This $651,793 federal Project Grant award from the National Institute on Aging's Aging Research program (CFDA 93.866) supports research at the University of California, San Diego to investigate translation fidelity and proteostasis in hematopoietic stem cells (HSCs) across the aging process. The key products and services to be delivered under this 5-year award include:
Quantifying relative translation fidelity in young adult vs. aged HSCs and progenitor cells using a novel single-cell assay, and determining the impacts of increased protein synthesis on translation fidelity in HSCs.
Evaluating if enhancing translation fidelity through a genetic mouse model (RPS23K60R) can delay or mitigate age-related declines in HSC function, stem cell exhaustion, and organismal lifespan.
Assessing the effects of enhanced translation fidelity on proteostasis and proteotoxic stress response pathways in HSCs over the lifespan.
These studies aim to elucidate the role of cell-type-specific translation fidelity in conferring stem cell longevity and identify potential therapeutic strategies to enhance stem cell fitness and extend human healthspan by preventing age-related proteostasis disruption.