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Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons

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Abstract

Biological resilience, broadly defined as the ability to recover from an acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences are likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue, and subject level. To address this question, we established primary cells from aged male and female baboons between 13.3 and 17.8 years spanning across different tissues, tissue regions, and cell types including (1) fibroblasts from skin and from the heart separated into the left ventricle (LV), right ventricle (RV), left atrium (LA), and right atrium (RA); (2) astrocytes from the prefrontal cortex and hippocampus; and (3) hepatocytes. Primary cells were characterized by their cell surface markers and their cellular respiration was assessed with Seahorse XFe96. Cellular resilience was assessed by modifying a live-cell imaging approach; we previously reported that monitors proliferation of dividing cells following response and recovery to oxidative (50 µM-H2O2), metabolic (1 mM-glucose), and proteostasis (0.1 µM-thapsigargin) stress. We noted significant differences even among similar cell types that are dependent on tissue source and the diversity in cellular response is stressor-specific. For example, astrocytes had a higher oxygen consumption rate and exhibited greater resilience to oxidative stress (OS) than both fibroblasts and hepatocytes. RV and RA fibroblasts were less resilient to OS compared with LV and LA, respectively. Skin fibroblasts were less impacted by proteostasis stress compared to astrocytes and cardiac fibroblasts. Future studies will test the functional relationship of these outcomes to the age and developmental status of donors as potential predictive markers.

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The data presented in the work are available from the corresponding author upon request.

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Acknowledgements

The authors acknowledge the administrative and technical support of Karen Moore, Wenbo Qi, Benjamin Morr, Raechel Camones, and Jonathan Gelfond. We also acknowledge support from the SNPRC which is funded by P51 OD011133.

Funding

This research was funded in part by R01 AG057431, I01BX004167 (ABS), the San Antonio Nathan Shock Center (P30 AG 013319), and the Geriatric Research, Education and Clinical Center of the South Texas Veterans Health Care System. This material is the result of work supported with resources and the use of facilities at South Texas Veterans Health Care System, San Antonio, Texas. Baboons in this study were maintained under 1U19AG057758-01A1 (PWN, LAC).

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Authors and Affiliations

  1. Department of Molecular Medicine and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA

    Daniel A. Adekunbi & Adam B. Salmon

  2. Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA

    Hillary F. Huber

  3. Department of Animal Science, Texas Pregnancy and Life-Course Health Research Center, University of Wyoming, Laramie, WY, USA

    Cun Li & Peter W. Nathanielsz

  4. Center for Precision Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    Laura A. Cox

  5. Geriatric Research Education and Clinical Center, Audie L. Murphy Hospital, Southwest Veterans Health Care System, San Antonio, TX, USA

    Adam B. Salmon

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  1. Daniel A. Adekunbi
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Adekunbi, D.A., Huber, H.F., Li, C. et al. Differential mitochondrial bioenergetics and cellular resilience in astrocytes, hepatocytes, and fibroblasts from aging baboons. GeroScience (2024). https://doi.org/10.1007/s11357-024-01155-7

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