Mihriban Özsoy1, Franz A Zimmermann2, René G Feichtinger2, Johannes A Mayr1, Barbara Kofler2, Daniel Neureiter3, Eckhard Klieser3, Sebastian Schütz4, Daniel Weghuber5, Anna M Schneider1. 1. Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria. 2. Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria; Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria. 3. Department of Pathology, Paracelsus Medical University, Salzburg, Austria. 4. Department of Mathematics, Paris Lodron University, Salzburg, Austria. 5. Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria. Electronic address: d.weghuber@salk.at.
Abstract
OBJECTIVE: Mitochondria produce cellular energy via oxidative phosphorylation (OXPHOS), mediated by respiratory chain complexes I to IV and ATP synthase (complex V). Mitochondrial respiratory complexes have been shown to decline with age in several tissues. As the intestinal epithelium is a tissue with a high energy demand, the aim of the present study was to establish whether the expression profile of OXPHOS subunits in the intestinal mucosa changes during the aging process. DESIGN: Biopsies of intestinal mucosa with no evidence of endoscopic or histomorphologic abnormalities, taken from 55 patients (mean age 42 years, age range 4-82 years; 62% female), were divided into four age groups (4-19, 20-39, 40-59, ≥60 years). Sections from different intestinal segments (terminal ileum, ascending colon, and sigmoid colon/rectum) were stained immunohistochemically (IHC) for subunits of OXPHOS complexes I-V and the voltage-dependent anion-selective channel 1 protein (VDAC1, porin), a marker of mitochondrial mass. Scores for IHC staining were determined by multiplication of the staining intensity and the percentage of positive cells. In addition, the numbers of intestinal crypts staining positive, partly positive, and negative were assessed. RESULTS: The average protein expression levels of OXPHOS subunits increased continuously from childhood onward, peaked in persons aged 20 to 59 years, and declined thereafter. This was seen for complexes II to V in the terminal ileum, complexes I to V in the ascending colon, and complexes I to IV in the sigmoid colon/rectum. Across all age groups, no effect of age on expression of the porin subunit VDAC1 was detected. The number of complex I- and IV-negative crypts in different intestinal segments increased with age. CONCLUSION: The protein expression levels of OXPHOS complexes increases from childhood onward and declines in elderly individuals, while the numbers of crypts with partial or complete loss of expression of complexes I and IV increase continuously with age. These data suggest that the continued reductions in the levels of mitochondrial OXPHOS complexes in crypts might be compensated in adulthood, but that, ultimately, reduced expression levels occur in persons aged 60 years and older. These findings raise two important questions: first, can the process of aging could be delayed through (pharmacological) intervention of mitochondrial pathways, and second, pathophysiologically, are these findings associated with disorders of the intestinal mucosa, e.g. inflammation?
OBJECTIVE: Mitochondria produce cellular energy via oxidative phosphorylation (OXPHOS), mediated by respiratory chain complexes I to IV and ATP synthase (complex V). Mitochondrial respiratory complexes have been shown to decline with age in several tissues. As the intestinal epithelium is a tissue with a high energy demand, the aim of the present study was to establish whether the expression profile of OXPHOS subunits in the intestinal mucosa changes during the aging process. DESIGN: Biopsies of intestinal mucosa with no evidence of endoscopic or histomorphologic abnormalities, taken from 55 patients (mean age 42 years, age range 4-82 years; 62% female), were divided into four age groups (4-19, 20-39, 40-59, ≥60 years). Sections from different intestinal segments (terminal ileum, ascending colon, and sigmoid colon/rectum) were stained immunohistochemically (IHC) for subunits of OXPHOS complexes I-V and the voltage-dependent anion-selective channel 1 protein (VDAC1, porin), a marker of mitochondrial mass. Scores for IHC staining were determined by multiplication of the staining intensity and the percentage of positive cells. In addition, the numbers of intestinal crypts staining positive, partly positive, and negative were assessed. RESULTS: The average protein expression levels of OXPHOS subunits increased continuously from childhood onward, peaked in persons aged 20 to 59 years, and declined thereafter. This was seen for complexes II to V in the terminal ileum, complexes I to V in the ascending colon, and complexes I to IV in the sigmoid colon/rectum. Across all age groups, no effect of age on expression of the porin subunit VDAC1 was detected. The number of complex I- and IV-negative crypts in different intestinal segments increased with age. CONCLUSION: The protein expression levels of OXPHOS complexes increases from childhood onward and declines in elderly individuals, while the numbers of crypts with partial or complete loss of expression of complexes I and IV increase continuously with age. These data suggest that the continued reductions in the levels of mitochondrial OXPHOS complexes in crypts might be compensated in adulthood, but that, ultimately, reduced expression levels occur in persons aged 60 years and older. These findings raise two important questions: first, can the process of aging could be delayed through (pharmacological) intervention of mitochondrial pathways, and second, pathophysiologically, are these findings associated with disorders of the intestinal mucosa, e.g. inflammation?
Authors: Anna M Schneider; Mihriban Özsoy; Franz A Zimmermann; Susanne M Brunner; René G Feichtinger; Johannes A Mayr; Barbara Kofler; Daniel Neureiter; Eckhard Klieser; Elmar Aigner; Sebastian Schütz; Nathalie Stummer; Wolfgang Sperl; Daniel Weghuber Journal: Oxid Med Cell Longev Date: 2022-01-06 Impact factor: 6.543
Authors: Monica De Luise; Luisa Iommarini; Lorena Marchio; Greta Tedesco; Camelia Alexandra Coadă; Andrea Repaci; Daniela Turchetti; Maria Lucia Tardio; Nunzio Salfi; Uberto Pagotto; Ivana Kurelac; Anna Maria Porcelli; Giuseppe Gasparre Journal: Cells Date: 2021-10-28 Impact factor: 6.600
Authors: Anna M Schneider; Mihriban Özsoy; Franz A Zimmermann; René G Feichtinger; Johannes A Mayr; Barbara Kofler; Wolfgang Sperl; Daniel Weghuber; Katharina Mörwald Journal: Oxid Med Cell Longev Date: 2020-08-18 Impact factor: 6.543