The ageing of the population represents a major public health challenge. According to the WHO, the world’s population aged over 60 is expected to reach 2 billion by 2050, compared to 900 million in 2015. The growth of ageing populations brings with it an increase in health costs, as older people are more likely to develop chronic diseases with multiple morbidities, which are more expensive to treat.
In this context, the INSPIRE programme aims to develop an integrative vision of biological ageing with the aim of promoting healthy ageing. INSPIRE is a research programme that aims to build a platform of bio-resources from animal to human, from cell to individual, and from research to clinical care. Thus, this programme is based on the creation of a human cohort (made up of approximately 1,000 subjects, men and women, aged 20 years or more), an animal cohort (mice and fish), and the implementation of the ICOPE programme for seniors in Occitania in conjunction with the WHO [1-4].
I2MC is involved in several axes
of the INSPIRE project
Under the responsibility of Prof. Angelo Parini, Yohan Santin coordinates all the steps of creation, implementation and characterization of the INSPIRE mouse cohort, up to the sample collection and the constitution of the biobank. He also ensures the connection between the different researchers/laboratories in Toulouse who are involved in the project. In parallel, he is involved in research activities aimed at developing new therapeutic strategies to limit the cardiotoxic side effects of certain anti-cancer treatments.
Yohan Santin obtained his PhD in pharmacology from the University Paul Sabatier, Toulouse, France, in 2019. His work aimed to understand the role of mitochondrial oxidative stress in the development of post-infarction heart failure.
Areas of expertise
Aging, Senescence, Oxidative stress, Mitochondrial function, Autophagy
PhD, Inserm Researcher
PhD in Molecular, Cellular and Integrated Pathophysiology, supervisor A Hovnanian (2009); Post-Doc Laboratory of L. Iruela-Arispe, UCLA, USA (2010-2015); Since 2016, CRCN INSERM Team Bouloumié, I2MC, Toulouse.
Main domains of expertise
Vascular biology, cell biology, endothelial cells, adipose tissue, inflammation, aging, senescence.
Jeanne Mialet-Perez is working in the field of cardiac aging and age-associated diseases. She is specialized in the effects of oxidative stress-mediated signaling pathways of cardiomyocytes such as autophagy, apoptosis and senescence. She contributed to a better understanding of the role of mitochondrial enzymes monoamine oxidases in cardiac diseases.
Jeanne Mialet-Perez received her PhD in Endocrinology at the University of Paris, France, in 2002. After a post-doctoral experience at the University of Cincinnati, (Ohio, USA) in 2002-2005 in “genetic of cardiovascular diseases”, she joined the institute I2MC of Toulouse where she was recruited as a research associate at INSERM.
Main domains of expertise
Oxidative stress, Mitochondrial function, Autophagy, Aging, senescence.
Engineer in biological experimentation and instrumentation
Under the direction of Prof. Angelo Parini, Yosra Doghri is in charge of the cardiovascular phenotyping of the animal cohort of the INSPIRE project and participates in the sample collection. She is also involved in the functional exploration of various internal projects of the institute.
Yosra Doghri obtained her degree in veterinary medicine in 2015 in Tunisia. She continued her studies at the Ecole Nationale Vétérinaire Agroalimentaire et de l’Alimentation in Nantes where she obtained her PhD in nutrition and metabolic pathologies.
Field of expertise
Cardiovascular physiology, metabolic pathologies, oxidative stress
Engineer in animal experimentation: vascular phenotyping in aged mice in a disturbed metabolic condition
Under the direction of Prof. Angelo Parini, Rana Zahreddine is responsible for the metabolic phenotyping of the animal cohort of the INSPIRE project. She is also involved in scientific projects within the I2MC by developing various vascular and metabolic exploration techniques. At the same time, she performs vascular and cardiac microsurgery techniques on mice.
Rana ZAHREDDINE obtained her bachelor’s degree in biology at the Lebanese University in 2013. She continued her graduate studies at Paul Sabatier University, Toulouse, where she obtained her master and doctorate in pathophysiology in 2020. Her thesis work focused on the agonistic effect of estrogen and estrogen receptor (ERα) on the arterial wall, with a particular interest on the selective modulation of ERα
Areas of expertise
Vascular and metabolic pathophysiology, in vivo microsurgery, endothelium, histology, microscopy and molecular biology.
Tél/phone:+33 (5) 31 22 40 89
Pilar OREJA FUENTES
Inspire mouse cohort
The creation of the INSPIRE murine cohort (one of the 3 largest animal cohorts on ageing in the world) is supervised by Angelo Parini (email@example.com), former director of the I2MC and current co-director of the teams “CERAMIC” . This cohort is intended to mirror the human cohort in order to put the results of translational research carried out in humans into perspective and vice versa. Thus, the 1576 non-inbred mice making up the cohort accumulate several human risk factors for frailty/accelerated ageing such as a sedentary lifestyle, overweight and obesity .
The main challenges of this cohort are to:
1. Determine the evolution over time of frailty/accelerated ageing induced by specific risk factors
2. Correlate functional frailty with markers of ageing (notably cellular senescence)
3. Identify new biological markers and pharmacological targets to prevent & treat frailty/accelerated ageing.
INSPIRE translational projects I2MC
I2MC is also developing research programmes in connection with INSPIRE around the same strategy: identifying nutritional interventions to prevent/limit cellular senescence and slow down multi-organ ageing. The teams involved in these projects therefore aim to
1/ evaluate the effects of “Time Restricted Feeding” and senolytics on the onset of frailty (coordinator Anaïs Briot: firstname.lastname@example.org),
2/ to determine the role of caloric restriction on chronic renal failure and the morphology of arterial endothelial cells during aging (coordinator Muriel Laffargue: email@example.com)
3/ to prevent premature multi-organ ageing by mitochondrial targeting via NAD+ supplementation (coordinator Jeanne Mialet-Perez: firstname.lastname@example.org).
The I2MC is also in close collaboration with the INSPIRE program thanks to the SPHERES project coordinated by Dominique Langin, current director of the I2MC (email@example.com). Funded by an ERC Synergy program, the SPHERES project aims to determine the role of the adipocyte lipid droplet in age-related cardiometabolic diseases. The INSPIRE mouse cohort thus offers a unique opportunity to study the impact of ageing, gender, exercise and obesity on the relationship between adipocyte size and cardiometabolic parameters. Together with the work in humans, the INSPIRE SPHERES joint program will link new insights into the formation and maintenance of GLs in hypertrophied adipocytes to the deleterious impact of adipocyte hypertrophy in the context of ageing.
THEY ARE SUPPORTING US
The Inspire Research Initiative: A Program for Geroscience and Healthy Aging Research Going from Animal Models to Humans and the Healthcare System. de Souto Barreto, P.; Guyonnet, S.; Ader, I.; Andrieu, S.; Casteilla, L.; Davezac, N.; Dray, C.; Fazilleau, N.; Gourdy, P.; Liblau, R.; et al.,J Frailty Aging 2020, doi:10.14283/jfa.2020.18 PubMed
The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort). Guyonnet, S.; Rolland, Y.; Takeda, C.; Ousset, P.-J.; Ader, I.; Davezac, N.; Dray, C.; Fazilleau, N.; Gourdy, P.; Liblau, R.; et al. .,J Frailty Aging 2020, 1–11, doi:10.14283/jfa.2020.38 PubMed
Integrated Care for Older People and the Implementation in the INSPIRE Care Cohort. Takeda, C.; Guyonnet, S.; Sumi, Y.; Vellas, B.; Araujo de Carvalho, I., J Prev Alzheimers Dis 2020, 7, 70–74, doi:10.14283/jpad.2020.8. PubMed
Towards a Large-Scale Assessment of the Relationship between Biological and Chronological Aging: The INSPIRE Mouse Cohort. Santin, Y.; Lopez, S.; Ader, I.; Andrieu, S.; Blanchard, N.; Carrière, A.; Casteilla, L.; Cousin, B.; Davezac, N.; De Souto Barreto, P.; et al. J Frailty Aging 2021, 10, 121–131, doi:10.14283/jfa.2020.43 PubMed
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