BACKGROUND: The mammalian circadian clock and its associated clock genes are 
increasingly been recognized as critical components for a number of 
physiological and disease processes that extend beyond hormone release, thermal 
regulation, and sleep-wake cycles. New evidence suggests that clinical behavior 
disruptions that involve prolonged shift work and even space travel may 
negatively impact circadian rhythm and lead to multi-system disease.
METHODS: In light of the significant role circadian rhythm can hold over the 
body's normal physiology as well as disease processes, we examined and discussed 
the impact circadian rhythm and clock genes hold over lifespan, 
neurodegenerative disorders, and tumorigenesis.
RESULTS: In experimental models, lifespan is significantly reduced with the 
introduction of arrhythmic mutants and leads to an increase in oxidative stress 
exposure. Interestingly, patients with Alzheimer's disease and Parkinson's 
disease may suffer disease onset or progression as a result of alterations in 
the DNA methylation of clock genes as well as prolonged pharmacological 
treatment for these disorders that may lead to impairment of circadian rhythm 
function. Tumorigenesis also can occur with the loss of a maintained circadian 
rhythm and lead to an increased risk for nasopharyngeal carcinoma, breast 
cancer, and metastatic colorectal cancer. Interestingly, the circadian clock 
system relies upon the regulation of the critical pathways of autophagy, the 
mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and 
silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) 
(SIRT1) as well as proliferative mechanisms that involve the wingless pathway of 
Wnt/β-catenin pathway to foster cell survival during injury and block tumor cell 
growth.
CONCLUSION: Future targeting of the pathways of autophagy, mTOR, SIRT1, and Wnt 
that control mammalian circadian rhythm may hold the key for the development of 
novel and effective therapies against aging- related disorders, 
neurodegenerative disease, and tumorigenesis.