Disrupted body clocks raise risk of early death, study finds

By Priyanjana Pramanik, MSc.Reviewed by Susha Cheriyedath, M.Sc.Apr 29 2025

Middle-aged adults with disrupted circadian rhythms face a heightened risk of death from cardiovascular, kidney, and metabolic diseases, new evidence suggests early lifestyle interventions could save lives.

Study: Circadian syndrome and mortality risk in adults aged ≥ 40 years: a prospective cohort analysis of CHARLS and NHANES. Image Credit: vetre / Shutterstock

In a recent article published in the journal Scientific Reports, researchers utilized data from the United States and China to investigate the relationships between a cluster of behavioral and metabolic disruptions, known as the Circadian Syndrome (CircS), and cause-specific and all-cause mortality among middle-aged to older adults.

Their findings indicate that CircS is significantly correlated with mortality attributed to cardiovascular, cerebrovascular, kidney disease, diabetes, malignant neoplasms, Alzheimer’s disease, certain infections, and death from all causes. The research team also found evidence of a graded association, with mortality risk rising progressively with the number of CircS components observed. While a graded increase in mortality risk was observed with more CircS components, the linear trend was borderline significant (p = 0.06), and no non-linear pattern was detected.

Cause-specific mortality data were only available for the U.S. cohort; such data were not collected in the Chinese cohort.

Background

Circadian rhythms are the near-24-hour biological cycles present in nearly all living organisms. In mammals, they are regulated by the brain's suprachiasmatic nucleus, a small region located in the hypothalamus. This nucleus regulates key functions, including thirst and hunger, as well as sleep.

These rhythms influence essential physiological processes such as sleep-waking cycles, metabolism, and immune function. However, modern lifestyles – characterized by shift work, excessive exposure to light, and irregular sleep patterns – have increasingly disrupted these rhythms.

Circadian disruption affects a significant portion of the American population, including shift workers and those working indoors. Disruptions in circadian rhythms have been linked to a wide range of health issues, including neurodegenerative, cardiovascular, metabolic, and immune disorders.

Research shows that circadian misalignment contributes to conditions like Alzheimer’s disease, type 2 diabetes, and cardiovascular disease. This has led to the development of CircS as a concept, which extends the traditional Metabolic Syndrome by including depressive symptoms and sleep deprivation.

While individual components of CircS, such as depression, sleep deprivation, and metabolic risk factors, are known to increase mortality, the collective impact of CircS on mortality has not been fully explored.

About the study

Researchers aimed to address an important research gap by examining the relationship between CircS and mortality outcomes among middle-aged to older adults, using data from large, nationally representative surveys in the United States and China.

Participants under 40 or lacking essential data related to sleep, metabolic, depression scores, or follow-up were excluded. After filtering, 7,637 Chinese respondents and 9,320 American participants remained.

People were considered to have CircS if they reported at least four out of seven components, namely hypertriglyceridemia, central obesity, low high-density lipoprotein (HDL) cholesterol, hypertension, hyperglycemia, sleep deprivation (defined as less than six hours), and depressive symptoms.

Mortality follow-up for the Chinese population used death records and interviews, with an average follow-up of 8.26 years. The American mortality data were obtained from the United States National Death Index, with a mean follow-up of 7.4 years.

Cox proportional hazard models with three levels of covariate adjustment and Bayesian generalized linear models were used to assess associations between CircS and all-cause or cause-specific mortality. Additional analyses included Kaplan-Meier survival curves and restricted cubic splines for dose-response assessment.

Findings

Of the 7,637 participants in the Chinese survey, 2,270 had CircS; 4,335 respondents out of 9,320 in the American study had the condition. In both cohorts, people with CircS were older and had higher rates of chronic diseases, including heart disease, hypertension, and diabetes.

Over a 9.17-year follow-up for the Chinese cohort, 142 deaths occurred, with mortality rates higher in the CircS group (2.9 compared to 2.0 per 1,000 person-years). In the American cohort, over a mean of 7.4 years, 1,321 deaths were recorded, with higher mortality in the CircS group (18.56 compared to 10.90 per 1,000).

Adjusted models confirmed that CircS significantly increased mortality risk, with a hazard ratio of 1.79 for the Chinese and 1.21 for the American cohorts. For American respondents, the association was especially pronounced for adults between 40 and 60.

Key CircS components like large waist circumference, depression, diabetes, and hypertension were individually linked to increased mortality. In the American cohort, CircS was significantly associated with multiple specific causes of death, including heart disease, diabetes, kidney disease, Alzheimer’s disease, malignant neoplasms, and infections such as influenza and pneumonia.

In adjusted models, CircS was associated with particularly high mortality risk from diabetes (HR 6.81) and kidney disease (HR 2.49) in the U.S. cohort. These estimates were derived from Bayesian-adjusted models with very narrow highest density intervals (HDIs), a feature that reflects model precision but may warrant cautious interpretation.

Conclusions

This study is the first to show a strong, consistent association between CircS and both all-cause and cause-specific mortality in large, diverse cohorts.

CircS likely disrupts biological functions performed by vascular, inflammatory, metabolic, and other systems, increasing vulnerability to chronic diseases and premature death. Notably, mortality risk was highest among individuals between 40 and 60 with CircS.

This study's strengths include using two well-established cohorts with diverse populations and long follow-ups. However, inferences are limited by the reliance on self-reported data, lack of physical activity and nutrition covariates, and the absence of cause-specific mortality data from the Chinese cohort.

In conclusion, CircS is a modifiable cluster of risk factors linked to increased mortality. Early detection and lifestyle interventions targeting CircS components could significantly reduce disease burden and mortality in middle-aged and older adults.