Impacts of aging on the entrainment capability of the mammalian circadian system

Abstract The circadian system of mammals is composed of a hierarchical network of oscillators, including a core clock and peripheral clocks. The core clock receives an external photic signal and transmits it to the peripheral clocks, which, in turn, feed back to the core clock. Aging affects various functions of organisms including the circadian system. Entrainment displays the adaptability of the circadian system to changes in the external environment. However, there is currently no systematic study on the effects of aging on the entrainment capability. To explore the influencing mechanism, we develop a mathematical model of two populations of Goodwin oscillators, which represent the core clock and peripheral clocks. Based on numerical simulations, we conduct a detailed study on the impact of three aging-related factors on the entrainment capability represented by the entrainment range, entrainment time, and entrainment phase. The results indicate that the decrease in the sensitivity of suprachiasmatic nucleus (SCN) to light and the coupling strength from the SCN to the peripheral clocks due to aging increase the phase difference between the core and peripheral clocks, narrow the entrainment range, and prolong the entrainment time. A reduction in the coupling strength within the SCN has little effect on the three aspects mentioned above but increases the entrainment phase. Overall, aging reduces the circadian system’s adaptability to the external environment, and the increased entrainment phase may lead to corresponding sleep problems. We also show that modulating the internal coupling strength in the peripheral clocks can mitigate aging effects; this provides an idea for using peripheral clocks to adjust the core clock, while also revealing new insights into the interaction between aging and the elasticity of the circadian system. This mechanism provides theoretical support for treating or alleviating circadian system disorders or sleep problems caused by aging.