Fig. 5: OxPhos defects trigger hypersecretion of metabokines and age-related cytokines.

a Cytokine dynamics across the lifespan measured on two multiplexes (Luminex) arrays. Cytokine levels are normalized to the number of cells at the time of sampling, shown as Log₂ median-centered for each cytokine; samples with undetectable values are shown as gray cells. Columns represent repeated measures (n = 6–8) along the lifespan of each control and SURF1 donor (n = 3 per group). b Comparison of maximum cytokine concentration reached in each of the SURF1 and healthy control donors, showing general upregulation of most metabokines and cytokines. The value for TGF-α is heavily influenced by a single very high value in Donor 3. c Cell-free media GDF15 concentration time course as measured on the Cytokine array. Inset compares early release between 20 and 80 days. d Media IL-6 levels across the cellular lifespan by enzyme-linked immunosorbent assay (ELISA), normalized to the number of cells at the time of sampling. e Media GDF15 levels across the cellular lifespan measured by ELISA, normalized to the number of cells at the time of sampling. Samples with non-detectable values (N.D.) are shown as zero values. f Cell-free mitochondrial DNA (cf-mtDNA) dynamics across the cellular lifespan using qPCR, normalized to the number of cells at the time of sampling. n = 3 per group, 6–13 timepoints per condition. Data are means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, mixed effects model (fixed effect of Control/SURF1/Oligo group and days grown, random effects of donor or cell line). Abbreviations: CCL7 C-C motif chemokine ligand 7, IL-8 interleukin 8, CHI3L1 chitinase-3-like protein 1, MMP7 Matrix metallopeptidase 7, IL-6 Interleukin 6, IGFBP-rp1 Insulin-like growth factor binding protein 7, TNF-RII tumor necrosis factor receptor superfamily member 1B, TGF-α tumor growth factor alpha, IFN-γ interferon-gamma, TNFRSF9 TNF receptor superfamily member 9, GDF-15 growth differentiation factor 15, TNF-β tumor necrosis factor beta, Fas Fas cell surface death receptor, CCL3 C-C motif chemokine ligand 7, FSTL1 Follistatin like 1, CCL23 C-C motif chemokine ligand 23, TIMP-1 tissue inhibitor of metallopeptidase 1, CD163 CD163 antigen, Lumican keratan sulfate proteoglycan Lumican, IL-18 interleukin-18, CXCL16 C-X-C motif chemokine ligand 16, Fetuin A alpha 2-HS glycoprotein, ALCAM activated leukocyte cell adhesion molecule, TNF-RI TNF receptor superfamily member 1A, PCSK9 proprotein convertase subtilisin/kexin type 9, TFPI tissue factor pathway inhibitor.