UC Irvine

Menopause is one of the earliest age related declines in humans. Uncovering factors that influence reproductive aging is of interest with regard to human reproductive health, and is also an important first step in understanding the overall aging process. The Caenorhabditis elegans hermaphrodite germline has been established as a highly-suitable model system, but many questions remain regarding the factors that modulate its aging.

Although IF is well known to extend lifespan in a variety of species including C. elegans, less is known about its effect on reproductive aging. I show that IF can delay worm reproductive cessation without reducing brood size. As a first step in establishing means to understand the ways in which IF exerts its effects on reproductive aging, I characterize germline changes that occur as reproductive activity is modulated; I chose this approach because reproductive aging is likely to be linked to reproductive activity and to germline stem cell (GSC) activity. Specifically, I find that GSCs of individuals with low reproduction rates randomly occupy a dormant state in which they do not cycle. I also show that increasing reproduction rate alters germline compartment makeup, which occurs independently of oocyte fertilization. A strong candidate for regulation of at least some of these responses is the stem cell niche provided by the distal tip cell (DTC). Indeed, niche architecture has been hypothesized to play an important role in stem cell regulation. The DTC extends processes whose functional significance is unknown. Using time-lapse imaging, I show this growth to be an active and highly-dynamic process. This suggests that process growth may be an important component of the regulation of GSC behavior.

Overall, I report striking, novel behaviors of the C. elegans reproductive system as a whole, and of GSCs in particular. I also report a new intervention by which reproductive cessation can be delayed without sacrificing brood size. This lays the foundation for future studies to identify the underlying causes of reproductive aging, and to identify ways in which this aging is intrinsically controlled and can be further manipulated by external intervention.