The Interactions Between Aging, Circadian Rhythm, and Cancer Risk
This open access review paper outlines what is known of the way in which aging, circadian rhythm, and cancer risk interact with one another. Cancer is a well known as an age-related disease; among other contributing mechanisms, the mutation burden in somatic cells increases with age, while the surveillance conducted by the immune system, intended to destroy cancerous cells long before they form a tumor, declines with age. Separately, circadian rhythm regulation also becomes dysfunctional with advancing age, though the causative mechanisms in this case are little understood in comparison to what is known of the causes of cancer. Lastly, circadian rhythm interacts with cancer risk in potentially complex ways, again an area in which more research is needed before we might be able to say it is well understood.
Cancer, circadian rhythms, and aging are three biological processes closely associated with health and disease. While they may appear to be independent, increasing evidence suggests that there are complex interactions among them. The relationship between aging and cancer is very clear. Aging remains to represent the foremost risk factor across various cancer types, correlating with an elevated incidence of cancer that typically reaches its peak around the age of 85 years. On the mechanism, aging and cancer share many common hallmarks, including genomic instability, epigenetic alterations, chronic inflammation, cellular senescence, and so on, which serve as intermediaries between aging and cancer.
Circadian rhythms are 24-hour cycles that govern a range of physiological processes in living organisms, such as sleep-wake cycles, hormone release, metabolism, and cell proliferation. Disruption of circadian rhythms has also been shown to contribute importantly to the development and progression of cancers, although the exact mechanisms are not yet fully understood. Mechanistically, circadian rhythm proteins exhibit physical interactions with molecules implicated in cancer-related pathways, thus exerting influence over cancer initiation and progression.
Furthermore, there also exist complex and multifaceted relationships between aging and circadian rhythms. On the one hand, the aging process reduces the resilience of circadian rhythms, resulting in disrupted sleep-wake cycles, a diminished ability to synchronize circadian rhythms in peripheral tissues, and changes in the molecular functioning of circadian clock outputs. On the other hand, circadian rhythm dysfunction can accelerate the aging process by compromising essential bodily functions. These disruptions lead to increased oxidative stress, which refers to cellular damage caused by an imbalance between the production of reactive oxygen species (ROS) and the cell's ability to neutralize them. This imbalance of ROS can lead to DNA damage, protein denaturation, and lipid peroxidation, ultimately contributing to inflammation and the development of age-related health issues