Understanding biological responses to environmental fluctuations (e.g. heatwaves) is a critical goal in ecology. Biological responses (e.g. survival) are usually measured with respect to different time reference frames, i.e. at specific chronological times (e.g. at specific dates) or biological times (e.g. at reproduction). Measuring responses on the biological frame is central to understand how environmental fluctuation modifies fitness and population persistence. We use a framework, based on partial differential equations (PDEs) to explore how responses to the time scale and magnitude of fluctuations in environmental variables (= drivers) depend on the choice of reference frame. The PDEs and simulations enabled us to identify different components, responsible for the phenological and eco-physiological effects of each driver on the response. The PDEs also highlight the conditions when the choice of reference frame affects the sensitivity of the response to a driver and the type of join effect of two drivers (additive or interactive) on the response. Experiments highlighted the importance of studying how environmental fluctuations affect biological time keeping mechanisms, to develop mechanistic models. Our main result, that the effect of the environmental fluctuations on the response depends on the scale used to measure time, applies to both field and laboratory conditions. In addition, our approach, applied to experimental conditions, can helps us quantify how biological time mediates the response of organisms to environmental fluctuations.