Sleep-wake cycle, aging and cancer

Abstract

Disruptions in sleep-wake patterns have been linked to a variety of health problems, including an increase risk for obesity, type II diabetes, and hypertension. The link to increased risk of malignancy and premature aging is less clear, however. This manuscript reviews current epidemiological and experimental evidence linking alterations in sleep-wake patterns to malignancy and premature aging. Epidemiological evidence suggests that alterations in sleep-wake patterns (e.g.; night-shift or rotating-shift work) are associated with increases in leukemia, endometrial, breast, prostate, and colorectal cancers. Excessive long or short sleep duration is associated with increased mortality. These observations are further supported by experimental animal model systems: Sleep deprivation causes death in Drosophila cycle01 mutants. Manipulations of light-dark cycle in rodents or mutations that knock out certain genes in the circadian pathway accelerate aging and neoplastic growth. Melatonin, the pineal hormonal signal of darkness appears to have evolved in part to protect against mutagenesis by synchronizing cellular proliferation, differentiation, and apoptosis to the cireadian peaks and troughs of genotoxic stress. A model based on circadian-gating of sleep-wake cycles, therefore, links the circadian pathway to the mutational theories of senescence and neoplasia.