Grant: CIHR Fellowship

Normal and disease-related aging involve molecular changes that occur within our cells. As proteins carry out most cellular activities, maintaining functional proteins is important for healthy aging. In contrast, many age-related diseases are characterized by disruption of cellular proteins. Transfer RNAs (tRNAs) are the molecules that decode the genetic message to assemble amino acids into proteins. My previous work demonstrated that some human genomes contain mutations in tRNA genes that have the potential to lead to mis-made proteins and contribute to disease. However, the impact of these mutant tRNAs on the aging process is not known. My proposed research is based on the hypothesis that mutations in tRNAs impact healthy aging by disrupting the functional proteins within cells. There are two aims to my work. In Aim 1, I will identify mutant tRNAs that alter cellular lifespan and determine properties of these tRNAs that explain their impact. In Aim 2, I will use mass spectrometry-based proteomics to identify how cellular proteins are affected by mutant tRNAs at various stages of the aging process. My work will uncover a novel link between mutations in tRNA genes and cellular aging, identify molecular changes that occur within cells as they age in the presence of mutant tRNAs and highlight cellular proteins and pathways that can be targeted by therapies to treat age-related diseases and promote healthy aging.