Molecular Connections Between Circadian Clocks and Aging

The mammalian circadian clockwork has evolved as a timing system that allows the daily environmental changes to be anticipated so that behavior and tissue physiology can be adjusted accordingly. The circadian clock synchronizes the function of all cells within tissues in order to temporally separate preclusive and potentially harmful physiologic processes and to establish a coherent temporal organismal physiology. Thus, the proper functioning of the circadian clockwork is essential for maintaining cellular and tissue homeostasis. Importantly, aging reduces the robustness of the circadian clock, resulting in disturbed sleep–wake cycles, a lowered capacity to synchronize circadian rhythms in peripheral tissues, and reprogramming of the circadian clock output at the molecular function levels. These circadian clock–dependent behavioral and molecular changes in turn further accelerate the process of aging. Here we review the current knowledge about how aging affects the circadian clock, how the functional decline of the circadian clock affects aging, and how the circadian clock machinery and the molecular processes that underlie aging are intertwined.