Using an interactive, bi-dimensional model of the middle atmosphere, we simulate the long-term changes of temperature and chemistry in the mesosphere during the second half of the twentieth century, taking into account the 11-year solar cycle, the increase of water vapor at the tropopause, and the anthropogenic increases of methane and carbon dioxide. It is found that the long-term increase of water vapor at stratopause levels results in a long-term decrease of mesospheric ozone, hence of solar heating. The long-term mesospheric cooling due to this new mechanism is maximum in the lower mesosphere, and has the same order of magnitude as the cooling due to CO2 increase.