Climate change is characterized by global surface warming associated with the anthropogenic increase in greenhouse gas concentrations since the start of the industrial era. In the Earth’s upper atmosphere where many modern technologies reside, it is now recognized that a long-term cooling has been taking place over the past several solar cycles. Compelling evidence for such cooling comes from direct measurements of the thermospheric density and the ionospheric temperature. A lot more indirect evidence has become available since the 1990s following a seminal modeling study by Roble and Dickinson (1989), suggesting potential effects of increased greenhouse gases on the ionosphere and thermosphere. However, there are several outstanding issues, for example, (1) the very strong ionospheric cooling observed by multiple ionospheric radars that does not fit with the prevailing theory based on the argument of anthropogenic greenhouse gas increases; (2) CO2 trends in the mesopause region observed by satellite missions are about twice of what current general circulation models predict; (3) trends in atmospheric wave activity and their impacts on the atmosphere-ionosphere system are poorly known and unquantified. Our international team will be taking on these challenging outstanding topics as our research theme, with the goal to improve the understanding of the long-term trends in the ionosphere and thermosphere.