title: The age related markers lipofuscin and apoptosis show different genetic architecture by QTL mapping in short-lived Nothobranchius fish.
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. F₁individuals 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.
authors.affiliation: Biology of Ageing, Leibniz Institute for Age Research - Fritz Lipmann Institute, 07745 Jena, Germany.
authors.forename: Enoch
authors.initials: E
authors.lastname: Ng'oma
authors.affiliation: Genome Analysis, Leibniz Institute for Age Research - Fritz Lipmann Institute, 07745 Jena, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reichwald
authors.affiliation: Biology of Ageing, Leibniz Institute for Age Research - Fritz Lipmann Institute, 07745 Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dorn
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wittig
authors.affiliation: Hufeland Klinikum Mühlhausen, Institut für Infektiologie und Pathobiologie, 99974 Mühlhausen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Balschun
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Genome Analysis, Leibniz Institute for Age Research - Fritz Lipmann Institute, 07745 Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.affiliation: Biology of Ageing, Leibniz Institute for Age Research - Fritz Lipmann Institute, 07745 Jena, Germany. Neurobiology Laboratory, Scuola Normale Superiore, 56124 Pisa, Italy.
authors.forename: Allesandro
authors.initials: A
authors.lastname: Cellerino
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015415:Biomarkers / Q000032:analysis; D003532:Cyprinodontiformes / Q000235:genetics*; D020287:In Situ Nick-End Labeling; D008062:Lipofuscin / Q000032:analysis* / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D040641:Quantitative Trait Loci
chemical_list: D015415:Biomarkers; D008062:Lipofuscin
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