Influence of age and diabesity on bedrest/microgravity-induced functional decline and upon recovery in mice

• Grant number: 22/02596-7
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: August 08, 2022
• End date: February 07, 2023
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: José Rodrigo Pauli
• Grantee: Renan Fudoli Lins Vieira
• Supervisor: Amandine Chaix
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: University of Utah (U), United States
• Associated to the scholarship: 20/14320-0 - Effects of physical exercise on KLF15 protein and regulation of hepatic gluconeogenesis in hyperglycemic mice, BP.MS

Abstract

The current climate crisis has been sharply exerting global pressure to alter patterns of action and accelerate profound changes in pursuit of sustainable urban systems. Within this scenario, the community of scholars in sustainability transitions has sought approaches that enable path-deviating advances in socio-technical systems, especially at the urban scale. However, understanding and applying such theories in the local Brazilian context, where both the field of territorial planning and the discussions on systemic change are still emerging, can be considered a challenge. The notion of urban transformative capacity developed by Wolfram (2016; 2019) identifies the skills necessary for cities and stakeholders to forward changes toward sustainability, preparing and facilitating transition processes. The aim of the research is, on the theoretical side, to deepen the knowledge about the methodological approach to urban transformative capacity and, on the practical side, to apply it in a German case study that directly contributes to the analysis of Brazilian cases (Santo André and Mauá). The research will be based on a literature review, document analysis, and technical visits with key actors of the German transition processes. It is intended to articulate new approaches - such as urban transformative capacity, socio-technical transition theory, and the Brazilian spatial planning field - to analyze urban infrastructures, in particular in the context of drainage and stormwater management. Research into the concepts of urban transformative capacity and urban transitions is given a high prominence by the Leibniz Institute of Ecological Urban and Regional Development (IOER), given that among its research areas one of them stands out, "Research Area of Transformative Capacities". Besides that, The IOER has cooperation with various faculties of the University of Excellence for supporting the academic education of students. Thus, the institute's teaching services focus on Dresden Leibniz Graduate School (DLGS) with a course on Urban Transformative Capacity being offered in the winter semester at the TU Dresden. Prof. Dr. Marc Wolfram designed the concept of urban transformative capacity at IOER, the institution where he is the director, and he has a high experience in understanding complex socio-technical systems and sustainability transitions. In addition, the professor is co-founder of the STRN thematic group "Urban transitions and transformations", which can open doors and opportunities for possible cooperation, publications, and other scientific activities. (AU) Heart and immune functions, muscle mass and strength, and bone density are examples of physiological parameters and functions that decline with aging, further exacerbated by obesity and metabolic disease condition. With the concomitant increase in the prevalence of older and obese individuals, delineating the mechanisms driving accelerated diet and aging-induced frailty and identifying therapeutic countermeasures is an imperative to improve the quality of life and alleviate the economic burden associated with unhealthy aging in a large fraction of the near future population. Less applicable to the mass at first sight, yet economically relevant and with unknown potential costly long-term health consequences, is the possibility of spaceflights to become accessible to the layman in the not so far future. Time-restricted feeding (TRF) is a new diet intervention that limits food consumption to an 8- 10h window daily without overt changes in diet quality or quantity. In rodents, TRF prevents and reverses diet-induced obesity (DIO) and associated metabolic dysfunction. Preliminary results from an ongoing study suggest that TRF can delay age-associated physiological decline, in particular improving heart and immune function. Whether TRF could be used to accelerate functional recovery after bedrest or microgravity experience is unknown. Our long-term goal is to shed light on the mechanisms behind age/obesity/spaceflight - associated decline in bodily functions in order to develop new preventative and/or recovery strategies. Specifically, this project will capitalize on a well-established mouse model of bedrest and microgravity to characterize the effect of aging, microgravity and western diet feeding on a spectrum of physiological functions during immobilization and/or spaceflight and during the recovery. We hypothesize that age and obesity exacerbates the physiological impairments associated with bedrest/microgravity and that dietary manipulations such as time-restricted feeding can facilitate physiological recovery. We will test this hypothesis in the following aims: Aim 1: Characterize the effect of aging and diabesity on the deleterious effects of cardiovascular deconditioning, skeletomuscular disuse and immune alterations induced by mechanical hindlimb unloading in male mice. Aim 2: Determine whether and how TRF can promote cardiac, muscle and bone recovery following disuse atrophy. (AU)