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A 2018 UPDATE ON THE STATE OF SEDENTARY BEHAVIOR SCIENCE

By Ken Smith, Senior Research Scholar and Director, Mobility Division, and Dr. Mary Rosenberger, Researcher, Stanford Center on Longevity

Introduction
In the spring of 2010, the Stanford Center on Longevity convened a group of the world’s leading scientists in the area of sedentary behavior science. At the time, a new wave of health research aiming to quantify the health risks of extended periods of sitting was emerging simultaneously in Australia and the U.S.  These researchers had ample evidence that long periods of sitting resulted in increased risk of negative health outcomes, and found a direct relationship between the length of uninterrupted sitting and the likelihood of precipitating a negative metabolic cycle.1,2 Dr. Marc Hamilton from the Pennington Research Center presented additional data from animal studies showing that increased sedentary time results in a decrease in the healthy enzyme activity that assists in fat metabolism, a potential direct link between sedentary behavior and obesity. 3,4 The group reached a consensus that the science had reached a state where extended sitting could be declared a health risk separate and independent from lack of exercise, although it was too early to resolve the question “how much is too much?” and what the definitive casual mechanisms might be. The press picked up these results and soon declared that “sitting is the new smoking,” a quote famously repeated by CEO Tim Cook at the launch of the Apple Watch. 
 
In May of 2018, the Baker Institute (an independent research institute located in Melbourne) and the University of Minnesota brought many of the scientists from the 2010 event back together, along with a number of new voices focused on sedentary research. The meeting served to update the state of sedentary behavior science, as well as promote discussion about unanswered questions and future directions for the field. Dr. Mary Rosenberger represented the Stanford Center on Longevity at this meeting, which focused on three areas:
 
• The physiological pathways affected by prolonged sitting
• Measurement techniques for researchers investigating sitting
• Intervention strategies to decrease sitting time
 
This whitepaper broadly summarizes the results of the 2018 meeting, as well as providing background references for scientific claims for those looking to delve deeper into a particular area.
 
Physiological Mechanisms of Sedentary Behavior
Understanding of the underlying causal mechanisms that make sedentary behavior bad for health have progressed significantly since 2010. At the time, the main evidence available in humans showed only that extreme sedentariness, such as extended bed rest, has an extremely negative effect on healthy metabolism.5
 
Newer studies using improved measurement methods have expanded the research to show that impaired blood flow,6 individual negative metabolic pathways,7,8 and genetic markers (data not yet published) are all affected negatively by prolonged sitting. What is emerging is that it is a chain reaction of slowed physiological processes caused by sitting that impairs health. Together, these mechanisms all play a role in increased risk for a number of chronic diseases, including stroke, dementia, diabetes, renal disease, and peripheral artery disease.9
 
The proposed sedentary path to diabetes is based on the body’s ability to regulate insulin during long periods of sitting. Decreased metabolic function begins with a decrease in the number and intensity of muscle contractions which normally occur when we engage the muscles10 we use to support our body weight in maintaining good posture as we stand and move about. This results in a decrease in both sugar and fat uptake from the blood flowing through those muscles.  Increased glucose and fatty acids in the blood stimulate normal processes to bring levels back to normal, but these rely on working muscles, and without movement, the processes can be ineffective.7 With this primary mechanism for clearing the blood not doing its job, the secondary system, introduction of insulin into the blood, can be overtaxed.11 This can be the start of a disordered metabolism, which can eventually result in a diabetic response to blood sugar. When prolonged sitting becomes a long term lifestyle, the accumulation of these metabolic deficits could prove to be a key factor in the increased risk of diabetes that comes with aging. 
 
A second potential pathway to negative sedentary effects is vascular, as function of the blood vessels is tightly linked to metabolic function. The reduction in muscular contractions described in the diabetic pathway above also slows the overall demand for oxygen in the muscles. This decrease in demand, along with a reduction in blood pressure in the legs in sitting vs. standing, reduces the amount and the velocity of the blood flowing through the capillaries of the large muscles in the legs. This, in turn, reduces the shear stress in the smaller blood vessels, which is key to endothelial function.12 The endothelium is made up of the cells that line the insides of blood vessels. These cells perform much of the oxygen exchange between the blood and muscles, as well as regulating a host of functions such as maintaining vascular tone, They also release a number of necessary regulating chemicals into the blood, such as leukocyte adhesions, which are a preliminary way of forming blood clots. Reduction in endothelial function is linked to a number of diseases, including arteriosclerosis.13,14
 
The final proposed pathway is genetic. Our bodies depend on gene expression for healthy regeneration of cells. Exposure to a great number of things can change the way genes are expressed. Although this pathway is not fully understood, prolonged sedentary behavior has so far been linked to the expression of approximately 500 different individual genes.15
 
Measurement of Sedentary Behavior
Accurate measurement of sedentary behavior is important is two ways. First, good sedentary science relies on these measurements for studies that will eventually answer questions about how long people can sit before incurring negative physical effects, and just what they need to do to break up these periods of inactivity. (e.g. Is just standing up enough?) Second, building sedentary measurement capability into widely used wearable devices is key to individuals self-monitoring their behavior and making lifestyle modifications. This is especially important in light of new scientific methods that can handle the vast amounts of data generated by wearables and identify patterns and recommendations at the individual level.
 
Since 2010, the bulk of progress has been in the wearable space, motivated in part by the inability of most questionnaires to accurately quantify sitting. Many devices now on the market provide some measure of sedentary time. Both Fitbit and Apple Watch now regularly send reminders to move and track sedentary time through the day. What is still missing, however, are solid recommendations on how long a person can comfortably sit without negative health effects. Because of this, the state of health messaging around sitting is extremely inconsistent. For now, each device maker interprets the science in their own way and makes their best estimate of how to set limits and alarms. This situation should improve as better devices and more research combine to create a virtuous cycle that improves our overall understanding of sedentary behavior mechanisms and limits, which will in turn inform the development of even better devices.
 
Intervention Strategies for Sedentary Behavior
Baker Institute scientists have dedicated a significant amount of work into developing and evaluating interventions that address the problem of sitting in occupational, entertainment, and transportation settings. These interventions can be delivered through interpersonal messaging, environmental design, behavioral modification platforms, or policy interventions.16 
 
While the majority of the Baker work has focused on work-related sitting, the interventions can be applied in other settings. For example, while up to 60% of Americans report meeting physical activity guidelines, this drops to 20% in those age 75 or older.17 Reducing sedentary behavior in this population might be extremely important in decreasing disease risk. In a study looking at the contribution of light activity in older adults, mortality was decreased in a group that was characterized as only “lightly active.”18 Additionally, getting exercise contributes twice to healthy aging; first by offsetting some of the time that might otherwise be sedentary during the day, but also conferring additional health benefits of cardiovascular-type activity.19 In older adults, walking was comparable to vigorous exercise in cardiovascular disease risk reduction.20
 
Conclusions and Future Directions
Since 2010, sedentary behavior science has advanced to become a well-recognized branch of physiology research and new studies are uncovering the underlying mechanisms that drive negative health outcomes. Efforts have also been made to integrate sitting into an overall picture of physical activity and to understand how it interacts with traditional views on exercise.
 
For example, new evidence has shown that while prolonged sitting can increase disease risk even in those who get recommended amounts of exercise, exercise does seem to confer a protective effect against some of the negative effects.21 Ideally, daily activities would always include both exercise and limited amounts of sitting for a healthy aging plan.
 
Continuing improvement in the capability and cost of wearable devices will undoubtedly contribute to better answers to questions around sedentary behavior, as well as how sleep, exercise and sedentary behavior interact to contribute to health outcomes. Many scientists are now studying sedentary behavior as part of a 24-hour model, which has also under exploration at the Stanford Center on Longevity.22 This activity-recovery-sedentary daily cycle seems to be the future of sedentary science as well as healthy aging.
 
The fact that sitting behaviors are an integral part of daily life makes identification of science-based recommendations challenging. Despite this, it is clear that the average individual can lead a healthier lifestyle by:
 
• Being physically active for at least 30 minutes a day (walking counts)
• Regularly interrupting sitting time with light activity or standing if possible.
 
Further improvements in population-level sitting behavior can be made through a combination of individual interventions, environmental design changes, and corporate or community policy. The Stanford Center on Longevity will continue to follow the development of sedentary behavior science and look for opportunities to influence better health behaviors.
 

Citations

1 Owen N, Bauman A, Brown W. Too much sitting: a novel and important predictor of chronic disease risk? Br J Sports Med [Internet]. 2009 Feb 1 [cited 2018 Jun 29];43(2):81–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19050003

2 Healy GN, Dunstan DW, Salmon J, Cerin E, Shaw JE, Zimmet PZ, et al. Breaks in sedentary time: beneficial associations with metabolic risk. Diabetes Care [Internet]. 2008 Apr 1 [cited 2018 Jun 29];31(4):661–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1825290

3 Hamilton MT, Hamilton DG, Zderic TW. Exercise physiology versus inactivity physiology: an essential concept for understanding lipoprotein lipase regulation. Exerc Sport Sci Rev [Internet]. 2004 Oct [cited 2018 Jan 10];32(4):161–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15604935

4 Hamilton MT, Healy GN, Dunstan DW, Zderic TW, Owen N. Too Little Exercise and Too Much Sitting: Inactivity Physiology and the Need for New Recommendations on Sedentary Behavior. Curr Cardiovasc Risk Rep. 2008 Jul;2(4):292–8.

5 Pavy-Le Traon A, Heer M, Narici M V., Rittweger J, Vernikos J. From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006). Eur J Appl Physiol [Internet]. 2007 Aug 21 [cited 2018 Jun 29];101(2):143–94. Available from: http://link.springer.com/10.1007/s00421-007-0474-z

6 Restaino RM, Holwerda SW, Credeur DP, Fadel PJ, Padilla J. Impact of prolonged sitting on lower and upper limb micro- and macrovascular dilator function. Exp Physiol [Internet]. 2015 Jul 1 [cited 2018 Jun 29];100(7):829–38. Available from: http://doi.wiley.com/10.1113/EP085238

7 Grace MS, Dempsey PC, Sethi P, Mundra PA, Mellett NA, Weir JM, et al. Breaking Up Prolonged Sitting Alters the Postprandial Plasma Lipidomic Profile of Adults With Type 2 Diabetes. J Clin Endocrinol Metab [Internet]. 2017 Jun 1 [cited 2018 Jun 29];102(6):1991–9. Available from: https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2016-3926

8 Dunstan DW, Kingwell BA, Larsen R, Healy GN, Cerin E, Hamilton MT, et al. Breaking up prolonged sitting reduces postprandial glucose and insulin responses. Diabetes Care [Internet]. 2012 May 1 [cited 2018 Jun 29];35(5):976–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22374636

9 Owen N, Healy GN, Matthews CE, Dunstan DW. Too much sitting: the population health science of sedentary behavior. Exerc Sport Sci Rev [Internet]. 2010 Jul [cited 2018 Jan 10];38(3):105–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20577058

10 Healy GN, Dunstan DW, Salmon J, Cerin E, Shaw JE, Zimmet PZ, et al. Objectively measured light-intensity physical activity is independently associated with 2-h plasma glucose. Diabetes Care. 2007;30:1384–9.

11 Bergouignan A, Latouche C, Heywood S, Grace MS, Reddy-Luthmoodoo M, Natoli AK, et al. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials. Sci Rep [Internet]. 2016 Oct 24 [cited 2018 Jul 2];6(1):32044. Available from: http://www.nature.com/articles/srep32044

12 Thosar SS, Johnson BD, Johnston JD, Wallace JP. Sitting and endothelial dysfunction: the role of shear stress. Med Sci Monit [Internet]. 2012 Dec [cited 2018 Jul 2];18(12):RA173-80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23197245

13 Maruhashi, T; Kihara, Y; Higashi, Y (2018). “Assessment of endothelium-independent vasodilation: From methodology to clinical perspectives”. Journal of Hypertension: 1. doi:10.1097/HJH.0000000000001750.

14 Eren E, Yilmaz N, Aydin O (2013). “Functionally defective high-density lipoprotein and paraoxonase: a couple for endothelial dysfunction in atherosclerosis”. Cholesterol. 2013: 792090. doi:10.1155/2013/792090

15 Latouche C, Jowett JBM, Carey AL, Bertovic DA, Owen N, Dunstan DW, et al. Effects of breaking up prolonged sitting on skeletal muscle gene expression. J Appl Physiol [Internet]. 2013 Feb 15 [cited 2018 Jul 2];114(4):453–60. Available from: http://www.physiology.org/doi/10.1152/japplphysiol.00978.2012

16 Thorp AA, Owen N, Neuhaus M, Dunstan DW. Sedentary Behaviors and Subsequent Health Outcomes in Adults: A Systematic Review of Longitudinal Studies, 1996–2011. Am J Prev Med [Internet]. 2011 Aug 1 [cited 2018 Jan 11];41(2):207–15. Available from: http://www.sciencedirect.com/science/article/pii/S0749379711003126

17 Lee I-M, Shiroma EJ. Using accelerometers to measure physical activity in large-scale epidemiological studies: issues and challenges. Br J Sport Med. 2014;48(3):197–201.

18 Chastin SFM, Palarea-Albaladejo J, Dontje ML, Skelton DA. Combined Effects of Time Spent in Physical Activity, Sedentary Behaviors and Sleep on Obesity and Cardio-Metabolic Health Markers: A Novel Compositional Data Analysis Approach. PLoS One. 2015;10(10).

19 Copeland JL, Ashe MC, Biddle SJ, Brown WJ, Buman MP, Chastin S, et al. Sedentary time in older adults: a critical review of measurement, associations with health, and interventions. Br J Sports Med [Internet]. 2017 Nov 1 [cited 2018 Jul 2];51(21):1539. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28724714

20 Manson JE, Greenland P, LaCroix AZ, Stefanick ML, Mouton CP, Oberman A, et al. Walking Compared with Vigorous Exercise for the Prevention of Cardiovascular Events in Women. N Engl J Med [Internet]. 2002 Sep 5 [cited 2018 Jul 2];347(10):716–25. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa021067

21 Schmid D, Ricci C, Leitzmann MF. Associations of objectively assessed physical activity and sedentary time with all-cause mortality in US adults: the NHANES study. PLoS One. 2015/03/15. 2015;10(3):e0119591.

22 Smith K, Rosenberger M. Keeping Seniors Active – A 24-Hour Approach [Internet]. Stanford, CA; 2017. Available from: https://longevity.stanford.edu/blog/2017/08/11/keeping-seniors-active-a-24-hour-approach/

 
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