Grant: Travel Awards - Institute Community Support

We typically think that we age because our bodies cannot withstand the wear and tear of time. Recent studies challenge this passive aging paradigm suggesting that metabolic pathways involved in energy production play an active role in how we age. Houtkouper et al. (Nature 2013) demonstrated that mitochondrial ribosomal proteins (MRPs) play a central role in the aging process. MRPs are protein subunits of the mitochondrial ribosome, which is responsible for translating genes into functional molecules in our mitochondria. The mitochondria are cell organelles that are best known for producing energy, and so MRP activity within the mitochondria directly affects energy production within cells. Reduced levels of MRPs in a roundworm introduced mitochondrial stress, which invoked a biochemical stress response. The roundworm adapted to this metabolic stress by prolonging its lifespan and delaying age-related muscle deterioration. We do not know how MRPs are biochemically controlled in mammals, nor do we understand their role in how mammals age. We hypothesize that MRPs in mammals are controlled by normal physiological processes and that reducing their levels may affect metabolic health and lifespan. To better understand the function of MRPs, we are characterizing a new mouse model with reduced levels of a specific MRP, called MRPL54. We have compared mice with reduced levels of MRPL54 to mice with normal levels in a metabolic health analysis and a longevity study. Metabolic health outcomes in Mrpl54 HET compared to control WT mice were assessed using a series of metabolic health tests in young and aged mice to determine energy homeostasis, glucose metabolism, muscle function, lipid balance, response to cold exposure, and body composition. Most deaths in Canada result from age-related diseases. We hope that this study will help us better understand the aging process so that we can develop approaches to prevent age-related conditions and promote healthy aging.