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.
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
Geroscience. 2024 Oct;46(5):4443-4459. doi: 10.1007/s11357-024-01155-7. Epub 2024 Apr 12.
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-HO), 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.
生物弹性(resilience),广义上被定义为从急性挑战中恢复并回到体内平衡的能力,对于衰老生物学越来越重要。在细胞水平上,不同组织类型的细胞弹性存在差异,这些差异可能导致组织衰老速度的差异。然而,在区域、组织和个体水平上解决这些细胞类型差异存在挑战。为了解决这个问题,我们从年龄在 13.3 至 17.8 岁之间的雄性和雌性狒狒中建立了原代细胞,涵盖了不同的组织、组织区域和细胞类型,包括 (1) 来自皮肤和心脏的成纤维细胞,分为左心室 (LV)、右心室 (RV)、左心房 (LA) 和右心房 (RA);(2) 来自前额叶皮层和海马体的星形胶质细胞;和 (3) 肝细胞。原代细胞通过其细胞表面标志物进行表征,并使用 Seahorse XFe96 评估其细胞呼吸。通过修改活细胞成像方法评估细胞弹性;我们之前报道过,该方法监测氧化 (50 µM-HO)、代谢 (1 mM-葡萄糖) 和蛋白质稳态 (0.1 µM-thapsigargin) 应激后分裂细胞的增殖和恢复情况。我们注意到,即使在依赖于组织来源的相似细胞类型之间也存在显著差异,并且细胞反应的多样性是应激特异性的。例如,星形胶质细胞的耗氧率更高,对氧化应激 (OS) 的弹性比成纤维细胞和肝细胞都强。与 LV 和 LA 相比,RV 和 RA 成纤维细胞对 OS 的弹性较低。与星形胶质细胞和心脏成纤维细胞相比,皮肤成纤维细胞对蛋白质稳态应激的影响较小。未来的研究将测试这些结果与供体的年龄和发育状态之间的功能关系,作为潜在的预测标志物。
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