Modulation of the Aging Process by the Release of Neuroendocrine Signals from Dense-Core Vesicles
2013 new Scholar Award in aging
Hormonal signals released by neurons affect our moods, emotions, and appetites. As a consequence, mood disorders such as schizophrenia and depression, and metabolic disorders such as obesity and diabetes can be caused by defects in neuronal hormone release. Many of these disorders have an age-related onset, but it is not known whether an age-related decline in neuronal hormone release is a contributing factor. Additionally, aging of the organism as a whole is modulated by hormonal signals produced by neurons and other tissues. Neuronal hormones are released from a unique organelle, the dense-core vesicle. Despite the importance of hormonal signaling in aging and other biological processes, surprisingly little is known about how dense-core vesicles are formed and how hormones are packaged into these vesicles. Furthermore, few of the hormonal signals that modulate aging have been molecularly identified.
Using the nematode worm C. elegans, we have identified a number of molecules important for the packaging of hormones into dense-core vesicles. We will study how defects in this process affect aging of the organism. We will also determine whether the release of hormones from dense-core vesicles declines during normal aging and during the progression of neurodegenerative diseases, and thus could be a contributing factor to the age-related decline in neuronal function. Finally, we will identify neurons that release hormonal signals that modulate aging, as a step towards identifying the hormones themselves.