We have developed molecular approaches to rejuvenating cells, counteracting specific mechanisms of aging.
Targeting key aging-related nodes in regulatory networks
The important roles of regulatory networks in controlling cell fate make them attractive targets for rejuvenating cells. We used a small molecule inhibitor of p38alpha MAPK to expand and rejuvenate aged muscle stem cells (MuSCs), enhancing their ability to repair and restore strength to damaged muscle.
We have pioneered a method for extending telomeres using modified mRNA encoding telomerase reverse transcriptase (TERT). The approach has several advantages: it is transient, non-immunogenic, and avoids risk of insertional mutagenesis. Shortened telomeres are causally linked to major age-related and genetic diseases including heart disease, diabetes, vascular dementia and, as discovered in our lab, Duchenne muscular dystrophy (DMD). We are extending telomeres in diverse cell types including MuSCs. Through diverse collaborations, we are translating these advances toward the clinic.