I have frequently asserted that telomere lengths do not decline in a uniform manner through life but depend on the interaction of multiple endogenous and extrinsic factors. Two important factors are stress and exercise. A new study in Plos One lends light on the relationship among these factors and telomere lengths: The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length. This blog entry reviews interesting previous research relating to the impacts of stress and exercise on telomere lengths and describes the new findings. For background, there is the Telomere Shortening and Damage theory of aging described in my treatise and a number of previous posts relating to telomere lengths which you can find by searching in this blog.
There are many forms of stress, social, physical and emotional, and these may be temporary, recurring or chronic. Stress can result from external sources like injury or loss of a relative or result from internal conditions like a disease or mood disorder. In the blog entries Stress and longevity and Hormesis and age retardation I discussed how some manageable forms of body stress can lead to a hormetic response, mobilization of heat shock proteins that actually confer health and longevity benefits, while more intense or more prolonged forms of stress may lead to multiple pathological conditions and premature aging. For example, the stress of parachute jumping could possibly be good for you as suggested in the publication Emotional stress induced by parachute jumping enhances blood nerve growth factor levels and the distribution of nerve growth factor receptors in lymphocytes. On the other hand, stress of prolonged unemployment could be bad for you even after you find a job, as suggested in the report History of unemployment predicts future elevations in C-reactive protein among male participants. I also discussed how several dietary supplements like curcumin exercise positive effects in part through activating the body’s heat-shock stress response.
There is a significant body of research literature associated with the negative effects of chronic or excess stress including immune system dysregulation, premature immunosenescence, elevated blood pressure and cortisol response, and undetected Type 2 diabetes(ref)(ref)(ref)(ref)(ref)(ref)(ref)(ref) which I will not review here. Such stress is often viewed as associated with accelerated aging.
Telomeres, telomerase and stress
The 2004 publication Accelerated telomere shortening in response to life stress was one of the first of many to link telomere shortening to stress. “We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress–both perceived stress and chronicity of stress–is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women.”
A 2006 study suggested that telomere shortening could be a mechanism through which stress leads to accelerated aging: Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. “Little is known about the biological mechanisms underlying the excess medical morbidity and mortality associated with mood disorders. Substantial evidence supports abnormalities in stress-related biological systems in depression. Accelerated telomere shortening may reflect stress-related oxidative damage to cells and accelerated aging, and severe psychosocial stress has been linked to telomere shortening. We propose that chronic stress associated with mood disorders may contribute to excess vulnerability for diseases of aging such as cardiovascular disease and possibly some cancers through accelerated organismal aging. METHODS: Telomere length was measured by Southern Analysis in 44 individuals with chronic mood disorders and 44 nonpsychiatrically ill age-matched control subjects. RESULTS: Telomere length was significantly shorter in those with mood disorders, representing as much as 10 years of accelerated aging. — These results provide preliminary evidence that mood disorders are associated with accelerated aging and may suggest a novel mechanism for mood disorder-associated morbidity and mortality.”
The 2006 report Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study suggests another key link between telomere lengths, insulin resistance and hypertension. ”Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance.”
A May 2010 publication Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls advances the hypothesis that stress leads to accelerated aging via telomere shortening. “Accelerated leukocyte telomere shortening has been previously associated to self-perceived stress and psychiatric disorders, including schizophrenia and mood disorders. We set out to investigate whether telomere length is affected in patients with anxiety disorders in which stress is a known risk factor. We also studied the effects of childhood and recent psychological distress on telomere length. We utilized samples from the nationally representative population-based Health 2000 Survey that was carried out between 2000-2001 in Finland to assess major public health problems and their determinants. — Our results suggest that childhood stress might lead to accelerated telomere shortening seen at the adult age.”
Another slightly earlier 2010 study Childhood maltreatment and telomere shortening: preliminary support for an effect of early stress on cellular aging had the same theme, that childhood stress can lead to shorter telomeres and perhaps accelerated aging in adult life. “Based on previous evidence linking psychosocial stress to shorter telomere length, this study was designed to evaluate the effect of childhood adversity on telomere length. — These results extend previous reports linking shortened leukocyte telomere length and caregiver stress to more remote stressful experiences in childhood and suggest that childhood maltreatment could influence cellular aging.”
Telomere lengths stress and exercise
The first articles to show up relating telomerase and telomere lengths to exercise seemed to express surprise that exercise did not affect observed levels of telomerase, like the 2001 paper Telomerase activity is not altered by regular strenuous exercise in skeletal muscle or by sarcoma in liver of rats. “We conclude that mild and strenuous exercise training does not significantly affect the activity of telomerase in the systems studied. Exercise training during sarcoma significantly retards the development of tumors and could possibly serve as a positive adjunct to treatment.”
A 2003 study looked at the result of exercise fatigue: Athletes with exercise-associated fatigue have abnormally short muscle DNA telomeres. “In this study, we have compared a marker of skeletal muscle regeneration of athletes with exercise-associated chronic fatigue, a condition labeled the “fatigued athlete myopathic syndrome” (FAMS), with healthy asymptomatic age- and mileage-matched control endurance athletes. — The minimum value of TRF lengths (4.0 +/- 1.8 kb) measured on the DNA from vastus lateralis biopsies from these athletes were significantly shorter than those from 13 age- and mileage-matched control athletes (5.4 +/- 0.6 kb, P < 0.05). Three of the FAMS patients had extremely short telomeres (1.0 +/- 0.3 kb). The minimum TRF lengths of the remaining 10 symptomatic athletes (4.9 +/- 0.5 kb, P < 0.05) were also significantly shorter that those of the control athletes.”
The 2008 paper The effects of regular strength training on telomere length in human skeletal muscle reported “A recent study has reported abnormally short telomeres in skeletal muscle of athletes with exercise-associated fatigue. This important report raises the question of whether long-term practice of sports might have deleterious effects on muscle telomeres. Therefore, we aimed to compare telomere length of a group of power lifters (PL; N = 7) who trained for 8 +/- 3 yr against that of a group of healthy, active subjects (C; N = 7) with no history of strength training. — CONCLUSION: These results show for the first time that long-term training is not associated with an abnormal shortening of skeletal muscle telomere length. Although the minimum telomere length in PL remains within normal physiological ranges, a heavier load put on the muscles means a shorter minimum TRF length in skeletal muscle.”
A recent 2010 paper looks at the long-term consequences of strenuous exercise on telomere lengths: Skeletal muscle telomere length in healthy, experienced, endurance runners. “Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 +/- 7 years) to those of 19 sedentary individuals (mean age: 39 +/- 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running (r = -0.63, P = 0.007) and hours spent training (r = -0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRF length, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.”
Telomere length, stress and exercise
Finally, a new twist is suggested in the publication: The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length. “Chronic psychological stress is associated with detrimental effects on physical health, and may operate in part through accelerated cell aging, as indexed by shorter telomeres at the ends of chromosomes. However, not all people under stress have distinctly short telomeres, and we examined whether exercise can serve a stress-buffering function. We predicted that chronic stress would be related to short telomere length (TL) in sedentary individuals, whereas in those who exercise, stress would not have measurable effects on telomere shortening. — Participants were categorized into two groups-sedentary and active (those getting Centers for Disease Control-recommended daily amount of activity). The likelihood of having short versus long telomeres was calculated as a function of stress and exercise group, covarying age, BMI and education. Logistic regression analyses revealed a significant moderating effect of exercise. 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.
I remind my readers of the January 2010 blog post Vitamins, supplements and telomerase – upregulation or downregulation? That post points to a study in which telomere lengthening was observed over a long period of time for a sizeable portion of the population studied. As stated in my treatise, “It appears that taking a number of popular supplements in the anti-aging firewalls supplement regimen like Vitamin E, fish oils, Vitamin D3 and resveratrol can lead to telomeres being longer than they otherwise might be, possibly because they induce the production of telomerase, possibly for other reasons. And, several of these supplements actually turn off telomerase in cancer cells.”
To sum it up
o Childhood stress resulting in shorter telomeres may result in accelerated cellular aging later in life.
o There is a “sweet spot” range for exercise stress within which the impact of the exercise is positive and health-producing and there is no stress-related telomere erosion, even if the exercise is repeated over the long term. The sweet spot range may depend on the state of the individual.
o If exercise is pursued too vigorously, to the point where it produces chronic fatigue, or pursued consistently as an endurance activity, telomere erosion may ensue, at least in muscles.
o Psychological stress can produce telomere erosion even within a few days, but “sweet spot” exercising can prevent such erosion.
– There is much complication involved with telomere shortening or lengthening involving diet, health and age as well as stress and exercise. The interplay of these and multiple internal factors is not well understood. Most likely there are epigenetic regulators of telomere length and every day, perhaps every hour or minute, complicated programs throughout the body readjust telomere lengths, perhaps making them shorter, leaving them the same or even making them longer.
– How telomerase activators like cycloastragenol play into the situation of lengthening telomeres is also not well understood. See my April 2010 post Telomerase activators – what do they really do?