Several factors could explain the positive association between time spent sitting and higher all-cause death rates. First, time spent sitting might be more easily measured than physical activity and/or may reflect a different aspect of inactivity than other indices usually used in epidemiologic studies. However, this potential misclassification of exposure is unlikely to fully explain our findings, because time spent sitting was significantly associated with mortality even among men and women with the highest levels of physical activity.

Second, time spent sitting might be associated with other unhealthy behaviors that are either not captured or incompletely captured through questionnaires. Total energy expenditure is reduced among individuals who are sedentary. However, consistent with previous studies, the present study found no correlation between physical activity and time spent sitting (r = –0.03). Time spent sitting is also associated with greater food consumption and subsequent weight gain, especially when watching television (16, 34, 35). Time spent sitting was previously shown to be associated with increased weight gain in this cohort (18). While residual confounding by obesity could contribute to the association between sitting time and mortality, this association was attenuated but not eliminated by controlling for or stratifying on body mass index.

Third, prolonged time spent sitting, independent of physical activity, has important metabolic consequences that may influence specific biomarkers (such as triglycerides, high density lipoprotein cholesterol, fasting plasma glucose, resting blood pressure, and leptin) of obesity and cardiovascular and other chronic diseases (8–11). Animal studies have also shown that sedentary time substantially suppresses enzymes centrally involved in lipid metabolism within skeletal muscle, and low levels of daily life activity are sufficient to improve enzyme activity (36–38). Furthermore, substantial evidence in both adults and children from observational studies and randomized clinical trials shows that reducing time spent sitting lowers the risk of obesity and type II diabetes (19, 39–42).

We excluded sequentially from this analysis men and women who reported a personal history of cancer (n = 21,785), heart attack (n = 11,560), stroke (n = 2,513), or emphysema/other lung disease (n = 9,321) at the time of enrollment. We also excluded individuals with missing data on physical activity (n = 4,240), missing sitting time (n = 2,954), missing or extreme (top and bottom 0.1%) values of body mass index (n = 2,121), or missing smoking status (n = 1,347) at baseline. Finally, to reduce the possibility of undiagnosed serious illness at baseline that would preclude or interfere with physical activity, we excluded individuals who reported both no daily life activities and no light housekeeping (n = 4,730), as well as those who died from any cause within the first year of follow-up (n = 403). After exclusions, the analytical cohort consisted of 123,216 individuals (53,440 men and 69,776 women) with a mean age of 63.6 (standard deviation, 6.0) years in men and 61.9 (standard deviation, 6.5) years in women when enrolled in the study in 1992.

We examined the association between time spent sitting and total mortality in men and women combined, stratified by body mass index (Table 3). Although time spent sitting and physical activity were more strongly associated with mortality among lean persons (for time spent sitting, P_interaction = 0.06; for physical activity, P_interaction = 0.002), both measures were significantly associated with risk of total mortality regardless of body mass index.