Ehinger 2024 NPJ Aging
| Ehinger JK, Westerlund E, Åsander Frostner E, Karlsson M, Paul G, Sjövall F, Elmér E (2024) Mitochondrial function in peripheral blood cells across the human lifespan. NPJ Aging 10:10. https://doi.org/10.1038/s41514-023-00130-4 |
Ehinger Johannes K, Westerlund Emil, Aasander Frostner Eleonor, Karlsson Michael, Paul Gesine, Sjoevall Fredrik, Elmer Eskil (2024) NPJ Aging
Abstract: Mitochondrial dysfunction is considered a hallmark of aging. Up to now, a gradual decline of mitochondrial respiration with advancing age has mainly been demonstrated in human muscle tissue. A handful of studies have examined age-related mitochondrial dysfunction in human blood cells, and only with small sample sizes and mainly in platelets. In this study, we analyzed mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and platelets from 308 individuals across the human lifespan (0-86 years). In regression analyses, with adjustment for false discovery rate (FDR), we found age-related changes in respiratory measurements to be either small or absent. The main significant changes were an age-related relative decline in complex I-linked respiration and a corresponding rise of complex II-linked respiration in PBMCs. These results add to the understanding of mitochondrial dysfunction in aging and to its possible role in immune cell and platelet senescence.
• Bioblast editor: Plangger M • O2k-Network Lab: SE Lund Elmer E
Discussion
- Quote {see Comments}: 'The N/NS pathway control ratio (N/NS PCR) reflects the relative contribution of the N-pathway or CI-linked respiration. The S/NS-pathway control ratio (S/NS PCR) reflects the relative contribution of the S-pathway or CII-linked respiration.{*} The RCR reflects the coupling efficiency of the ETS.{**} In contrast to the other respiratory measurements, which were normalized to cell count, respiratory ratios are a way of normalizing results to mitochondrial content{***}, providing qualitative indices of mitochondrial function. Supplementary Table 1{****} describes how each ratio was calculated.’
- Comments by Gnaiger Erich (talk) 08:08, 21 November 2024 (CET)
- {*} This is not true for all cases which show incomplete additivitiy – see Chapter 7 in BEC2020.2
- {**} The RCR requires transformation to become an index of ‘efficiency’ – see Chapter 3 (page 40) in BEC2020.2
- {***} On the contrary, respiratory ratios are a way of normalizing results independent of mitochondrial content – see Chapter 3 (page 37) in BEC2020.2: “Flux ratios are independent of (1) cell count, wet or dry mass, (2) mt-content of cells or tissues, ..”.
- {****} In Supplementary Tables 1 and 2, proper citations [1], [2] are missing.
- 'malate and pyruvate were added at saturating concentrations (5 mM each)' - Malate 5 mM exerts a strong inhibitory effect on succinate-pathway capacity. We recommend a lower malate concentration (2 mM).
- 'the ATP synthase was inhibited by oligomycin (1 µg/ml)' - Oligomycin 1 µg/mL (Omy; 1.25 µM) may exert an inhibitory effect on ET-capacity. We recommend Omy concentrations in the range of 10 to 50 nM (Doerrier et al 2018; Vernerova et al 2021).
Labels: MiParea: Respiration
Pathology: Aging;senescence
Organism: Human Tissue;cell: Blood cells Preparation: Permeabilized cells, Intact cells
Coupling state: ET, LEAK, ROUTINE, OXPHOS
Pathway: N, S, NS, ROX
HRR: Oxygraph-2k
2024-11, PBMCs
