Grant: CIHR Fellowship

Aging is a progression of deterioration that leads to increased susceptibility to disease and eventually death. Despite the complexities of this deterioration, certain signals acting within a subset of the body's tissues have been found to significantly affect the rate of aging, causing a dramatic extension of lifespan of model organisms. Importantly, it is possible to extend the proportion of life spent healthy, and delay the onset of aging-associated diseases. One of the key aspects of aging which I wish to focus on is reproductive aging, since reproductive decline (i.e. the onset of menopause, in women) is one of the earliest hallmarks of aging in many organisms. Most of the genes of the roundworm C. elegans have similar functions to the equivalent human genes, but since this roundworm is short-lived and easily genetically altered or mutated, it is an ideal model for comprehensively studying complex, whole-life processes. I intend to use C. elegans to better understand a protein called CREB, in order to determine how CREB sends signals throughout the body that coordinate major events such as metabolic energy storage, lifespan, and reproductive aging. My preliminary experiments have shown that genetic mutations that reduce the levels of CREB lead to a delay in the reproductive decline of C. elegans, which is a newly discovered role for CREB. I will carry out an additional series of experiments to allow me to determine: 1) how CREB is affecting reproduction; 2) if CREB also has related effects on fat storage and lifespan; 3) where in the body (i.e. in which tissue) CREB's presence is necessary for these effects; and 4) what are the important signals or targets of CREB that allow it to alter such vital whole-body processes as reproductive aging. These studies will provide a clearer picture of how CREB operates, and potentially uncover new targets that can be manipulated to delay reproductive decline with aging.