Citation:

Pandya, J., M. Valdez, J. Royland, R. MacPhail, P. Sullivan, AND P. Kodavanti. Age- and Organ-specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats. Journal of Aging Research. Hindawi Publishing Corporation, New York, NY, 2020(ID7232614):1-11, (2020). https://doi.org/10.1155/2020/7232614

Impact/Purpose:

This study describes age-related changes in mitochondrial bioenergetics in various organs using Brown Norway rats. The multi-dimensional design of this study will provide valuable insight into changes in individual organ metabolic status in response to aging. These data on mitochondrial bioenergetics will serve as a basic platform for future evaluation of multiple chemical and non-chemical stressors that may differentially target energy metabolism with respect to organ and/or life stage. In addition, information gained in this study will aid in understanding environmental chemical induced sensitivity in subsets of population, an important aspect of community health related research.

Description:

Mitochondria play a central role in energy homeostasis, and act as regulatory check-points for downstream metabolic responses and cell senescence processes during an entire life-span. Acute or chronic environmental toxicant exposures have shown deleterious organ-specific human health issues at various life-stages. Since mitochondria are a prime target for ensuing cellular bioenergetics responses and senescence, it is essential to understand mitochondrial bioenergetics responses in different organs over multiple life-stages. Therefore, in the present study, we evaluated mitochondrial bioenergetic parameters in liver, lung, and heart and compared with our previously published results on brain in four diverse age groups (young: 1 month; adult: 4 months; middle-aged: 12 months; old-aged: 24 month) using the male Brown Norway rat as a model of aging (n=5 sample size / organ / age group). Real-time mitochondrial bioenergetic parameters (i.e. State III, State IV, State V) were measured using the Seahorse Extracellular Flux Analyzer. Additionally, mitochondrial enzymes pyruvate dehydrogenase complex (PDHC), Complex I, Complex II, and Complex IV activities were measured using Synergy HT based plate reader. Nearly in all parameters, a significant age- and organ-specific interactions were observed. We observed age-specific declines in State III (i.e. ATP synthesis) responses in both heart and lung, where opposite was observed in liver as age advances. Across the age, heart has highest enzyme activities than liver and lung. Interestingly, heart and liver mitochondrial bioenergetics rates and enzyme activities remains higher than lung, which specifies their higher metabolic capabilities than lung. Amongst all, bioenergetics rates and enzyme activities in lung remains lowest suggesting lung may display higher vulnerability and lower resilience to environmental toxicants during aging than other organs tested here. Overall, these age- and organ-specific findings may facilitate a more contextualized understanding of mitochondrial bioenergetic outcomes when considering the interactions of age-related sensitivities with exposure to chemical-stressors from the environment.

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