Kristina Gebhardt, Anne Hebecker, Natascha Sommer, Robert Ringseis, Klaus Eder, Magdalena Huber, Hartmann Raifer, Karsten Krüger, Christopher Weyh
{"title":"健康老年人PBMCs线粒体呼吸及其与免疫、健康和代谢风险的关系","authors":"Kristina Gebhardt, Anne Hebecker, Natascha Sommer, Robert Ringseis, Klaus Eder, Magdalena Huber, Hartmann Raifer, Karsten Krüger, Christopher Weyh","doi":"10.1002/jcp.70096","DOIUrl":null,"url":null,"abstract":"<p>Mitochondrial function plays a central role in regulating immunological and metabolic processes, particularly during successful aging. This cross-sectional study aimed to investigate associations between mitochondrial respiration of peripheral blood mononuclear cells (PBMCs; MR<sub>PBMC</sub>) and key markers of immune function, systemic inflammation, and metabolic health in a cohort of healthy older adults. Sixteen healthy, physically active participants aged > 55 years (male: <i>n</i> = 9; female: <i>n</i> = 7; age: 64 ± 3.7 years; BMI: 24.3 ± 2.9; VO<sub>2peak</sub>: 31.1 ± 8.8 mL/min/kg) were recruited. Participants were tested for their maximal oxygen uptake (VO<sub>2peak</sub>) as well as cardiovascular and metabolic risk factors. Venous fasting blood samples were collected. For further analysis, MR<sub>PBMC</sub> was measured using the Oroboros O2k-Oxygraph. T cell subsets were analyzed by flow cytometry, serum cytokines by LUMINEX assays, and gene expression by qPCR analysis. We found positive associations between basal and maximal MR<sub>PBMC,</sub> and the percentage of CD4<sup>+</sup> T cells, with a notable link to naïve CD4<sup>+</sup> T cells (<i>p</i> < 0.05). Maximal MR<sub>PBMC</sub> was negatively associated with proportion of effector memory CD4<sup>+</sup> T cells (<i>p</i> < 0.05). Basal MR<sub>PBMC</sub> showed negative associations with pro-inflammatory serum cytokine tumor necrosis factor alpha (TNF-α), while maximal MR<sub>PBMC</sub> was positively associated with interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor (VEGF) (<i>p</i> < 0.05). Intracellular signaling markers, including mRNA level of signal transducer and activator of transcription 3 (STAT3), also showed positive associations with maximal MR<sub>PBMC</sub> (<i>p</i> < 0.05). No correlations were found for variables such as cardiorespiratory fitness, IL-6, and IL-10. In conclusion, PBMC mitochondrial bioenergetics are linked to T cell subpopulations and systemic inflammation in healthy older adults. Higher mitochondrial respiration reflecting better mitochondrial function favors a more naïve CD4<sup>+</sup> T cell distribution. In contrast, lower mitochondrial function was observed in individuals with a more pro-inflammatory profile, suggesting a potential relationship between immune status and mitochondrial bioenergetics in older adults.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 9","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70096","citationCount":"0","resultStr":"{\"title\":\"PBMCs Mitochondrial Respiration and Its Relation to Immunity, Fitness, and Metabolic Risk in the Healthy Elderly\",\"authors\":\"Kristina Gebhardt, Anne Hebecker, Natascha Sommer, Robert Ringseis, Klaus Eder, Magdalena Huber, Hartmann Raifer, Karsten Krüger, Christopher Weyh\",\"doi\":\"10.1002/jcp.70096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Mitochondrial function plays a central role in regulating immunological and metabolic processes, particularly during successful aging. This cross-sectional study aimed to investigate associations between mitochondrial respiration of peripheral blood mononuclear cells (PBMCs; MR<sub>PBMC</sub>) and key markers of immune function, systemic inflammation, and metabolic health in a cohort of healthy older adults. Sixteen healthy, physically active participants aged > 55 years (male: <i>n</i> = 9; female: <i>n</i> = 7; age: 64 ± 3.7 years; BMI: 24.3 ± 2.9; VO<sub>2peak</sub>: 31.1 ± 8.8 mL/min/kg) were recruited. Participants were tested for their maximal oxygen uptake (VO<sub>2peak</sub>) as well as cardiovascular and metabolic risk factors. Venous fasting blood samples were collected. For further analysis, MR<sub>PBMC</sub> was measured using the Oroboros O2k-Oxygraph. T cell subsets were analyzed by flow cytometry, serum cytokines by LUMINEX assays, and gene expression by qPCR analysis. We found positive associations between basal and maximal MR<sub>PBMC,</sub> and the percentage of CD4<sup>+</sup> T cells, with a notable link to naïve CD4<sup>+</sup> T cells (<i>p</i> < 0.05). Maximal MR<sub>PBMC</sub> was negatively associated with proportion of effector memory CD4<sup>+</sup> T cells (<i>p</i> < 0.05). Basal MR<sub>PBMC</sub> showed negative associations with pro-inflammatory serum cytokine tumor necrosis factor alpha (TNF-α), while maximal MR<sub>PBMC</sub> was positively associated with interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor (VEGF) (<i>p</i> < 0.05). Intracellular signaling markers, including mRNA level of signal transducer and activator of transcription 3 (STAT3), also showed positive associations with maximal MR<sub>PBMC</sub> (<i>p</i> < 0.05). No correlations were found for variables such as cardiorespiratory fitness, IL-6, and IL-10. In conclusion, PBMC mitochondrial bioenergetics are linked to T cell subpopulations and systemic inflammation in healthy older adults. Higher mitochondrial respiration reflecting better mitochondrial function favors a more naïve CD4<sup>+</sup> T cell distribution. In contrast, lower mitochondrial function was observed in individuals with a more pro-inflammatory profile, suggesting a potential relationship between immune status and mitochondrial bioenergetics in older adults.</p>\",\"PeriodicalId\":15220,\"journal\":{\"name\":\"Journal of Cellular Physiology\",\"volume\":\"240 9\",\"pages\":\"\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70096\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cellular Physiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jcp.70096\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cellular Physiology","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jcp.70096","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
PBMCs Mitochondrial Respiration and Its Relation to Immunity, Fitness, and Metabolic Risk in the Healthy Elderly
Mitochondrial function plays a central role in regulating immunological and metabolic processes, particularly during successful aging. This cross-sectional study aimed to investigate associations between mitochondrial respiration of peripheral blood mononuclear cells (PBMCs; MRPBMC) and key markers of immune function, systemic inflammation, and metabolic health in a cohort of healthy older adults. Sixteen healthy, physically active participants aged > 55 years (male: n = 9; female: n = 7; age: 64 ± 3.7 years; BMI: 24.3 ± 2.9; VO2peak: 31.1 ± 8.8 mL/min/kg) were recruited. Participants were tested for their maximal oxygen uptake (VO2peak) as well as cardiovascular and metabolic risk factors. Venous fasting blood samples were collected. For further analysis, MRPBMC was measured using the Oroboros O2k-Oxygraph. T cell subsets were analyzed by flow cytometry, serum cytokines by LUMINEX assays, and gene expression by qPCR analysis. We found positive associations between basal and maximal MRPBMC, and the percentage of CD4+ T cells, with a notable link to naïve CD4+ T cells (p < 0.05). Maximal MRPBMC was negatively associated with proportion of effector memory CD4+ T cells (p < 0.05). Basal MRPBMC showed negative associations with pro-inflammatory serum cytokine tumor necrosis factor alpha (TNF-α), while maximal MRPBMC was positively associated with interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor (VEGF) (p < 0.05). Intracellular signaling markers, including mRNA level of signal transducer and activator of transcription 3 (STAT3), also showed positive associations with maximal MRPBMC (p < 0.05). No correlations were found for variables such as cardiorespiratory fitness, IL-6, and IL-10. In conclusion, PBMC mitochondrial bioenergetics are linked to T cell subpopulations and systemic inflammation in healthy older adults. Higher mitochondrial respiration reflecting better mitochondrial function favors a more naïve CD4+ T cell distribution. In contrast, lower mitochondrial function was observed in individuals with a more pro-inflammatory profile, suggesting a potential relationship between immune status and mitochondrial bioenergetics in older adults.
期刊介绍:
The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.