title: Mitochondrial DNA copy number and function decrease with age in the short-lived fish Nothobranchius furzeri.
abstract: Among vertebrates that can be kept in captivity, the annual fish Nothobranchius furzeri possesses the shortest known lifespan. It also shows typical signs of aging and is therefore an ideal model to assess the role of different physiological and environmental parameters on aging and lifespan determination. Here, we used Nothobranchius furzeri to study whether aging is associated with mitochondrial DNA (mtDNA) alterations and changes in mitochondrial function. We sequenced the complete mitochondrial genome of N. furzeri and found an extended control region. Large-scale mtDNA deletions have been frequently described to accumulate in other organisms with age, but there was no evidence for the presence of detectable age-related mtDNA deletions in N. furzeri. However, mtDNA copy number significantly decreased with age in skeletal muscle, brain, liver, skin and dorsal fin. Consistent with this finding, expression of Pgc-1α that encodes a transcriptional coactivator of mitochondrial biogenesis and expression of Tfam and mtSsbp both encoding mtDNA binding factors was downregulated with age. The investigation of possible changes in mitochondrial function revealed that the content of respiratory chain complexes III and IV was reduced in skeletal muscle with age. In addition, ADP-stimulated and succinate-dependent respiration was decreased in mitochondria of old fish. These findings suggest that despite the short lifespan, aging in N. furzeri is associated with a decline in mtDNA copy number, the downregulation of mtDNA-associated genes and an impairment of mitochondrial function.
authors.affiliation: Department of Molecular Genetics, Leibniz Institute for Age Research-Fritz Lipmann Institute (FLI), Beutenbergstrasse 11, Jena, Germany. hartmann@fli-leibniz.de
authors.forename: Nils
authors.initials: N
authors.lastname: Hartmann
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reichwald
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.forename: Stefan
authors.initials: S
authors.lastname: Dröse
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmeisser
authors.forename: Claudia
authors.initials: C
authors.lastname: Lück
authors.forename: Christin
authors.initials: C
authors.lastname: Hahn
authors.forename: Michael
authors.initials: M
authors.lastname: Graf
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gausmann
authors.forename: Eva
authors.initials: E
authors.lastname: Terzibasi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cellerino
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.forename: Christoph
authors.initials: C
authors.lastname: Englert
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D019069:Cell Respiration; D003532:Cyprinodontiformes / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000032:analysis* / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D018507:Gene Expression Regulation, Developmental; D054629:Genome, Mitochondrial; D008136:Longevity; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008962:Models, Theoretical; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D014157:Transcription Factors