The INSPIRE animal cohort will eventually include 1,5760 mice and be one of the 3 largest animal cohorts on aging in the World with the National Institute on Aging’s (Baltimore, USA) and Calico’s (Google in California, US). Research on this mice cohort will be complemented by a specific fish model, the Nothobranchius furzeri or African Killifish and a an original dog cohort in real life conditions.
1. Murine cohort (non-consanguineous SWISS mice)
This murine animal research cohort is hosted at the Functional exploration & experimental resources regional Centre (CREFRE – US006 / Inserm – UT3 Paul Sabatier), under the responsibility of Pr. Angelo Parini (I2MC) and Bruno Guiard and Sébastien Lopez (CRCA-CBI). It is intended to be a mirror cohort of the human cohort in order to put into perspective the results of translational research found in humans and vice versa, on models of aging animals and living under risky conditions such as humans (sedentary lifestyle, hyperlipidic diet). The main objectives of the animal cohort are as follows:
- To determine the evolution over time of frailty / accelerated aging induced by specific risk factors (sedentary lifestyle, inactivity, overweight and obesity).
- To correlate functional frailty to markers of aging / senescence
- To identify new biomarkers and pharmacological targets to prevent & treat frailty or accelerated aging.
To this end, decision was made to work on relatively young human and animal cohorts, but with several frailty/accelerated aging risk factors, such as sedentary lifestyle, overweight and obesity. By extrapolation, we can consider that this animal cohort would correspond to a human population of individuals aged between 30 and 70 years.
As in humans, blood, urine, stool will also be collected.
In addition, the behavioral phenotyping of the mice cohort will be conducted by the Mouse Behavioral Core platform from the Integrative Biology Centre (http://cbi-toulouse.fr/fr/equipe-mouse-behavioral-core) under the responsibility of Drs Lopez, Guiard and Rampon.
2. Fish model : African Kilifish
Alongside the murine cohort, the INSPIRE project will also be based on the use of a fish model presenting with accelerated aging, hosted at the STROMALab under Cédric Dray’s and Jean-Philippe Pradère’s supervision. The Nothobranchuis Furzeri, more commonly known as the African Kilifish, is one of the vertebrates with the shortest lifespan. The rapid mode of reproduction of this animal, due to environmental conditions, causes it to develop accelerated aging (4 to 6 months) of all its organs, comparable to that observed in humans.
This characteristics makes this fish an essential study model for identifying and validating new hypotheses within the INSPIRE project. Thus, through experiences of physical exercise, fasting and re-feeding or targeted nutritional challenge, the African Kilifish model will enable, in a short time, the reproduction of the various stresses targeted by the INSPIRE project. These animals will be phenotyped in order to better apprehend their locomotor and cognitive abilities (videotracking) but also to understand the contribution to accelerated aging of isolated mechanisms in humans in terms of metabolism and immune and regenerative capacities.
3. Canine cohort in real life conditions
The canine cohort should be seen at the Ecole Nationale Vétérinaire de Toulouse, under the responsibility of Pr. Isabelle Raymond Letron, in association with STROMALab, that took the initiative, at the instigation of Pr. Louis Casteilla.
The originality of the canine cohort lies in its complementarity and synergy with the human translational research cohort on the one hand and the animal model cohorts (mice and fish) on the other. Dogs are animals with a physiology close to that of man and they present a comparable aging process. Many physical and behavioral aging signs are found in humans and dogs, as well as the observation of many age-related diseases of the same nature (cancer, metabolic diseases, osteoarthritis, neurodegenerative diseases, etc.). They fully share their masters’ environment (air, water, food, exposure to potential contaminants, etc.), and very often their lifestyle (active or sedentary).
An additional advantage of the canine model is its rapid aging since its average lifespan is much less than that of its owners and is very variable according to the breeds considered. Finally, the scientific and technological level of veterinary medicine makes it possible to evaluate the biological and physical parameters of dogs in a way almost identical to that of humans (physical and clinical examination, blood and urine analyses, medical imaging, functional tests, etc.).
The cohort will extend from adulthood to older animals without age limit, and will be recruited, clinically explored and followed in a manner as similar as possible to the human translational research cohort, to generate a broad platform of bio resources and canine data reflecting the human platform. The primary objective of the studies carried out will be to identify markers of biological aging, markers of age-related diseases or frailty of relevant individuals in dogs and transposable to humans and to understand the mechanisms and determinisms of biological aging.
