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Research Paper|Volume 6, Issue 6|pp 468—480

The age related markers lipofuscin and apoptosis show different genetic architecture by QTL mapping in short-lived Nothobranchius fish

Enoch Ng'oma1, Kathrin Reichwald2, Alexander Dorn1, Michael Wittig3, Tobias Balschun4, Andre Franke3, Matthias Platzer2, Allesandro Cellerino1,5
  • 1Biology of Ageing, Leibniz Institute for Age Research – Fritz Lipmann Institute, 07745 Jena, Germany
  • 2Genome Analysis, Leibniz Institute for Age Research – Fritz Lipmann Institute, 07745 Jena, Germany
  • 3Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany
  • 4Hufeland Klinikum Mühlhausen, Institut für Infektiologie und Pathobiologie, 99974 Mühlhausen, Germany
  • 5Neurobiology Laboratory, Scuola Normale Superiore, 56124 Pisa, Italy
Received: April 14, 2014Accepted: May 6, 2014Published: May 12, 2014
https://doi.org/10.18632/aging.100660

Copyright: © 2014 Ng'oma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Annual fish of the genus Nothobranchius show large variations in lifespan and expression of age-related phenotypes between closely related populations. We studied N. kadleci and its sister species N. furzeri GRZ strain, and found that N.kadleci is longer-lived than the N. furzeri. Lipofuscin and apoptosis measured in the liver increased with age in N. kadleci with different profiles: lipofuscin increased linearly, while apoptosis declined in the oldest animals. More lipofuscin (P < 0.001) and apoptosis (P < 0.001) was observed in N. furzeri than in N. kadleci at 16w age. Lipofuscin and apoptotic cells were then quantified in hybrids from the mating of N. furzeri to N. kadleci. F1 individuals showed heterosis for lipofuscin but additive effects for apoptosis. These two age-related phenotypes were not correlated in F2 hybrids. Quantitative trait loci analysis of 287 F2 fish using 237 markers identified two QTL accounting for 10% of lipofuscin variance (P < 0.001) with overdominance effect. Apoptotic cells revealed three significant- and two suggestive QTL explaining 19% of variance (P < 0.001), showing additive and dominance effects, and two interacting loci. Our results show that lipofuscin and apoptosis are markers of different age-dependent biological processes controlled by different genetic mechanisms.