Fig 1: Chronic hypoxia induces premature aging in fetal kidneys.A, a heatmap showing all significantly changed proteins for the GO term “Aging” and their induction or repression in hypoxia, depicted in decreasing order of protein abundance. B and C, the Abundance of the antiaging proteins klotho (B, unpaired two-tailed t test with Welch’s correction, p = 0.0239) and sirtuin 6 (C, unpaired two-tailed t test with Welch’s correction, p = 0.0004) was reduced in renal tissue from hypoxic fetuses. D and E, accordingly, serum levels of soluble Klotho (sKL) (D, unpaired two-tailed t test, p = 0.0032) and sirtuin 6 (E, unpaired two-tailed t test, p = 0.0245) were also reduced in hypoxic fetuses. F and G, these reductions of sKL (F, unpaired two-tailed t test, p = 0.0087) and sirtuin 6 (G, unpaired two-tailed t test, p = 0.0003) were still present in the serum of hypoxic offspring at 15 months. H, for klotho this seems to be due to reduced mRNA expression in the kidney (H, unpaired two-tailed t test, p = 0.0176). I, whereas renal Sirt6 mRNA expression was not changed between normoxic and hypoxic offspring at 15 months (unpaired two-tailed t test, p = 0.9423).
Fig 2: The effect of chronic hypoxia on serum levels of klotho and sirtuin 6 is evolutionary conserved. Human serum samples from a controlled study of nine healthy volunteers (eight males, one female) were collected 2 weeks before (sea level, SL), at three time points while at 3454 m (HA3, HA9, HA28), and 1, 7 and 14 days upon returning to SL (RSL1, RSL7, RSL14). A, human sKL concentrations quickly declined at HA and reached statistical significance at HA28 (RM one-way ANOVA with the Geisser–Greenhouse correction, Dunnett’s multiple comparisons test; all comparisons versus SL control group; p = 0.0066). Upon descent, sKL levels rapidly returned to SL levels or higher with a temporary peak around RSL7 (p = 0.2986). B, on the other hand, the serum concentrations of human SIRT6 were significantly repressed from H28 to RSL7 (RM one-way ANOVA with the Geisser–Greenhouse correction, Dunnett’s multiple comparisons test; all comparisons versus SL control group; for HA28: p = 0.002, for RSL1: p = 0.0001, for RSL7: p = 0.0063) and only started to rise again slowly at RSL14 (p = 0.7107).
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