In addition to occurring in normal cell division, telomere shortening is accelerated by oxidative stress. In vitro studies have suggested that a portion of the oxidative damage sustained by telomeres remains unrepaired and aff ects the amount of shortening in the next cell division.38,39 Furthermore, oxidative stress seems to downregulate telomerase activity in vascular smooth muscle cells40 and endothelial cells.41 An association between oxidative stress and telomere length has been reported in vivo too.42,43 Inflammation is another factor thought to contribute to telomere attrition in cells of the immune system by promoting leucocyte turnover.44,45 Oxidised LDL is inversely associated with telomerase activity in PBMCs46 and activates monocytes and macrophages by upregulating adhesion molecules and increasing production of infl ammatory cytokines.47 The increased production of certain cytokines has been shown to adversely aff ect telomerase activity.48 These oxidative stress and infl ammatory processes potentially pose threats to the telomere maintenance system. The most common causes of oxidative stress and inflammation stem from unhealthy nutrition, little exercise, obesity, metabolic syndrome, and chronic emotional stress. In the Harvard Nurses’ Health Study, higher intakes of red and processed meats, sweets, desserts, French fries, and refi ned grains increased blood markers of inflammation, whereas higher intakes of fruit, vegetables, legumes, fi sh, poultry, and whole grains decreased blood markers of infl ammation.49 Therefore, changes in diet, exercise, and stress management might decrease markers of oxidative stress and infl am mation.50,51 The diet used in this study might have benefi cial eff ects on many chronic diseases associated with older age. This diet is low in components (eg, saturated fats, cholesterol) that have been implicated in the development of diseases associated with ageing (including some types of cancer, cardiovascular diseases, diabetes, age-related macular degeneration, dementia) and high in several dietary constituents (eg, lycopene, antioxidants, carotenoids, zinc, fi bre, folate) that might decrease the risk of these conditions.51 Obesity, insulin resistance, and related cardiovascular disease processes, which are related to oxidative stress and infl ammation,52,53 have all been linked to shorter telomeres.54,55 Thus, improvements in these health conditions might favourably aff ect the regulation of telomerase activity. In a study that followed individuals over a 10-year period (but did not intervene in changing their weight), decreases in obesity were associated with increases in bulk telomere length, suggesting that shortening telomere length associated with obesity might be partially reversible.55 Also, in-vitro studies have shown that antioxidants reverse oxidative telomeric damage, prolonging the replicative lifespan and lowing telomere shortening.39 In summary, lifestyle factors known to promote cancer and cardiovascular disease processes might also adversely affect the telomere maintenance system, including telomerase.
Increased telomerase activity and comprehensive lifestyle changes: a pilot study Dean Ornish, Jue Lin*, Jennifer Daubenmier*, Gerdi Weidner, Elissa Epel, Colleen Kemp, Mark Jesus M Magbanua, Ruth Marlin, Loren Yglecias,Peter R Carroll, Elizabeth H Blackburn
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