The impact of mitochondria on aging and lifespan in the short-lived killifish Nothobranchius furzeri
Final Report Abstract
The initial goal of this grant was to analyze the role of the mitochondria in aging of the shortlived killifish Nothobranchius furzeri. The underlying hypothesis was that mitochondrial decline contributes to the aging process in this species. Conversely, enhanced mitochondrial biogenesis and function should alleviate some of the aging-associated symptoms and eventually might even result in a prolonged lifespan. However, the data that we have generated in the context of this proposal did not support this notion. This is not so say that the hypothesis is wrong, but it certainly requires more work to assess the role of the mitochondria for aging in N. furzeri. In a second aspect of this proposal on aging in N. furzeri we have used TALENs and CRISPR/Cas9 to generate mutant alleles of genes that are involved in aging. Two genes that we focused on are tert, encoding the functional subunit of telomerase and the tumor suppressor p53. In both cases we could establish loss-of-function alleles that, when crossed to homozygosity, resulted in a shortened lifespan. Although the respective characterizations have not yet been finished, our data so far suggest that in case of tert the shortened lifespan results from tissue atrophy, while p53 mutants suffer from tumorigenesis. We are currently in the process of finishing the phenotypic and molecular characterization of the mutant animals, write the respective manuscripts and employ the mutants for further studies on aging as well as regeneration.
Publications
- (2015) Age-dependent decline of fin regenerative capacity in the short-lived fish Nothobranchius furzeri. Aging Cell, 14, 857-866
Wendler, S., Hartmann, N., Hoppe, B. and Englert, C.
(See online at https://doi.org/10.1111/acel.12367) - (2015) Insights into sex chromosome evolution and aging from the genome of a short-lived fish. Cell, 163, 1527–1538
Reichwald, K., Petzold, A., Koch, P., Downie, B.R., 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, S.S., Sharma, V., Kraus, J.M., Schmid, F., Priebe, S., Liehr, T., Görlach, M., Than, M., Hiller, M., Kestler, H.A., Volff, J.-N., Schartl, M., Cellerino, A., Englert, C., & Platzer, M.
(See online at https://doi.org/10.1016/j.cell.2015.10.071) - Generation and characterization of telomerase (tert) mutants in Nothobranchius furzeri. PhD
Peter Singer
