Prof. Dr. Dario Riccardo Valenzano

Research Group Leader - MPI for Biology of Aging

Evolutionary and Experimental Biology of Aging

Our research: Our lab research is focused on identifying the evolutionary genomic basis of vertebrate longevity and aging. We use the turquoise killifish (Nothobranchius furzeri) as a reference model organism, a fish characterized by embryonic diapause, rapid sexual maturation and the shortest lifespan among all captive vertebrates (4 months in the GRZ strain). Taking advantage of the natural diversity in aging and longevity phenotypes among different turquoise killifish populations, we use comparative genomics and population genetics to investigate the evolution of the genomic bases of extreme lifespan phenotypes. Since killifish have highly complex gut microbial commensal communities and are equipped with a lymphocyte-based adaptive immune system, we recently started to investigate how the gut microbial population interacts with the host immune function to modulate the aging process. We additionally develop theoretical models and numerical simulations to simulate the evolution of biological aging under different constraints and ask the fundamental question of how natural selection shapes the evolution of different life history traits, such as growth and individual survival.

Our successes: Over the past few years, we have developed a toolkit to promote the turquoise killifish as a novel model organism. These tools include the first microsatellite-based linkage map, a high-resolution SNP-based linkage map, a fully sequenced, assembled and annotated genome (work started at and in collaboration with the Brunet lab at Stanford University), several assembled transcriptomes, and efficient transgenesis via the Tol2 transposase, which enabled us to generate a number of laboratory transgenic lines for functional studies. Additionally, we identified the sex-determination system of this species and mapped the genomic regions associated with colour and captive survival, discovering that, although longevity in this species has a complex genetic architecture, a locus placed on the sex chromosome is associated with major changes in individual survival. Using comparative genomics, we also identified several genes and genomic regions that have a strong signature for positive selection in this species, which are possibly responsible for the unique life history adaptations of this species. We regularly conduct fieldwork in Zimbabwe, where we established an official collaboration with the Gonarezhou National Park, which hosts the natural environment of this species. We have established several wild-derived fish laboratory strains, which provide the basis for genetic mapping studies aimed at dissecting the genetic architecture of natural polymorphisms.

Our goals: Our research aims to answer the fundamental biological question of what are the genomic changes associated with the evolution of short/long lifespan and rapid/slow aging in nature. Additionally, using the shortest-lived vertebrate that can be raised in a laboratory, we aim at identifying novel methods to modulate vertebrate aging and longevity acting on the gut microbiota-immune system axis.

Our methods/techniques: We combine experimental approaches, which include genetic mapping, fish transgenesis and high-throughput sequencing, with sophisticated computational approaches, which include computer simulations, genome and transcriptome assembly, as well as state-of-the-art statistical approaches to population genetics. Furthermore, we continuously develop novel molecular and computational methods to reach our research goals.


Figure 1: Circus plot of the African turquoise killifish (Nothobranchius furzeri) genome and linkage map representing genomic regions associated with individual fish survival in captivity. From the outermost ring inwards: genome (purple segments), Radseq markers (purple bars), mapped genome scaffolds (coloured bars) and genetic association with survival (red dots and black ring representing genome-wide significant threshold). The linkage map and the association with individual survival is computed on the F2 generation of a genetic cross between a short-lived strain (GRZ) and a long-lived strain (MZM-0703).

Figure 2: Two adult male turquoise killifish (Nothobranchius furzeri) of the yellow morph (above) and red morph (below) variety