scholarly journals The influence of physical exercise and sports on telomere length - A model for telomere length and telomerase activity regulation based on a comparative assessment of literature

Author(s):  
Paul F Lang ◽  
Kai-Uwe Fröhlich

Based upon a comprehensive analysis of current literature and by combining a molecular biology and a sports science perspective, this review examines (1) if a correlation between physical activity load and telomere length (TL) exists, and (2) comprehensively analyses and integrates molecular pathways regulating exercise dependent TL dynamics. The focus is on TL in leukocytes and muscle tissue in middle to advanced aged subjects. Regarding item (1), a strong tendency for an increase in mean leukocyte TL was found for exercise energy expenditures up to about 2∙103 kcal/week, while for higher activity levels no conclusive statement can be made. Conversely, research on skeletal muscle TL so far is quite limited but suggests that physical exercise with prolonged eccentric muscle contractions rather acts to shorten telomeres, while sports with little eccentric contractions might rather act to lengthen telomeres. As to item (2), a model for hypothetical pathways for exercise dependent telomerase activity regulation is proposed by consolidating findings of different studies in different cells. Consistent with this pathway model, various studies report increased telomerase transcription or activation by exercise. Moreover, a qualitative overall model for endurance exercise related TL dynamics is presented. It considers telomeres as dynamic structures in equilibrium between telomere shortening (e.g., cellular turnover, oxidative stress, inflammation) and telomere lengthening (e.g., telomerase activity, telomerase recruitment) effects. A negative feedback-loop mediated by enhanced telomerase recruitment to short telomeres is assumed to counteract too excessive TL alterations. Finally, a proposal is put forth for future research on exercise dependent telomere dynamics by adopting a systems biology approach to develop mathematical models that properly integrate the complexity of the interacting variables.

Author(s):  
Paul F Lang ◽  
Kai-Uwe Fröhlich

Based upon a comprehensive analysis of current literature and by combining a molecular biology and a sports science perspective, this review examines (1) if a correlation between physical activity load and telomere length (TL) exists, and (2) comprehensively analyses and integrates molecular pathways regulating exercise dependent TL dynamics. The focus is on TL in leukocytes and muscle tissue in middle to advanced aged subjects. Regarding item (1), a strong tendency for an increase in mean leukocyte TL was found for exercise energy expenditures up to about 2∙103 kcal/week, while for higher activity levels no conclusive statement can be made. Conversely, research on skeletal muscle TL so far is quite limited but suggests that physical exercise with prolonged eccentric muscle contractions rather acts to shorten telomeres, while sports with little eccentric contractions might rather act to lengthen telomeres. As to item (2), a model for hypothetical pathways for exercise dependent telomerase activity regulation is proposed by consolidating findings of different studies in different cells. Consistent with this pathway model, various studies report increased telomerase transcription or activation by exercise. Moreover, a qualitative overall model for endurance exercise related TL dynamics is presented. It considers telomeres as dynamic structures in equilibrium between telomere shortening (e.g., cellular turnover, oxidative stress, inflammation) and telomere lengthening (e.g., telomerase activity, telomerase recruitment) effects. A negative feedback-loop mediated by enhanced telomerase recruitment to short telomeres is assumed to counteract too excessive TL alterations. Finally, a proposal is put forth for future research on exercise dependent telomere dynamics by adopting a systems biology approach to develop mathematical models that properly integrate the complexity of the interacting variables.


Author(s):  
Jose C. Noguera ◽  
Alberto Velando

In wild animals, telomere attrition during early development has been linked with several fitness penalties throughout life. Telomerase enzyme can elongate telomeres, but it is generally assumed that its activity is suppressed in most somatic tissues upon birth. However, recent evidence suggests that this may not be the rule for long-lived bird species. We have therefore investigated whether telomerase activity is maintained during the postnatal growth period in a wild yellow-legged gull (Larus michahellis) population. Our results indicate that telomerase activity is not negligible in the blood cells, but activity levels sharply decline from hatching to fledging following a similar pattern to that observed in telomere length. Our results further suggest that the observed variation in telomere length may be the result of a negative effect of fast growth on telomerase activity, thus providing a new mechanism through which growth rates may affect telomere dynamics and potentially life-history trajectories.


2021 ◽  
Vol 14 (02) ◽  
pp. 891-901
Author(s):  
Lavanya Prathap ◽  
Prathap Suganthirababu S ◽  
Praveen Kumar K ◽  
Preetha S

Background: Physical exercise has its impact at the molecular level and aids in healthy well-being of an individual. The current systematic review emphasis on the impact of physical exercise on the telomere length in cancer prevention through epigenetic mechanism. Evidences support the impact of physical exercise in alteration of telomere length through its influence in telomerase activity. The aim of the systematic review is to analyze the effect of physical exercise in remodeling the telomere length in cancer prevention in an epigenetic prospect. Material and Methods: We conducted a qualitative systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covers articles ranging from the year 2010 to 2020. The Database used for literature searches are PubMed, Cochrane, Science Direct and Google scholar. The Medical Subject Headings (MeSH) used for search include ‘Cancer’ ‘exercise’ ‘Telomere length’ ‘telomerase expression’. The outcome variables include the telomere length, telomerase activity, telomere protein stabilizing gene expression status, Micro RNA expression status. Results: After exclusion of irrelevant articles 05 records are selected for final inclusion of the study and are analyzed using a Cochrane risk of bias assessment tool and SANRA tool found to be at low risk of bias and moderate quality respectively. The findings suggest chronic exercise is found to modulate the genetic and epigenetic equilibrium by either up regulation of p53 and p16 expression and stabilizing the telomerase activity within the limits or by increasing the telomerase activity and stabilizing the p53 and p16 expression within limits and impact telomere length, thus maintaining the genetic and epigenetic equilibrium. Conclusion: Based on the evidences collected it can be suggested that chronic moderate intensity aerobic exercise in a lifelong practice shows beneficial effects in a dose-response manner in cancer prevention in a novel way by modulating telomeres through epigenetic mechanism.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
J. Timothy Lightfoot

The literature strongly suggests that daily physical activity is genetically and biologically regulated. Potential identities of the responsible mechanisms are unclear, but little has been written concerning the possible evolutionary selection pressures leading to the development of genetic/biological controls of physical activity. Given the weak relationship between exercise endurance and activity levels and the differential genomic locations associated with the regulation of endurance and activity, it is probable that regulation of endurance and activity evolved separately. This hypothesis paper considers energy expenditures and duration of activity in hunter/gatherers, pretechnology farmers, and modern Western societies and considers the potential of each to selectively influence the development of activity regulation. Food availability is also considered given the known linkage of caloric restriction on physical activity as well as early data relating food oversupply to physical inactivity. Elucidating the selection pressures responsible for the genetic/biological control of activity will allow further consideration of these pressures on activity in today’s society, especially the linkages between food and activity. Further, current food abundance is removing the cues for activity that were present for the first 40,000 years of human evolution, and thus future research should investigate the effects of this abundance upon the mechanisms regulating activity.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Christian Werner ◽  
Milad Hanhoun ◽  
Janine Poess ◽  
Tobias Fuerster ◽  
Judith Haendeler ◽  
...  

Background: The vasoprotective effects of physical exercise are only partially understood on the molecular level. Telomere-associated proteins affect cellular senescence and survival. We studied the molecular effects of physical exercise in aortic tissue of running and sedentary mice. Methods: C57/Bl6 wildtype, endothelial nitric oxide synthase (ENOS) deficient and telomerase reverse transcriptase (TERT) deficient mice were randomized to voluntary running or no running wheel conditions (n=8 –10 per group). Results: Physical exercise for 3 weeks upregulated aortic telomerase activity to 303 ± 32% (p<0.01) of sedentary controls, increased protein expression telomere-repeat binding factor (TRF) 2 (254 ± 35%, p<0.05) and reduced protein expression of the senescence / apoptosis regulators Chk2 (41 ± 12%), p53 (51 ± 12%) and p16 (64 ± 19%). Running increased mRNA expression of TRF1 (193 ± 50%), TRF2 (192 ± 14%) and of the repair protein Ku70 (365 ± 121%). These exercise-induced changes were absent in ENOS −/− and TERT −/− mice. Aortic telomere length as determined by quantitative fluorescence in-situ hybridization (QFISH) did not differ between 3 week and 6 months old sedentary or running mice (1914 ± 166 vs. 1762 ± 394 telomere fluorescence units, TFU), but was lower in 18 months old sedentary control mice (1142 ± 117 TFU, p<0.05). To test the physiologic relevance of these exercise-mediated anti-senescent pathways, vascular oxidative stress was induced in-vivo by intraperitoneal injection of 25mg/kg paraquat for 24 hours before quantification of endothelial apoptosis in the thoracic aorta. Compared to sedentary mice, paraquat increased apoptotic cell death to 581 ± 48 %, whereas apoptosis was significantly lower in mice preconditioned by 21 days voluntary exercise (320 ± 34%, p<0.001 vs. control and paraquat). Conclusions: Voluntary physical activity upregulates aortic telomere regulating proteins which induces anti-senescent and anti-apoptotic effects mediated by ENOS and TERT independent of telomere length.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4236-4236 ◽  
Author(s):  
Seyed Hamidolah Ghaffari ◽  
Nilofar Shayan-Asl ◽  
Abdolhamid Jamialahmadi ◽  
Ardeshir Ghavamzadeh ◽  
Kamran Alimoghaddam

Abstract Introduction: The telomeric DNA together with its associated proteins protects the chromosome ends from degradation or aberrant recombination. Telomerase and telomere are extensively investigated as potential diagnostic and prognostic markers in human tumors. In this study, we aim to investigate the significance of telomerase activity (TA) and telomere length (TL) in patients with acute promyelocytic leukemia (APL). Methods: About 300 sequential peripheral blood mononuclear cell (PBMC) samples were collected from 40 patients with APL (32 newly diagnosed and 8 relapsed), at diagnosis, during and after therapy with Arsenic Trioxide. TA was assessed by TRAP-ELISA and -PAGE procedures. Terminal restriction fragment (TRF) length was determined by Southern blot analysis, using a Chemiluminescence-based assay. Quantification of PML-RARα/G6PDH transcripts was carried out by real-time PCR assay. Results: About 90% of the APL patients had a significant reduction in TRF length (median 3.5, ranged 2.3 to 6.7 kbp) relative to the age-matched control or to that at the time of CR (median 11.37; ranged 8.90 to 14.70 kbp) from the same patients (P<0.0001). A significance positive correlation between telomere length and PML-RARα expression was found in the APL patients (P=0.001). In all the APL patients, telomerase activity was elevated in comparison with normal individuals (P<0.001). The telomerase activity levels were significantly higher in patients with short TRF. The group of patients with shortened TRF and elevated TA had a significantly poorer overall survival. The levels of TA were even significantly higher and the TL size difference of leukemic from non-leukemic was significantly longer in relapsed patients than patients with the primary APL. Conclusion: Short telomere and high telomerase levels in the APL patients are mainly a consequence of extensive proliferative histories and they correlate with the disease progression. The shortened telomere length and the elevated telomerase activity may serve as prognostic factors for a subset of APL patients with more aggressive disease and poor outcome, and who may not respond favourably to arsenic therapy.


2010 ◽  
Vol 124 (7) ◽  
pp. 778-783 ◽  
Author(s):  
W Chen ◽  
S M Chen ◽  
Y Yu ◽  
B K Xiao ◽  
Z W Huang ◽  
...  

AbstractBackground and purpose:Telomere length must be maintained throughout cancer cell progression and proliferation. In most tumours, telomerase activity maintains telomere length. Therefore, telomerase is a target for cancer treatments. However, some cancer cells maintain telomere length through an alternative mechanism termed ‘alternative lengthening of telomeres’. To determine how telomerase inhibition relates to the initiation of the alternative lengthening of telomeres pathway, we investigated telomerase activity and telomere maintenance in Hep-2 cells with and without reduced telomerase activity.Materials and methods:We investigated telomerase activity levels in a normal Hep-2 cell line and in residual cells following telomerase inhibition treatment. Additionally, we looked for expression of a marker protein for the alternative lengthening of telomeres mechanism.Results and conclusions:In the residual cells, telomerase activity was eliminated. However, these cells had higher levels of the alternative lengthening of telomeres biomarker, suggesting an alternative mechanism for telomere maintenance following telomerase inhibition. These results could have a major impact on the design of new cancer treatments.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A150-A151
Author(s):  
Jamie Walker ◽  
Rebecca Campbell ◽  
Ivan Vargas

Abstract Introduction Insomnia and depression are highly comorbid and have been shown to be independently associated with lower levels of physical activity. It is not clear, however, if being less physically active is a risk factor for or consequence of depression and insomnia. The factors that explain the associations between insomnia, depression, and physical activity are likely complex and overlapping. For example, insomnia may predict inactivity by impacting one’s energy levels, leaving them too tired to exercise. Insomnia may also interfere with one’s motivation to exercise due to low mood, as insomnia is associated with the development of depressive symptoms. The purpose of the present study was to explore whether depression mediated the link between insomnia and low levels of physical activity. Methods A national online survey was conducted from April-June 2020. Participants completed surveys to assess demographics, mood, sleep, and physical activity. Depressive symptoms were estimated with the Center for Epidemiologic Studies Depression Scale (CES-D). Insomnia symptoms were estimated with the Insomnia Severity Index (ISI). Physical activity levels were estimated with the International Physical Activity Questionnaire (IPAQ). Analyses were conducted using multiple linear regression, with separate models for depression, insomnia, and the combination of the two, on levels of physical activity. Results 3,952 adults (Mage = 46.9 years) completed the survey. According to the unadjusted models, greater insomnia symptoms were associated with greater depressive symptoms (b = 0.4523, SE = 0.019593, p &lt; .001), and lower levels of physical activity (b = -38.741, SE = 18.236, p = 0.0337). The relationship between insomnia and physical activity was no longer significant, however, when controlling for depression (b = -6.140, SE = 19.274, p = 0.75). According to the mediation analyses, there was an indirect effect of insomnia on physical activity that was explained by differences in depressive symptoms (Sobel Test = -4.895, SE = 6.518, p &lt; .001). Conclusion Our findings support previous research indicating associations between symptoms of insomnia and depression and physical activity. Future research should examine if these same results hold using a longitudinal design. Support (if any) Vargas: K23HL141581


2020 ◽  
Author(s):  
Gema Insa-Sánchez ◽  
Lorena Fuentes-Broto ◽  
Alberto Cobos ◽  
Elvira Orduna Hospital ◽  
Francisco Segura ◽  
...  

<b><i>Introduction:</i></b> Our aim was to evaluate the changes in choroidal thickness (CT) and volume (CV) following aerobic physical exercise in healthy young adults. <b><i>Methods:</i></b> This study included 72 eyes from healthy volunteers between 22 and 37 years old. Using the International Physical Activity Questionnaire, total physical activity was computed. Measurements using an autorefractometer, ocular biometry, and spectral-domain optical coherence tomography using the Enhanced Depth Imaging protocol were taken. OCT was performed as a baseline measurement and after performing 10 min of dynamic physical exercise (3 and 10 min post-exercise). The choroidal layer was manually segmented, and the CT and CV in different areas from the Early Treatment Diabetic Retinopathy Study grid were obtained. <b><i>Results:</i></b> In healthy adults, at 3 min post-exercise, CT was higher in the subfoveal, the 3-mm nasal, and the 6-mm superior areas. Between 3 and 10 min post-exercise, the CT was reduced in all areas, and in some areas, the values were even smaller than the baseline measurements. The CV values showed changes after exercise similar to those of thickness. The total CV recovery after exercise was related to sex and physical activity level. <b><i>Conclusion:</i></b> Individuals with higher physical activity habits had greater CV at rest than those with lower physical activity levels. During exercise, healthy young people adjust CT and CV. At 3 min post-exercise, CT and CV increase. Women and individuals with greater physical activity levels reduce their total CV more than others during recovery.


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