mechanisms underpinning the age-dependent proprioceptive decline

During aging in human, joints, tendons and skin deteriorate both morphologically and functionally, resulting in a progressive physiological abnormality in proprioception. C. elegans also processes proprioception, which enables its rhythmic sinusoidal movement, and its proprioceptive system shares molecular and functional similarities with humans, such as mechanoreceptors in proprioceptive tissues and crosstalk between various tissues for motor regulation. In C. elegans, the mechanosensation in interneurons, motor neurons and body wall muscle cells, as well as sensory integration among these cells cumulatively contributes to proprioception. Any age-related changes in these components will induce proprioceptive deterioration. Identification of mechanosensors in different tissues, characteristic of the neural circuits of proprioception, and demonstration of an aging effect on proprioceptive constituents in C. elegans will provide insights into the proprioceptive dysfunction with age. Our preliminary results show that stretching animals’ body induces inward currents in both body wall muscle cells and motor neurons. Intriguingly, stretch-induced electrical signals in different tissues exhibit no functional decay until late-life, even though C. elegans displays alternation in locomotion patterns from mid-life. We hypothesize that different proprioceptive components display distinct age-dependent decay rates and that longevity genes play important roles in regulating age-related decline in proprioception. Since mechanosensors play a key role in proprioception for organisms, the project will utilize a candidate RNAi screening to identify mechanosensitive channels in muscle cells and motor neurons. Furthermore, the project will employ a multidisciplinary approach to elucidate the poorly understood interactions among various proprioceptive tissues. Moreover, the project will investigate how aging affects the activity of membrane-associated mechanoreceptors as well as the interactions between motor neurons and body wall muscle cells. Lastly, since proprioception in C. elegans is modulated by biogenic amine neurotransmitters, such as dopamine and serotonin, the age-related changes in neurotransmitter levels may contribute to the functional deterioration of proprioception. Therefore, we will examine neurotransmitter release in dopaminergic and serotoninergic neurons, as well as their effect on C. elegans proprioception with age.