Speaker
Description
Space flight affects the human body in a way that is similar to physiological ageing [Demontis et al., 2017]. The fish Notobranchius furzeri (N. furzeri) is a suitable and consolidated model for ageing because of its very short, accelerated life cycle (three-four months, the shortest known to date for a vertebrate), characterised by the expression of a large number of vertebrate ageing markers [Cellerino et al., 2016]. Its genome has been sequenced; genome editing and transgenesis are possible [Harel et al., 2016]. Therefore, N. furzeri represents a fundamental platform to quickly test, on the whole life cycle, the impact of environmental treatments and/or gene manipulations related to vertebrate ageing. However, although it could open up new, unexpected windows on the molecular genetics of physiological adaptation to long-term space-flight and space-associated ageing, N. furzeri never flew in space. Therefore, we proposed to characterise the adaptive response of N. furzeri to spaceflight, suggesting that 1) the permanence in space of N. furzeri larvae is compatible with their survival, although with some possible dysmorphism [Crawford-Young, 2006; Proshchina et al., 2021]; 2) senescence can be measured with histological and molecular techniques. Moreover, since the eye is particularly affected by spaceflight (a specific neuro-ocular syndrome linked to spaceflight (Spaceflight associated Neuro-Ocular Syndrome - SANS) exists [Lee et al., 2020]), we will particularly evaluate the eye after post-flight organogenesis.
Our project aligns with the most recent recommendations of the European Space Agency (ESA) in terms of goals of research on gravitational biology and physiology, and introduction of novel experimental models for human physiology.
We will send to space and bring back to Earth quiescent larvae prone to resume the developmental cycle under controlled laboratory conditions, where three objectives will be pursued:
a) Analysis of gene expression involved in ageing and DNA repair.
b) Assessment of cell proliferation, cellular senescence, DNA damage, and differentiation of retinal cell types.
c) Evaluation of the post-flight eye function.
Instead of the adult swimming fish, we propose to use larvae in diapause, a state in which the dormant embryos do not eat or swim, a fundamental advantage impossible with other vertebrate model systems. Upon return to Earth, larvae will be induced to exit diapause and proceed through development until adulthood, when they will be characterised molecularly, morphologically and reproductively.
We expect to identify 1) specific genes involved in space-flight-induced ageing/adaptation and DNA damage repair; 2) pathophysiological traits of the space-exposed eye.
Overall, the project will evaluate the effects of space travel on N. furzeri, a well-established model system for ageing studies. If successful, the project will provide important information on the correlation between long-term space travel and senescence in a new model, and will lay the foundations for the use of N. furzeri in space biology.