Calzia 2016 Abstract MitoFit Science Camp 2016
|Mitochondrial respiration shows tissue- and strain-specific aging in short- and long-lived N. furzeri strains.|
The turquoise killifish Nothobranchius furzeri is a short-lived vertebrate who inhabits transient freshwater ponds in the southeast of Africa. Due to its short lifespan this species has advanced to a vertebrate model for the biology and genetics of aging . In our present study we quantified mitochondrial respiration in brain, liver, heart, and skeletal muscle of a short- and a long-lived strain of the fish at sequential points in time along to their specific lifespan duration.
Tissue samples were obtained at day 35, 68, and 100 in fishes of the short-lived strain and at day 35, 68, 100, 147, and 287 in the long-lived animals. Mitochondrial respiration was measured in terms of LEAK-, OXPHOS-, and ET-capacities by means of the high-resolution respirometry using an Oxygraph-2k (Oroboros Instruments, Austria). Respiratory activity of the homogenized tissue samples was simultaneously supported by complex I and II substrates (malate, glutamate, pyruvate, and succinate), as well as by ADP and quantified in terms of oxygen flux [JO2] per wet weight with the unit of pmol O2/(s·mg). OXPHOS capacity was obtained as the maximum activity under all substrates and ADP, LEAK respiration by inhibition of the ATP-synthase obtained by further injection of oligomycin, and, finally, ET-capacity by titration of the uncoupler FCCP.
We found a particularly pronounced decrease in mitochondrial respiration with age in the skeletal muscle of both strains; a more moderate decrease was also observed in the brain. In contrast, mitochondrial respiration in liver and heart was almost constant over the whole lifespan duration.
Our results suggest that aging-related changes in mitochondrial respiration of the Nothobranchius furzeri fish species are organ specific. These results will be discussed in relation to the biology of aging in general, and, in particular, to the most recently identified relevance of Complex I for determining the lifespan of this species .
• O2k-Network Lab: DE Ulm Radermacher P
Labels: MiParea: Respiration Pathology: Aging;senescence
Organism: Fishes Tissue;cell: Heart, Skeletal muscle, Nervous system, Liver
Coupling state: LEAK, OXPHOS, ET Pathway: NS HRR: Oxygraph-2k Event: B2 MitoFit Science Camp 2016
1-Inst APV, Univ Hospital Ulm, 2-Genome Analysis Group, FLI Jena. - [email protected]
- Reichwald K, Petzold A, Koch P, Downie BR, Hartmann N, Pietsch S, Baumgart M, Chalopin D, Felder M, Bens M, Sahm A, Szafranski K, Taudien S, Groth M, Arisi I, Weise A, Bhatt SS, Sharma V, Kraus JM, Schmid F, Priebe S, Liehr T, Goerlach M, Than ME, Hiller M, Kestler HA, Volff JN, Schartl M, Cellerino A, Englert C, Platzer M (2015) Insights into sex chromosome evolution and aging from the genome of a short-lived fish. Cell 163:1527-38.
- Baumgart M, Priebe S, Groth M, Hartmann N, Menzel U, Pandolfini L, Koch P, Felder M, Ristow M, Englert C, Guthke R, Platzer M, Cellerino A (2016) Longitudinal RNA-seq analysis of vertebrate aging identifies mitochondrial complex I as a small-molecule-sensitive modifier of lifespan. Cell Syst 2:122-32.