs (2018). Available at SSRN: https://ssrn.com/abstract=3155620 or http://dx.doi.org/10.2139/ssrn.3155620
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Justin W. Nicholatos (Contact Author)

Cornell University - Department of Biomedical Sciences ( email )

NY
United States

Saurabh V.P. Tata

Cornell University - Department of Biomedical Sciences

NY
United States

Timothy M. Robinette

Cornell University - Department of Biomedical Sciences

NY
United States

Adam B. Francisco

Cornell University - Department of Biomedical Sciences

NY
United States

Michael Platov

Cornell University - Department of Biomedical Sciences

NY
United States

Jennifer D. Yordy

Cornell University - Department of Biomedical Sciences

NY
United States

Olga R. Ilkayeva

Duke University - Duke Molecular Physiology Institute

NC
United States

Duke University - Sarah W. Stedman Nutrition and Metabolism Center

NC
United States

Frank K. Huynh

Duke University - Duke Molecular Physiology Institute

NC
United States

Duke University - Sarah W. Stedman Nutrition and Metabolism Center

NC
United States

Maxim Dokukin

Tufts University - Department of Mechanical Engineering

Medford, MA
United States

Dmyro Volkov

Tufts University - Department of Mechanical Engineering

Medford, MA
United States

Michael Weinstein

Tufts University - Department of Biomedical Engineering

Medford, MA
United States

Adam R. Boyko

Cornell University - Department of Biomedical Sciences

NY
United States

Richard A. Miller

University of Michigan at Ann Arbor - Department of Pathology

Ann Arbor, MI 48109,
United States

Igor Sokolov

Tufts University - Department of Mechanical Engineering

Medford, MA
United States

Tufts University - Department of Biomedical Engineering

Medford, MA
United States

Matthew D. Hirschey

Duke University - Duke Molecular Physiology Institute

NC
United States

Duke University - Sarah W. Stedman Nutrition and Metabolism Center

NC
United States

Sergiy Libert

Cornell University - Department of Biomedical Sciences ( email )

NY
United States

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