Negligible senescence

2009 senior Scholar Award in aging

In relatively long-lived organisms such as humans, the lifelong maintenance of vital tissues (skin, digestive track epithelium, olfactory neurons, blood) depends on the replacement of cells lost to wear and tear by freshly minted daughter cells from resident stem cell populations. However, as animals age, the rate of turnover outpaces the rate of replacement due to a progressive decrease in the ability of stem cells to divide. If stem cells were to be spared from aging, a steady state between cell turnover and cell proliferation could emerge in somatic tissues that would likely render tissues negligibly senescent. This solution to the problem of aging is practiced by planarians, which possess totipotent adult somatic stem cells. Unlike other invertebrate (flies and nematodes) and vertebrate (mice) model systems, the question to be addressed in planarians is not why stem cells age with time, but rather why and how stem cells are kept in a constant state of biological youthfulness. The recent sequencing and annotation of the planarian Schmidtea mediterranea genome, the high degree of gene homology between this animal and mammals, combined with the cellular and biological tools we have developed to interrogate their biology opens the door for functional studies on aging in these animals. We propose to uncover the molecules responsible for regulating the unmitigated self-renewal of planarian stem cells, with the aim of testing the universality of these findings in vertebrate model systems.
Alejandro Sanchez Alvarado PhD
University of Utah