Giaquinto, Daniela (2024) The chemical senses of fish and mice: a journey into the biology of aging. [Tesi di dottorato]

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Abstract

Taste and smell, through the recognition of specific substances and molecules, are essential senses for survival and interaction with conspecifics across all living organisms. However, in course of aging the ability to discern tastes and smells can diminish or undergo significant alterations, potentially contributing to mortality. To obtain accurate and reproducible data on the chemical senses in aging, especially within basic and translational research, it is crucial to standardize the husbandry and management of laboratory animals. The first objective of this thesis was to establish a standardized husbandry protocol and primary procedures for Nothobranchius furzeri, the model organism in our facility ZeNoLab. The second objective was to morphologically characterize the taste and olfactory organs in adult N. furzeri. Finally, the third objective was to comparatively characterize the peripheral organs for taste and smell at both morphological and molecular levels during the aging of N. furzeri and Mus musculus. In the first paper of this collection, we utilized the accumulated expertise within our ZeNolab facility, working with eggs, embryos, larvae and adult animals of N. furzeri strain MZM. We developed husbandry techniques and key experimental procedures for this species. For the second paper, we conducted morphological and immunohistochemical characterization of the olfactory epithelium and peripheral gustatory apparatus in adult N. furzeri. In the third paper, we used N. furzeri (MZM strain) at three age points (2, 6, and 12 months) and the CD-1 strain of Mus musculus at 6, 12, and 18 months. Both represent outbred strains within their species. The selected age points correspond to the onset of sexual maturity, adulthood and old stages in both species. We conducted in vivo investigations, behavioral tests assessing taste and olfaction, as well as ex vivo molecular and immunohistochemical analyses to observe structural and functional changes consistent with behavioural observations. We successfully defined a husbandry protocol and procedural guidelines for N. furzeri, which have been implemented in our facility and submitted to a leading journal in the field. We characterized the chemical senses in N. furzeri, resulting in the publication of our second paper in the collection. In our third paper, we observed significant behavioral and structural changes in both species with aging and we draw meaningful conclusions on common age-related mechanisms of chemosensory decay in vertebrates. In conclusion, this thesis and the papers within it serve as a valuable resource for researchers interested in N. furzeri as a model organism, as well as a comprehensive exploration of the chemical senses across the evolutionary scale, with comparative and translational insights.

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