Irina Conboy

The lack of tissue repair that eventually leads to the loss of organ function is an undeniable and devastating trait of aging that causes many degenerative disorders, exemplified by Parkinson’s, Alzheimer’s and muscle atrophy. One intriguing possibility is that stem cells residing in aged organs retain their intrinsic ability to regenerate but are not properly triggered in the aged environment and that rejuvenation of the aged niches is actually required for the efficient capacity for organ repair by not only endogenous, but also by transplanted young-embryonic stem cells. Our most recent work suggests that it is not simply the lack of “positive” systemic factors that causes a decreased regeneration with age. In contrast, we provide evidence that aged systemic and local organ niches dominantly inhibit the regenerative potential of all cell subsets within developmental lineage: embryonic stem cells, tissue-specific progenitor cells and entirely differentiated tissue containing a resource of dedicated precursors. These results strongly suggest that in order to optimally capture the tremendous organogenic potential of embryonic stem cells and their progeny, it is necessary to understand the molecular nature of the inhibitory components typical of aged niches and to design molecular devices enabling functional neutralization of such age-related inhibitors.