Universität zu Köln

Popkes, Miriam Lea (2021). Deciphering the spatiotemporal dynamics of intestinal aging in vertebrates using the African turquoise killifish. PhD thesis, Universität zu Köln.

Preview

PDF THESIS_FINAL_FINAAAAAAAL_Feb2022_formatcorrect_OhneCV.pdf Download (39MB) | Preview

Abstract

Aging is the major risk factor for many top-killing diseases and represents a problem for both the individual and the society. How the aging process is influenced and causally connected to microbiota is an emerging research area, with far-reaching findings obtained within the past few years. However, major underlying connections still remain elusive, in part hindered by a lack of suitable experimental model systems. The turquoise killifish is an ideal model to fill this gap and study microbiota in the context of aging, as it uniquely combines a very short lifespan with vertebrate features, such as a complex gut microbiota. However, knowledge about the killifish intestinal characteristics and gut microbiota is largely absent. Important key aspects I address include a detailed definition of aging dynamics, a characterization of gut compartmentalization and sex-specific intestinal traits, as well as the question whether non-invasive stool samples could be experimentally utilized for assessment of gut microbiota features. I thus set out to characterize killifish spatiotemporal aging dynamics and sex-specific intestinal microbial and molecular patterns by performing multi-omics analyses on intestinal sections of young and old, male and female killifish. I found strong evidence for a compartmentalization of the killifish intestine on a molecular and morphological level, with specific functions that can also be found in the mammalian intestine. Surprisingly, I did not observe section-specific microbial communities in contrast to findings from other animals including fish. I detected compelling evidence for extracellular matrix restructuring in the aged killifish intestine, with an accumulation of collagen and an increase in muscle thickness, possibly impeding the intestinal function in old fish. For the first time, I showed that the killifish intestine exhibits sex-specific molecular traits, especially concerning the coagulation process. Moreover, I asked whether non-invasive stool samples can be used as a proxy for gut microbiota by collecting microbiota samples of stool, intestinal and food samples. In addition, I set out to explore whether stool samples can be utilized to build models predicting fish age or remaining life by conducting a longitudinal collection of individual stool samples along killifish life. Excitingly, I discovered shared microbial features between stool and gut microbiota and showed for the first time that a series of stool microbial samples in combination with a machine learning approach allows prediction of both age and lifespan. My studies not only set the ground for future research on killifish gut microbiota, but provide novel promising results highlighting the importance of gut microbiota research in the context of aging.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Popkes, Miriam Lea UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-557259
Date:	21 May 2021
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Außeruniversitäre Forschungseinrichtungen > MPI for Biology of Ageing
Subjects:	Natural sciences and mathematics
Uncontrolled Keywords:	Keywords Language Microbiota UNSPECIFIED turquoise killifish UNSPECIFIED nothobranchius furzeri UNSPECIFIED metabolomics UNSPECIFIED intestine UNSPECIFIED aging UNSPECIFIED
Date of oral exam:	3 August 2021
Referee:	Name Academic Title Valenzano, Dario R. Dr. Riemer, Jan Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/55725