When we discuss the effect of aging on stem cell populations, we invariably lament the decrease in stem cell number and proliferative capacity that occurs in late life. It’s therefore newsworthy when anyone observes an age-related increase in stem cell populations — and this is just the case in the Drosophila midgut, where intestinal stem cells (ISCs) become more numerous with age. From Choi et al.:
Age-related changes in Drosophila midgut are associated with PVF2, a PDGF/VEGF-like growth factor
Age-associated changes in stem cell populations have been implicated in age-related diseases, including cancer. However, little is known about the underlying molecular mechanisms that link aging to the modulation of adult stem cell populations. Drosophila midgut is an excellent model system for the study of stem cell renewal and aging. Herein, we describe an age-related increase in the number and activity of intestinal stem cells (ISCs) and progenitor cells in Drosophila midgut. We determined that oxidative stress, induced by paraquat treatment or loss of catalase function, mimicked the changes associated with aging in the midgut. Furthermore, we discovered an age-related increase in the expression of PVF2, a Drosophila homologue of human PDGF/VEGF, which was associated with and required for the age-related changes in midgut ISCs and progenitor cell populations. Taken together, our findings suggest that PDGF/VEGF may play a central role in age-related changes in ISCs and progenitor cell populations, which may contribute to aging and the development of cancer stem cells.
To my knowledge, this is the first report of any stem cell compartment expanding with age in the fly. In the gonad, the situation is quite reversed, with germ line stem cells diminishing over the lifespan. Nonetheless, there are similarities: in the intestine, we see another case where intercellular signaling between stem cells and theirniche playing a critical role in determining the age-related changes in a stem cell compartment. In the gonad, the key factors were cadherins and unpaired signaling; in the intestine, the PDGF/VEGF homolog is essential.
The authors speculate that the expansion of the stem cell compartment in late life could result in the appearance of cancer stem cells. I would agree. Especially given the ability of oxidative DNA damage to mimic the effects of age in this system, the phenomenon might be less analogous to beneficial regeneration and more analogous to pre-cancerous hyperplasia. The obvious question, then: Do flies lacking the PGDF/VEGF homolog develop fewer intestinal tumors?