Improvements in Nutrition and Lifestyle Increase Telomerase Activity

Introduction

Telomeres, the protective DNA–protein complexes at the end of chromosomes, are required for DNA replication and to protect chromosomes from nuclease degradation, end-to-end fusion, and the initiation of cellular senescence. Since telomeres shorten with each cell division, telomere length is a key indicator of mitotic cell aging and viability.

Telomere length has emerged as a prognostic indicator of disease risk, progression, and premature mortality in humans. Shortened telomeres are a precursor to the initiation of many types of cancer and are predictive of increased risk of bladder, head and neck, lung and renal-cell cancers; poor clinical outcomes in breast and colorectal cancer; recurrence of prostate cancer in patients undergoing radical prostatectomy; and decreased survival in patients with coronary heart disease and infectious disease^{1 2 3 4 5 6 7 8}.

However, even cells with shortened telomeres can remain genetically stable if the enzyme telomerase, which adds telomeric repeat sequences to the chromosomal DNA ends preserving telomere length and healthy cell function, is fully operational.^{1 9 10}

The converse is also true. Decreased telomerase activity alone has been linked to increased risk of cardiovascular disease, independent of chronological age. In a study involving healthy women, telomerase activity, but not telomere length, in immune cells (specifically, peripheral blood mononuclear cells or PBMCs) was inversely associated with six major cardiovascular disease risk factors.¹¹ Telomerase activity is also adversely affected by obesity and insulin resistance, another way in which both result in decreasing telomere length.¹² Thus telomerase activity may offer an earlier prognosticator of genomic stability and long-term cellular viability than telomere length.

Can telomerase activity be increased by improvements in diet and lifestyle?

Published in the November 2008 issue of Lancet Oncology, Dr. Dean Ornish’s latest research, a pilot study on the effects of dietary and lifestyle changes in 30 men with low risk prostate cancer, suggests the answer is a resounding “Yes!” PBMC telomerase activity in these men increased 29.84% within just 3 months of making significant, yet simple, changes in diet and lifestyle.¹

Telomerase-Enhancing Diet, Supplement and Lifestyle Program

After a 3-day intensive residential retreat, the men were placed on a low-fat (10% of calories from fat), whole foods, plant-based diet, centered on vegetables, fruits, unrefined grains, and legumes. Intake of refined carbohydrates was minimized. The diet was supplemented with soy (one daily serving of tofu plus 58 grams of a fortified soy protein powdered beverage), fish oil (3 grams daily), vitamin E (100 IU daily), selenium (200 μg daily), and vitamin C (2 grams daily).

In addition, subjects participated in moderate aerobic exercise (walking 30 min/day, 6 days/week); stress management (gentle yoga-based stretching, breathing, meditation, imagery, and progressive relaxation techniques 60 min/day, 6 days/week), and a 1-hour group support session once per week. Participants also met with staff 4 hours per week and had one weekly telephone contact with a study nurse.

Compliance was excellent for both lifestyle and dietary recommendations. After 3 months, subjects reported consuming an average11.6% of calories from fat per day, exercising an average of 3.6 hours each week, and practicing stress management techniques an average of 4.5 hours each week. All medications remained unchanged throughout the 3-month trial, with the exception of participant whose statin drug dosage was decreased.

Additional Benefits

The increased telomerase activity in this study was accompanied by decreases in perceived psychological distress and LDL cholesterol. While the exact mechanism(s) behind these beneficial outcomes is unknown, study authors hypothesize the following as potential contributing factors:

Decreased psychological stress

Overexposure to stress-related hormones (catecholamines and cortisol) increases oxidative damage to cells, compromising the telomere maintenance system.^{13 14 15}

Chronic psychological distress has been associated with shorter telomeres and lower telomerase activity in PBMCs. Significantly greater chronic stress, negative mood, greater oxidative stress and nocturnal excretion of urinary epinephrine was noted in healthy women whose PBMC telomerase activity was below the mean compared to those with higher telomerase activity.^{1 16 17 18 19 20}

Decreased inflammation

Oxidative stress and inflammation are key common factors in cardiovascular disease processes, obesity, insulin resistance, and type 2 diabetes—all of which are associated with shorter telomeres.

Oxidized LDL activates monocytes and macrophages by upregulating adhesion molecules and increasing production of inflammatory cytokines. The increased production of certain cytokines has been shown to adversely affect telomerase activity.^{21 22 23}

Inflammation-related increases in oxidative stress not only accelerate telomere shortening, but have been shown to downregulate telomerase activity in vitro (in vascular smooth muscle cells endothelial cells) and in vivo (in patients with type 2 diabetes).^{24 25 26}

Decreased diet-related oxidative stress

The Western dietary pattern [a.k.a. the Standard American Diet], (characterized by higher intakes of red and processed meats, sweets, desserts, French fries, refined grains and a 20:1 omega6:omega3 ratio), has been shown to be highly pro-inflammatory. In contrast, a prudent dietary pattern, (characterized by higher intakes of vegetables, fruit, legumes, fish, poultry and whole grains and an omega-6:omega-3 ratio ~4:1), is inversely associated with key markers of inflammation.²⁷

Furthermore, the Western dietary pattern promotes development of obesity, the metabolic syndrome, and type 2 diabetes, all of which increase inflammation and oxidative stress.^{28 29 30}

Obesity is associated with low-grade inflammation in white adipose tissue resulting from chronic activation of the innate immune system, which can lead to insulin resistance, impaired glucose tolerance and diabetes.^{31 32}

Obesity is also associated with increased inflammation because white adipose tissue is a major source of inflammatory cytokines. Inflammation promotes an increase in white blood cell turnover, which further increases telomere attrition. Not surprisingly, obese adults have shorter telomeres than their normal-weight counterparts.³³

A study that followed 70 individuals over a 10-12 year period to investigate the correlation between insulin resistance and telomere attrition found, not only that telomere attrition increased along with insulin resistance, but that in several individuals who lost weight, telomere length increased, suggesting that obesity-associated telomere loss may be reversible.³⁴

Regular, moderate exercise

Although infrequent bouts of both aerobic and anaerobic exercise can induce oxidative stress, regular exercise upregulates endogenous antioxidant defenses.^{35 36}

Interestingly, it appears that exercise involving moderate, but not low or high energy expenditure, provides a protective effect on PBMC telomere length. Researchers looked at the relationship of exercise energy expenditure (EEE) with both telomere length and telomerase activity. Sixty-nine participants (34 men, 35 women aged 50-70 years) were assessed for weekly EEE level using the Yale Physical Activity Survey. Lifetime consistency of EEE was also determined. Subjects spanned a large range of weekly EEE levels, which were separated into quartiles: 0-990, 991-2340, 2341-3540, and >3541 kcal/week. Subjects in the second and third EEE quartiles exhibited significantly longer telomere lengths than those in both the first and fourth EEE quartiles. Telomerase activity did not differ among the EEE quartiles, but an association was seen between telomerase enzyme activity and hTERT genotype—the TT genotype had significantly greater telomerase enzyme activity than the CT and CC groups. So, while individuals with the TT genotype may be gifted with a more active telomerase enzyme, consistent moderate exercise appears to be a more important factor in maintaining telomere length.³⁷

Combining moderate exercise with a healthy diet may offer the most benefit in the shortest amount of time. Placing men on a regimen combining a low-fat, high-fiber diet with 45-60 minutes of daily exercise resulted in dramatic improvements in oxidative stress, nitric oxide availability, blood pressure and the metabolic profile [serum lipid, insulin, 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), and glucose measurements]within just 3 weeks.³⁸

Conclusion

In sum, diet and lifestyle factors known to promote inflammation and oxidative stress adversely affect telomerase. Fortunately, the reverse is also true. Telomerase activity can be restored via a diet centered around whole plant foods, key supplements, regular moderate exercise and stress management.

References