Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus
| Autor: | Takashi Yokota, Nima Borhan Fakouri, Steen Larsen, Flemming Dela, Kirsten Thomsen, Claus Desler, Christine Elisabeth Regnell, Lene Juel Rasmussen, Linda H. Bergersen, Niloofar Sherazi, Mahdi Hasan-Olive, Martin Lauritzen |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Aging medicine.medical_specialty Mitochondrial DNA Cell Respiration Hippocampus Mice Transgenic Biology Mitochondrial Size DNA Mitochondrial Cockayne syndrome 03 medical and health sciences Internal medicine Genotype Respiration medicine Animals RNA Messenger Poly-ADP-Ribose Binding Proteins Genetics Messenger RNA Electron Transport Complex I General Neuroscience DNA Helicases Brain Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Frontal Lobe Mitochondria Cortex (botany) DNA Repair Enzymes 030104 developmental biology Endocrinology Neurology (clinical) Geriatrics and Gerontology Developmental Biology |
| Zdroj: | Neurobiology of Aging. 61:215-224 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2017.08.004 |
| Popis: | Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSBm/m) and C57Bl/6 (WT) controls and comparing young (2–5 months) to middle-aged mice (13–14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSBm/m hippocampus, but not in CSBm/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSBm/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging. |
| Databáze: | OpenAIRE |
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