Information: This scholarship is funded by Universitas Padjadjaran - Indonesia
Subject Areas: Biomedical Sciences
Project Title: Elaborating Role of Hippo Pathway Effectors YAP and TAZ and their association with skeletal muscle ageing
Project Supervisor: dr. Ronny, M.Kes., AIFO., Ph.D
The United Nations Population Fund have predicted that by 2035, the number of people aged 60 or above in Indonesia will reach 15% or twice the level in 2010.1 Increasing population age have wide implications both economically and also in the healthcare sector. Old age is associated with significant comorbidities such as degenerative and cardiovascular diseases. Additionally, the loss in muscle mass further decreases their quality of life.2 Equipped with this knowledge, an intervention must be developed to deal with this looming problem. One well known intervention to improve the quality of life in the aging population is exercise.
Exercise is defined as a form of structured and regular physical activity3 and has been known to improve the aging process.4 Exercise exerts its effect through the regulation of metabolisms, inflammations, and the immune system. Several possible mediators of exercise effects are through myokines, autophagy, and the Hippo signalling pathway. Myokines are cytokines secreted by the skeletal muscle in association with exercises.5 Several myokines have already been identified with interleukin 6 being the first identified myokines which is implicated in the regulation of muscle hypertrophy.6 The Hippo pathway are also associated with organ size regulation. The effector of the pathway, Yes-associated protein (YAP) and its homologue transcriptional coactivator with PDZ-binding motif (TAZ) are implicated in increased muscle size.7,8 Autophagy is another important effector of the effects of exercise. Although at first seemed counterintuitive, autophagy helps maintain cellular homeostasis and in fact are associated with the prevention of aging.9 Therefore, these pathways involvement in muscular hypertrophy may reverse the loss of muscle mass associated with aging.
Several different types of exercise intensity have been characterized according to the lactate threshold. Our research team have established the lactate threshold model of exercise intensity in rats10 and have conducted preliminary studies exploring the association of different exercise intensity and processes associated with aging. Several processes that we have explored are the effects of different exercise intensity on autophagy in skeletal muscles11, cardiac muscle12,13, and hepatic tissues14. Using this data, we are trying to expand our research on aged mice to see whether these responses is modified by aging itself.
Other aspects that we’re also trying to explore is the regulation of absorption of different nutrients in old age. The common metabolic diseases such as dyslipidaemia and diabetes are highly associated with age. Several research have associated the degeneration of the gastrointestinal tracts with impaired nutrient absorption.15 In this project we are also planning to evaluate whether exercise can improve the effects whether through alterations in cellular signals in the gut or other pathways.
By understanding the pathways implicated in muscle size regulations and changes in the aging processes, several potential therapeutic avenues are revealed. Finding the optimal exercise intensity which provide the greatest benefit while minimizing the risk associated with exercise is essential. Additionally, by understanding the pathway involved in exercise that influences muscle size, we may also exploit and influence these pathways with exogenous substances or supplements and alter or prevent skeletal muscle aging.