February 4, 2015

Effects of Sedentary Lifestyle on Telomere Length

Could standing up have a greater effect on health than increasing exercise?
With all the focus on the health benefits of increasing exercise, we may be overlooking a more critical, and simple, way to improve health—standing up.


Sjögren P, Fisher R, Kallings L, Svenson U, Roos G, Hellénius ML. Stand up for health—avoiding sedentary behaviour might lengthen your telomeres: secondary outcomes from a physical activity RCT in older people. Br J Sports Med. 2014;48(19):1407-1409. 


Randomized, controlled physical activity intervention trial in elderly, obese individuals 


Of the 101 participants who took part in an earlier study on exercise and cardio-metabolic risk,1 data from 49 (14 men and 35 women) were randomly selected to be analyzed in this current study.  All of the study participants were overweight, had a sedentary lifestyle and had abdominal obesity. All were 68 years old at time of enrollment.

Study Medication and Dosage

Individuals in the study were randomly selected to participate in an individualized exercise training program on prescription. Physical activity was measured with a 7-day diary, questionnaires, and a pedometer. Sitting time was measured with the short version of The International Physical Activity Questionnaire.

Outcome Measures

Telomere length was measured in blood cells (qPCR assay on DNA extracted from whole blood samples) at baseline and 6 months. 

Key Findings

Time spent exercising—including moderate and low-intensity exercise—as well as steps taken per day increased significantly in the intervention group. Reported sitting time decreased in both groups. In the initial study, positive changes were seen in several cardiovascular risk factors in both groups, but particularly in the intervention group.  
No significant associations between changes in steps per day and changes in telomere length were noted. In the intervention group, there was a nonsignificant trend toward shorter telomeres that correlated with increased time spent exercising (rho=‒0.39, P=.07). This trend was also seen in the control group (rho= ‒0.39, P=.08). The only parameter that was statistically significant was reduction in time spent sitting in the intervention group. In this group, telomere lengthening was significantly associated with reduced sitting time (rho=‒0.68, P=.02).

Practice Implications

This recent study by Sjögren et al suggests there may be a problem with our current attitudes about how important a contributor exercise is to good health. Increasing exercise may be less important than we think. These results suggest that our real focus should be on reducing time spent sitting. Our modern sedentary behavior may be the real problem. Our assumption that short bouts of exercise that may keep us fit will also counter the harm from our days spent sitting may be erroneous. In fact, exercise bursts may do little to counter the effect of long periods of sitting. In fact, while further research is needed, this study suggests those exercise bursts may even make the situation worse.2
Taking a brief detour to gain a historical perspective may help put these results into a more comprehensible perspective. We take chairs for granted, but the reality is that chairs have only recently come into common usage. Chairs were invented centuries ago, but few people actually sat in them; they were reserved for only the highest-ranking individuals. Kings sat on thrones while everyone else stood. Chairs were a symbol of royalty and status, but they were not particularly comfortable. It wasn’t until the 16th century that chairs became commonplace, at least in well-to-do homes, so that common people had a chance to sit down. It has only been in the last century that a significant portion of the population has spent any length of their waking hours sitting in chairs. In the course of human evolution, this is a sudden, abrupt change in behavior to wchich we appear to be ill adapted.
When considered in evolutionary terms, humans have spent most of the past 2 million years expending a great deal of energy moving about in order to obtain the energy from nutrients required to survive. Some simple estimates suggest that we spend half the energy through physical activity as our ancestors did. This is expressed as energy expenditure/resting energy expenditure or Physical Activity Level (PAL) units. Hayes et al report that humans living in subsistence-level societies expend about 3.2 PAL per day compared to the 1.67 average expended in contemporary society.3
Another way to measure energy expenditure is by using a pedometer. Modern American men now average about 5,000 steps per day, while men living in Amish farming communities take about 3.5 times that, nearly 18,400 steps per day.4,5
The paradigm that moderate physical exertion, such as going to the gym or for a run, will promote good health may be wrong. Instead it may be that sedentary behavior, spending our days sitting and not expending energy, is the problem and anything that lowers this behavior pattern has benefit.6 In this current Sjögren paper, we should note that there was a nonsignificant trend toward shorter telomeres seen with increasing exercise in both the intervention and the control groups. This seems paradoxical to what we would expect.
Could we read these data to suggest that sitting makes us older instead of exercising making us younger? 
The scientific consensus about telomeres is still black and white; longer telomeres are good, shorter ones are bad. Short telomeres are considered the hallmark sign of aging.7
In an earlier paper appearing in this journal, Lise Alschuler ND, FABNO wrote:
Telomeres are protective caps on the end of chromosomes that confer genomic stability. With each cell division, the telomere is shortened, until ultimately reaching a length that destabilizes the chromosome. At this point, the cell dies. Systemically and over a lifespan, abnormal telomere shortening predicts risk for chronic diseases, namely cardiovascular disease and cancer. The opportunity to improve healthy longevity lies in preventing premature telomere shortening.8
Telomere length may be superior to other common biomarkers used in predicting cardiovascular disease risk. Haycock et al’s July 2014 meta-analysis published in the British Medical Journal included 24 studies involving 43,725 people. They divided the results into thirds, creating tertiles. The researchers found participants with the shortest telomere length (first tertile) vs those with the longest telomere length (third tertile) clearly had greater cardiovascular risk. The first tertile had 54% higher pooled risk of coronary heart disease vs the third tertile (relative risk [RR]=1.54; 95% confidence interval [CI]: 1.30-1.83) across all of the studies. The first tertile also had a 40% increased cardiovascular risk in perspective studies (RR=1.40 [1.15-1.70]) , and an 80% higher risk in retrospective studies (RR=1.80 (1.32-2.44).9 While not commonly used clinically, telomere length appears to reliably predict risk.
Repeated cell division is considered the primary mechanism behind shortening telomere length but other causes contribute—in particular chronic exposure to DNA-damaging agents such as ultraviolet light, oxidative stress, and inflammation. Physiological and psychological stress are also associated with decreased telomere length.10 So what explains this paradoxical finding that exercise may be associated with shorter telomeres in the current study?
Regular physical activity, including exercise training, reduces the risk of developing many age-related chronic diseases (eg, cardiovascular disease, certain cancers, type II diabetes),11 but the actual molecular basis of these benefits is not yet well understood. Considerable interest is focused on how exercise and other lifestyle interventions affect telomere length. While we want to assume that exercise either lengthens telomeres or at the least prevents shortening, research results have been mixed; a number of studies actually suggest extreme exercise shortens telomeres. Most research on telomere length has been done retrospectively on preserved DNA samples. Results from multiple studies have reported 1 of 3 relationships between telomere length and exercise: positive association, no-association, or an inverted U relationship. In this inverted U, both sedentary and extremely active individuals have shorter telomeres than moderately active individuals.12 As this current trial reported, increased exercise seemed to reduce telomere length.
In light of these results, one must ask whether we have been interpreting the data incorrectly. Studies that compare athletes with sedentary individuals have assumed that the exercise was responsible for perceived benefits. But perhaps being sedentary is what causes the shortening telomeres, and exercise is beneficial only because it decreases the amount of time spent sitting.
Some studies certainly report a positive association between physical activity and telomere length. Cherkas et al’s 2008 paper reported that increasing physical activity was associated with increased telomere lengths, equating to a 10-year decrease in biological age between active and inactive subjects.13 These differences are even more extreme in some studies: Ultramarathon runners compared to sedentary individuals have telomeres that suggest a 16-year difference in biological age.14 Active individuals have longer telomeres compared to sedentary individuals, but could these results not be restated to say sedentary individuals have shorter telomeres than active individuals whose lifestyles are closer to our evolutionary predecessors?15,16 Could we read these data to suggest that sitting makes us older instead of exercising making us younger? 
A few studies have reported an inverted U relationship between physical activity and telomere length, where moderately active individuals exhibit longer telomeres compared to both sedentary and extremely active individuals. In their 2008 paper, Ludlow et al showed that individuals in both the lowest and highest quartiles of exercise-specific energy expenditure had shorter telomeres than individuals in the second quartile—even when controlling for age, gender, and body weight.17
In 2012, van del Ploeg et al, reported an association of "sitting time" with all-cause mortality in a large cohort of Australians. Using prospective questionnaire data from 222,497 individuals 45 years or older and with nearly 3 years of follow-up, the researchers reported that all-cause mortality hazard ratio was 1.40 (1.27-1.55) for individuals who spent 11 or more hours per day sitting: “The association between sitting and all-cause mortality appeared consistent across the sexes, age groups, body mass index categories, and physical activity levels and across healthy participants compared with participants with preexisting cardiovascular disease or diabetes mellitus."18
Sedentary behavior is associated with increased cancer risk. An August 2014 meta-analysis, which combined data from 17 prospective studies to include a total of 857,581 participants, suggested that sedentary behavior increased overall risk of cancer by about 20% (RR=1.20, 95% CI: 1.12-1.28). This effect varied between cancer types, with endometrial and lung having the largest significant increases in relative risk (RR=1.28 and 1.27, respectively).19
In a 2010 meta-analysis, Friedenreich reported that sedentary behavior was a significant etiologic factor in breast cancer. In 73 studies that provided adequate data for review, the average reduction in breast cancer risk when comparing the most to least physically active women was 25%. The strongest associations were found for moderate-intensity exercise, including both recreational and household activities, sustained over a lifetime.20
If you spend a considerable portion of your workday sitting with patients and then spend evenings reading journal articles, these are troubling findings. It is difficult to acknowledge that a basic element of one’s lifestyle has such a negative impact on health. This current study suggests that our attempts at short periods of rigorous exercise, while they may keep us fit, do little to counter the overall effect of a sedentary life. A quick workout at the gym may even make things worse.
Thus we need not only to find ways to reduce our own sedentary behaviors but also to find ways to model such behavior for our patients. Perhaps the easiest approaches may be to stand up and to use a pedometer. Standing while working takes a little getting used to, but it is an easy enough habit to form. Wearing pedometers to track physical activity has become commonplace. The commonly set goal of taking 10,000 steps per day is actually somewhat arbitrary, inherited from marketing efforts to sell pedometers in Japan and the creation of walking clubs as part of that effort in the 1960s.21 The number may have been chosen as a round number; it has become a frequent measure and goal to reach for22 and has become part of the definition of an active adult.23 It is easy enough to wear a pedometer to work and recommend them to patients. New technology makes them inexpensive enough. 

Categorized Under


1. Kallings LV, Sierra Johnson J, Fisher RM, et al. Beneficial effects of individualized physical activity on prescription on body composition and cardiometabolic risk factors: results from a randomized controlled trial. Eur J Cardiovasc Prev Rehabil. 2009;16(1):80-84.
2. Sjögren P, Fisher R, Kallings L, Svenson U, Roos G, Hellénius ML. Stand up for health—avoiding sedentary behaviour might lengthen your telomeres: secondary outcomes from a physical activity RCT in older people. Br J Sports Med. 2014;48(19):1407-1409. 
3. Hayes M, Chustek M, Heshka S, Wang Z, Pietrobelli A, Heymsfield SB. Low physical activity levels of modern Homo sapiens among free-ranging mammals. Int J Obes Relat Metab Disord. 2005;29:151-156.
4. Bassett DR, Schneider PL, Huntington GE. Physical activity in an Old Order Amish community. Med Sci Sports Exerc. 2004;36:79-85.
5. Bassett DR, Jr, Wyatt HR, Thompson H, Peters JC, Hill JO. Pedometer-measured physical activity and health behaviors in United States adults. Med Sci Sports Exerc. 2010;42(10):1819-1825.
6. Katzmarzyk PT. Physical activity, sedentary behavior, and health: paradigm paralysis or paradigm shift? Diabetes. 2010;59(11):2717-2725. Free full text.
7. López-Otín C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153(6):1194-1217.
8. Alschuler L. Optimal longevity hinges on telomeres. Nat Med J. 2013;5(6). Available at http://naturalmedicinejournal.com/journal/2013-06/optimal-longevity-hinges-telomeres. Accessed February 2, 2015.
9. Haycock PC, Heydon EE, Kaptoge S, Butterworth AS, Thompson A, Willeit P. Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2014;349:g4227. 
10. Ludlow AT, Ludlow LW, Roth SM. Do telomeres adapt to physiological stress? Exploring the effect of exercise on telomere length and telomere-related proteins. Biomed Res Int. 2013;2013:601368. Free full text.
11. Ludlow AT, Roth SM. Physical activity and telomere biology: exploring the link with aging-related disease prevention. Journal of Aging Research. 2011;2011790378.
12. Ludlow AT, Ludlow LW, Roth SM. Do telomeres adapt to physiological stress? Exploring the effect of exercise on telomere length and telomere-related proteins. Biomed Res Int. 2013;2013:601368. doi: Epub 2013 Dec 24. Free full text.
13. Cherkas LF, Hunkin JL, Kato BS, et al. The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008;168(2):154-158. 
14. J. Denham, C. P. Nelson, B. J. O’Brien et al. Longer leukocyte telomeres are associated with ultra-endurance exercise independent
of cardiovascular risk factors. PLoS ONE. 2013;8.
15. Du M, Prescott J, Kraft P, et al. Physical activity, sedentary behavior, and leukocyte telomere length women. Amer J Epidemiol. 2012;175(5):414-422. 
16. Kim JH, Ko JH, Lee DC, et al. Habitual physical exercise has beneficial effects on telomere length in postmenopausal women. Menopause. 2012;19(10):1109-1115. 
17. Ludlow AT, Zimmerman JB, Witkowski S, Hearn JW, Hatfield BD, Roth SM. Relationship between physical activity level, telomere length, and telomerase activity. Med Sci Sports Exerc. 2008;40(10):1764-1771.  
18. van der Ploeg HP1, Chey T, Korda RJ, Banks E, Bauman A. Sitting time and all-cause mortality risk in 222 497 Australian adults. Arch Intern Med. 2012;172(6):494-500. 
19. Shen D, Mao W, Liu T, et al. Sedentary behavior and incident cancer: a meta-analysis of prospective studies. PLoS One. 2014;9(8):e105709.
20. Friedenreich CM. The role of physical activity in breast cancer etiology. Semin Oncol. 2010;37(3):297-302.
21. Rettner R. The truth about '10,000 Steps' a day. Live Science Web site. http://www.livescience.com/43956-walking-10000-steps-healthy.html. Published March 7, 2014. Accessed February 2, 2015.
22. Tudor-Locke C, Bassett DR Jr. How many steps/day are enough? Preliminary pedometer indices for public health. Sports Med. 2004;34(1):1-8.
23. Tudor-Locke C, Hatano Y, Pangrazi RP, Kang M. Revisiting "how many steps are enough?". Med Sci Sports Exerc. 2008;40(7 Suppl):S537-S543.