This blog entry provides an update on 2010 research relating to how certain everyday factors such as lifestyle, exercise and diet affect telomere lengths.
This is the second in a 3-part mini-series of blog posts concerned with the implications of telomere lengths. Part1 was concerned with telomere lengths, cancers and disease processes. There I focused on a couple of specific questions: Are shorter telomere lengths predictive of cancers and other disease processes? And, are disease processes or unhealthful body conditions characterized by shorter telomere lengths? I have also produced a Part 3 post concerned with the molecular biology of telomere length management focused on such subjects as the role of HSP-90 and P23 in regulation of telomere lengthening by telomerase. That post will also state some of my views of the implications of telomere-related knowledge for healthy aging.
If you are new to the subject of telomeres and telomerase, I suggest you start with the telomere/telomerase discussion in my treatise. The discussion there provides background on telomeres, telomere shortening and lengthening, and the importance of telomere biology for aging. I have also published a number of blog posts that provide much additional background including:
The purpose of this current blog post is to cover some selected 2010 research not already discussed in my treatise or in the above blog entries. I also weigh in with opinions on a few key points.
Telomere lengths and processed meats
It is possible to couple the results of two studies related to processed meats to see some interesting relationships. The first such study is described in a 2010 publication published in Circulation, a journal of the American Heart Association Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus. This study is a meta-analysis of studies relating red and processed meat to CHD (coronary heart disease), stroke, and diabetes mellitus. “Background— Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary. — Methods and Results— We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23; P for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46; P=0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89; P=0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27; P<0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships. — Conclusions— Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.”
The second study (2008) looks at telomere lengths as related to kinds of food intake Dietary patterns, food groups, and telomere length in the Multi-Ethnic Study of Atherosclerosis (MESA). “Objective: With data from 840 white, black, and Hispanic adults from the Multi-Ethnic Study of Atherosclerosis, we studied cross-sectional associations between telomere length and dietary patterns and foods and beverages that were associated with markers of inflammation. — Design: Leukocyte telomere length was measured by quantitative polymerase chain reaction. Length was calculated as the amount of telomeric DNA (T) divided by the amount of a single-copy control DNA (S) (T/S ratio). Intake of whole grains, fruit and vegetables, low-fat dairy, nuts or seeds, nonfried fish, coffee, refined grains, fried foods, red meat, processed meat, and sugar-sweetened soda were computed with responses to a 120-item food-frequency questionnaire completed at baseline. Scores on 2 previously defined empirical dietary patterns were also computed for each participant. Results: After adjustment for age, other demographics, lifestyle factors, and intakes of other foods or beverages, only processed meat intake was associated with telomere length. For every 1 serving/d greater intake of processed meat, the T/S ratio was 0.07 smaller (Î² ± SE: –0.07 ± 0.03, P = 0.006). Categorical analysis showed that participants consuming 1 serving of processed meat each week had 0.017 smaller T/S ratios than did nonconsumers. Other foods or beverages and the 2 dietary patterns were not associated with telomere length. — Conclusions: Processed meat intake showed an expected inverse association with telomere length, but other diet features did not show their expected associations.
So, together the two studies say:
· Consumption of processed meat correlates with both shorter telomere lengths and increased susceptibility to CHD and diabetes mellitus. Neither of these correlations exist for consumption of red meat.
· Of a number of possibly not-good-for-you foods like sugar-sweetened soda, only consumption of processed meats was correlated with shorter telomeres.
· Causal chain is unclear, e.g. whether eating processed meats leads to shorter telomeres which leads to increased disease susceptibilities or whether eating processed meats leads to disease susceptibilities which lead to shorter telomeres, or both or neither.
From a health and longevity perspective the two studies combine fairly powerfully to contraindicate eating processed meats, foods which have long been suspected to be carcinogenic because they tend to be infused with nitrites(ref).
Telomere lengths, dietary and lifestyle factors in middle-aged and older women
The 2010 publication Associations between diet, lifestyle factors, and telomere length in women reports “Background: Leukocyte telomere length is associated with diseases of aging, but there is limited knowledge of diet and lifestyle determinants. — Objective: The objective was to examine cross-sectionally the association between diet, body composition, and lifestyle factors on leukocyte telomere length in women. — Design: Leukocyte telomere length was measured by quantitative polymerase chain reaction in 2284 female participants from the Nurses’ Health Study, who were selected as controls for an investigation of biological predictors of cancer. Diet, lifestyle, and anthropometric data were assessed by questionnaire. — Results: After multivariate adjustment, dietary fiber intake was positively associated with telomere length (z score), specifically cereal fiber, with an increase of 0.19 units between the lowest and highest quintiles (P = 0.007, P for trend = 0.03). Although total fat intake was not associated with telomere length, polyunsaturated fatty acid intake (–0.26 units, quintile 5 compared with quintile 1: P = 0.002, P for trend = 0.02), specifically linoleic acid intake, was inversely associated with telomere length after multivariate adjustment (–0.32 units; P = 0.001, P for trend = 0.05). Waist circumference was inversely associated with telomere length [0.15-unit difference in z score in a comparison of the highest (
I find the dietary associations with telomere lengths in this study of women to be not at all surprising. However, the assertions in the statement “We found no association between telomere length and smoking, physical activity, or postmenopausal hormone use” are surprising though they indeed may represent the data at hand. Other well-designed studies have come up with contradictory conclusions:
· With respect to smoking, the 2005 publication Obesity, cigarette smoking, and telomere length in women found, for a sample of 1122 white women aged 18-76 years “A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort.” This study, incidentally, also correlated obesity with shorter telomeres. “Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026).” — . Our results emphasize the pro-ageing effects of obesity and cigarette smoking.” Other studies also support a strong correlation between cigarette smoking and telomere erosion. The 2008 study Telomere Length, Cigarette Smoking, and Bladder Cancer Risk in Men and Women reports “We also observed a significant difference in telomere length across categories of pack-years of smoking (P = 0.01).”
· With regard to exercise, in the blog entry Stress, exercise and telomere lengths I discuss a small research study that indicates that women who are under psychological stress and who participate in moderate exercise find the telomere-shortening effect of the stress nullified. “As predicted, among non-exercisers a one unit increase in the Perceived Stress Scale was related to a 15-fold increase in the odds of having short telomeres (p<.05), whereas in exercisers, perceived stress appears to be unrelated to TL (B = âˆ’.59, SE = .78, p = .45).” This was a relatively small (63 healthy post-menopausal women aged between 54 and 82) and short (3 days) study using a self-evaluation 10-item questionnaire to measure psychological stress. Nonetheless the implication is most interesting: exercise can nullify erosion in telomere lengths due to psychological stress.”
· With respect to postmenopausal hormone use, again we seem to have a contradiction, this time as exemplified by the 2005 publication Effect of Long-Term Hormone Therapy on Telomere Length in Postmenopausal Women. “Relative telomere length ratios in the HT group (65 women who had been on estrogen and progesterone therapy for more than five years) were significantly greater than those in the non-HT group (p<0.01). HT was significantly correlated with the relative telomere length ratio in multivariate analysis when potential confounding variables were controlled for (p<0.05). In conclusion, telomere lengths were longer in postmenopausal women who had a history of long-term HT than in postmenopausal women without HT. Long-term HT in postmenopausal women may alleviate telomere attrition.”
Telomere lengths in coronary heart disease patients as associated with Omega-3 fatty acid levels.
The 2010 JAMA publication Association of Marine Omega-3 Fatty Acid Levels With Telomeric Aging in Patients With Coronary Heart Disease reports on a special population but comes to what I believe is a generally-valid conclusion. “Context: Increased dietary intake of marine omega-3 fatty acids is associated with prolonged survival in patients with coronary heart disease. However, the mechanisms underlying this protective effect are poorly understood. – Objective: To investigate the association of omega-3 fatty acid blood levels with temporal changes in telomere length, an emerging marker of biological age. — Design, Setting, and Participants: Prospective cohort study of 608 ambulatory outpatients in California with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years). — Main Outcome Measures: We measured leukocyte telomere length at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length. Results: Individuals in the lowest quartile of DHA+EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; P < .001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted Î² coefficient x 10–3 = 0.06; 95% CI, 0.02-0.10) and after (adjusted Î² coefficient x 10–3 = 0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-SD increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98). – Conclusion: Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.” I suspect this conclusion generalizes beyond CHD patients.
Telomere lengths and marital status
I am getting fairly good at predicting the outcomes of telomere length studies just from the titles of the studies. An example is the October 2010 study Leukocyte telomere length and marital status among middle-aged adults. My reasoning is “of course telomere lengths will generally be longer in married people, because they on the whole are probably less stressed.” The study reports: “Background: being unmarried is associated with worse health and increased mortality risk. Telomere length has emerged as a marker for biological ageing but it is unclear how telomere length relates to marital status. Objective: to examine the relationship between telomere length and marital status in a sample of middle-aged adults. Design and subjects: cross-sectional analysis among 321 adults aged 40-64 years. — Methods: telomere length was measured by PCR (T/S ratio). Participants provided information on healthy lifestyle activities including smoking, alcohol use, diet, exercise, obesity as well as social support. — Results: participants married or living with a partner had a mean T/S ratio of 1.70 and those widowed, divorced, separated or never married had a mean T/S ratio of 1.58 in a model adjusted for age, gender and race/ethnicity (P < 0.001). When the analysis was further adjusted for diet, alcohol consumption, exercise, smoking, social support, poverty and obesity, persons married or living with a partner had a higher mean T/S ratio of 1.69 than their unmarried counterparts (1.59) (P = 0.004). — Conclusions: these results indicate that unmarried individuals have shorter telomeres. This relationship between marital status and telomere length is independent of presumed benefits of marriage such as social support and a healthier lifestyle.” OK. No surprise here.
Telomere length, lifestyle and risk of coronary atherosclerosis
The September 2010 publication Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium offers a somewhat more subtle message. “The telomere length is an indicator of biologic aging, and shorter telomeres have been associated with coronary artery calcium (CAC), a validated indicator of coronary atherosclerosis. It is unclear, however, whether healthy lifestyle behaviors affect the relation between telomere length and CAC. In a sample of subjects aged 40 to 64 years with no previous diagnosis of coronary heart disease, stroke, diabetes mellitus, or cancer (n = 318), healthy lifestyle behaviors of greater fruit and vegetable consumption, lower meat consumption, exercise, being at a healthy weight, and the presence of social support were examined to determine whether they attenuated the association between a shorter telomere length and the presence of CAC. Logistic regression analyses controlling for age, gender, race/ethnicity, and Framingham risk score revealed that the relation between having shorter telomeres and the presence of CAC was attenuated in the presence of high social support, low meat consumption, and high fruit and vegetable consumption. Those with shorter telomeres and these characteristics were not significantly different from those with longer telomeres. Conversely, the subjects with shorter telomeres and less healthy lifestyles had a significantly increased risk of the presence of CAC: low fruit and vegetable consumption (odds ratio 3.30, 95% confidence interval 1.61 to 6.75), high meat consumption (odds ratio 3.33, 95% confidence interval 1.54 to 7.20), and low social support (odds ratio 2.58, 95% confidence interval 1.24 to 5.37). Stratification by gender yielded similar results for men; however, among women, only fruit and vegetable consumption attenuated the shorter telomere length and CAC relation. In conclusion, the results of the present study suggest that being involved in healthy lifestyle behaviors might attenuate the association between shorter telomere length and coronary atherosclerosis, as identified using CAC.” The message here is worth emphasis: What seems to be very important for reducing the risk of coronary atherosclerosis (by lowering coronary artery calcium) is the healthy lifestyle behavior, and whether telomeres are longer or shorter is secondary.
In summary, drawing not only on the above but on previously-reported studies:
· Population study results sometimes appear to come to contradictory conclusions with respect to what shortens telomere lengths.
· In general, it appears that negative health conditions like smoking, obesity or poor diet results in shorter telomeres.
· Conditions that tend to reduce stress like being partnered tend to keep telomeres longer.
· Interventions that enhance health like hormone replacement therapy, consuming Omega-3 oils or good diet tend to keep telomeres longer.
· There can be considerable variability in telomere lengths both across studies and within individual studies.
There is much more to be said about telomere shortening/lengthening and even more to be learned. The Part 3 post for this miniseries on telomere shortening is concerned with some of the key biomolecular mechanisms involved with telomere lengthening via telomerase. Also, in that post I will recapitulate my current views on the implications of telomere science for longevity.