Aging is characterized by progressive decline in physiological functions with increasing chronological ages. Among all the age-dependent declines, loss of motor function represents one of the most prominent physiological declines in aging animals and humans. Our previous work has shown that motor neurons exhibit a progressive functional decline in the early life of C. elegans, while skeleton muscles remain functional until mid to late life. Here, we report that arecoline, a muscarinic acetylcholine receptor agonist can improve the age-dependent functional loss of the motor nervous system and significantly increase the lifespan of the animals. There are three different muscarinic acetylcholine receptors in worms, GAR-1, -2, -3. When we applied arecoline to these three muscarinic acetylcholine receptor mutants, we found that arecoline failed to extend only the lifespan of gar-2 mutants, but not the other two. Therefore, this suggests that GAR-2 receptor, which is participated in the Gq signaling, might mediates the effect of arecoline on lifespan extension. Furthermore, egl-8 (PLCβ), a downstream effector of Gq signals is also required for arecoline treatment to extend lifespan, suggesting that arecoline-induced lifespan extension may mediate through GAR-2/PLCβ pathway. Finally, we found that the over-expression of gar-2 only in motor neuron is sufficient to rescue the arecoline-induced lifespan extension in gar-2 mutants, suggesting that arecoline-induced lifespan extension acts specifically in motor neuron. Our findings have implicated a potential way to mitigate the age-dependent decline in motor activity. Further investigating the mechanism of action may eventually lead to the development of interventions that can increase both the heath span and the lifespan of humans.