The aging clock: circadian rhythms and later life

Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented.

Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.

Worldwide, the human population is graying rapidly: between 2010 and 2050, the proportion of adults over 65 years of age will double from 8% to 16% of the global population (1). Aging affects all aspects of our physiology and behaviors, including the circadian clock. Although the processes underlying aging are not well understood, increasing evidence suggests that the circadian system influences aging and longevity in important ways (23).

Circadian rhythms play a vital role in health, and prolonged disruptions to the clock are associated with negative health consequences. With increasing age, the circadian system undergoes significant changes that affect rhythms of behaviors, temperature regulation, and hormone release, to name only a few examples. Although many of these changes may be an inevitable part of development, others may perhaps represent the operation of pathological processes that simply correlate with age. Improved understanding of the distinction between these concepts may create valuable opportunities to intervene and improve quality of life. This is particularly important in light of mounting evidence that disrupted circadian rhythms are an early warning sign of developing neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s (35), and that the circadian clock is heavily implicated in the etiology of metabolic diseases, chronic inflammation, and cancers (69).

In this Review, we survey some of the key age-associated changes in circadian rhythms of behavior, physiology, and molecular processes. We then consider some of the central hypotheses of what underlies these changes, and summarize evidence for putative mechanisms of action.

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