Background and objectives. Growing evidence suggests that aging is a multi-dimensional process, which involves structural and functional alterations of cardio-vascular, neural, muscular, cognitive and motor systems. As an illustration, Active Healthy Aging, on the one hand, and Frailty, on the other hand, can be considered as opposite functional states of the neuro-musculo-behavioral system on the continuum of aging trajectory. However, the classical disciplinary subdivisions still persist in gerontology research. This is particularly detrimental for understanding whether, how, and why healthy active aging can be preserved, that is, how the transition from robustness to frailty can be delayed by the use of multi-modal training interventions. Moving beyond disciplinary frontiers, the Plastic-Age project gathers specialists in behavioral neurosciences, cognitive psychology, human and animal physiology, biomechanics, and biomedical sciences around a common (inter-disciplinary) theoretical framework, inspired from complexity theory and dynamical systems analysis. It aims at exploring the effects of fitness level and different training programs on the different functional subsystems and their interactions. To achieve this objective, Plastic-Age connects theory and experimentation in humans and animals. In human, cross-sectional and interventional studies will be carried out. With respect to the investigation of fitness level, Master athletes will be taken as a reference model of healthy active aging and will be compared with low and moderate fit older adults. With respect to the effects of training, Plastic-Age will explore the benefits of multi-modal training programs on the plasticity of the neuro-musculo-behavioral system. Animal studies will be carried out in complementarity with human experimentation. They will allow investigating multi-scale processes (i.e., from cellular to the behavioral level). The findings arising from this fundamental research program will be used in two directions that are included in the project’s agenda. First of all, findings will be used as proofs of concept for developing recommendations destined to practitioners and older adults (i.e., new types of training programs), as well as guidelines to develop a portable neuro-technology dedicated to the assessment of brain health and fitness in aged individuals. In addition, presumably, the identified brain markers of exercise-induced plasticity might be used as input for The Virtual Brain (TVB) for simulations.
Program and methods. A 3 years experimental program is proposed, including 4 work packages (WP). WP1 and WP2 target the effects of fitness level, whereas WP3 is dedicated to study the effects of different types of training programs in humans, and WP4 is dedicated to animal studies. Cardio-respiratory fitness, muscular capacities and cognitive performance of each participant will be systematically and extensively assessed. Motor paradigms (Fitts’ task and Force Control) will be used to assess cognitive-motor dedifferentiation, behavioral dynamics and the coordination between muscular and behavioral levels. ECG, EMG, EEG, fNIRS, VO2 consumption will be used to obtain multi-scale and multi-level outcomes measures. In the animal part, aged rodents and frail mice will follow different training programs, combining aerobic and muscular exercise. Structural, cellular and biochemical analyses will be conducted in addition to behavioral analyses. A fifth WP (WP5), programmed in the 3rd year will allow elaborating recommendations to practitioners, defining the general specifications of a portable neuro-technology, allowing to assess individually the effects of physical training at brain level. The impact of the results for the virtual brain project will be also discussed.
Expected socio-economic impact and added value for AMU. Due to the revolution of longevity, better understanding how age-related declines in the multiple functional systems can be attenuated to preserve healthy active aging may have an important positive impact on the burden of health care systems. Plastic-Age will be a significant step in this direction, with the originality of: i) connecting complementary human and animal studies in an interdisciplinary research, and ii) investigating a continuum of functional states going from frailty (in animals) to Master athletes. Moreover, Plastic-Age will constitute a theoretically grounded foundation for clinical applications and for innovative technologies in the domains of aging and physical activity. Specifically, it will be providing guidelines regarding physical activity in elderly, and a proof of concept for developing a portable neuro-technology. It is also expected to enrich the link between empirical data and TVB platform developed within AMU at the Institut des Neurosciences des Systèmes, thereby extending its scope to the plasticity induced by exercise in the aging brain. As a result, the present project will enhance the regional, national and international positioning of AMU as a prominent player in the domain of research and innovation for healthy active aging, which is a growing field in the silver economy.