scholarly journals The effect of long-term ultra-endurance exercise and SOD2 genotype on telomere shortening with age

2020 ◽  
Vol 129 (4) ◽  
pp. 873-879 ◽  
Author(s):  
Barbara Hernando ◽  
Marta Gil-Barrachina ◽  
Elena Tomás-Bort ◽  
Ignacio Martinez-Navarro ◽  
Eladio Collado-Boira ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Endurance Training ◽  
Telomere Length ◽  
Endurance Exercise ◽  
Biological Aging ◽  
Acute Inflammatory Response ◽  
Telomere Shortening ◽  
Ultra Endurance ◽  
First Time

Habitual ultra-endurance exercise seems to promote telomere length maintenance, especially at older ages. In addition, the beneficial effect of ultra-endurance training on biological aging is higher in ultra-trail runners who have been engaged to ultra-endurance training during many years. Finally, and for the first time, this study shows that the SOD2 rs4880 polymorphism has a significant impact on telomere length, as well as on acute inflammatory response to a 107-km trail race.

scholarly journals Nestling telomere shortening, but not telomere length, reflects developmental stress and predicts survival in wild birds

2014 ◽  
Vol 281 (1785) ◽  
pp. 20133287 ◽  
Author(s):  
Jelle J. Boonekamp ◽  
G. A. Mulder ◽  
H. Martijn Salomons ◽  
Cor Dijkstra ◽  
Simon Verhulst
Keyword(s):  
Telomere Length ◽  
Brood Size ◽  
Developmental Stress ◽  
Free Living ◽  
Telomere Shortening ◽  
Developmental Effects ◽  
Fitness Consequences ◽  
Developmental Conditions ◽  
Fledgling Mass

Developmental stressors often have long-term fitness consequences, but linking offspring traits to fitness prospects has remained a challenge. Telomere length predicts mortality in adult birds, and may provide a link between developmental conditions and fitness prospects. Here, we examine the effects of manipulated brood size on growth, telomere dynamics and post-fledging survival in free-living jackdaws. Nestlings in enlarged broods achieved lower mass and lost 21% more telomere repeats relative to nestlings in reduced broods, showing that developmental stress accelerates telomere shortening. Adult telomere length was positively correlated with their telomere length as nestling ( r = 0.83). Thus, an advantage of long telomeres in nestlings is carried through to adulthood. Nestling telomere shortening predicted post-fledging survival and recruitment independent of manipulation and fledgling mass. This effect was strong, with a threefold difference in recruitment probability over the telomere shortening range. By contrast, absolute telomere length was neither affected by brood size manipulation nor related to survival. We conclude that telomere loss, but not absolute telomere length, links developmental conditions to subsequent survival and suggest that telomere shortening may provide a key to unravelling the physiological causes of developmental effects on fitness.

scholarly journals Leukocyte telomere length in patients with multiple sclerosis and its association with clinical phenotypes

2020 ◽  
Author(s):  
Michael Hecker ◽  
Brit Fitzner ◽  
Kathrin Jäger ◽  
Jan Bühring ◽  
Margit Schwartz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Telomere Shortening ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
Age And Sex

AbstractAging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS.We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS) and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex.The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis.Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.Research in contextEvidence before this studyThere is a growing research interest in the relationship between age and the pathophysiology and clinical presentation of multiple sclerosis (MS). Telomere shortening is a hallmark of biological aging. However, the role of telomeres in this chronic immune-mediated neurodegenerative disease has not yet been widely studied. Two research groups provided evidence that the telomeres of immune cells in the peripheral blood are shorter in patients with MS than in healthy subjects.Added value of this studyWe found that leukocytes from patients with relapsing-remitting MS (RRMS) are characterized by relatively short telomere lengths (TL). On average, we observed 18% shorter TL in the RRMS patient cohort (n=40) than in the age- and sex-matched healthy control cohort (n=60). We further analyzed the association of TL and long-term clinical outcomes. RRMS patients with shorter TL had a higher rate of converting to secondary progressive MS over a 10-year follow-up period.Implications of all the available evidenceAs we and others have shown, TL are generally shorter in MS patients and associated with disease progression, independent of age. These findings suggest a link between biological aging and the heterogeneous clinical course of MS patients. It currently remains unclear whether shortened telomeres in MS are a cause or a consequence of the pathophysiological processes. Further studies with larger patient cohorts and different cell populations will be needed to expand our knowledge of age-related disease mechanisms and the use of TL as a biomarker in MS.

scholarly journals Association Between Dietary Selenium Intake and Leukocyte Telomere Length in a Nationally Representative Sample of US Adults (OR11-06-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Buyun Liu ◽  
Yangbo Sun ◽  
Guifeng Xu ◽  
Shuang Rong ◽  
Wei Bao
Keyword(s):  
Telomere Length ◽  
Representative Sample ◽  
Quantitative Polymerase Chain Reaction ◽  
Antioxidant Properties ◽  
Biological Aging ◽  
Leukocyte Telomere Length ◽  
Telomere Shortening ◽  
Dietary Selenium ◽  
Selenium Intake ◽  
Nationally Representative

Abstract Objectives DNA damage induced by oxidative stress is implicated in accelerated telomere shortening, a biomarker of biological aging. Although selenium has antioxidant properties, its impact on telomere length is largely unknown. This study aimed to examine the association between dietary selenium intake and leukocyte telomere length in a nationally representative sample of US adults. Methods We included 7409 adults aged 20 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Dietary selenium intake was calculated using data collected in the 24-hour dietary recall. Leukocyte telomere length was assayed using the quantitative polymerase chain reaction method. The association between selenium intake and telomere length was estimated by weighted linear regression models adjusting for demographic, socioeconomic and lifestyle factors, body mass index, supplements intake, and leukocyte cell type composition. Results The average dietary selenium intake was 109.1 mg/d (standard error [SE] 1.15). We didn't find a significant association between dietary selenium intake and telomere length in US adults. The average telomere length (SE) was 1.01 (0.02), 1.01 (0.01), and 1.04 (0.01) across increasing tertiles of dietary selenium intake. However, a significant interaction was observed for age (P = 0.02). Among individuals aged 20–44 years, the β coefficient of log-transformed telomere length, compared to lowest tertile of dietary selenium intake, was −0.041 (SE 0.012, P = 0.002) and −0.033 (SE 0.018, P = 0.07) for middle tertile and the highest tertile of selenium intake, respectively. The corresponding β coefficient was 0.009 (SE 0.016, P = 0.59) and −0.001 (SE 0.012, P = 0.95), respectively, for adults 45–64 years old, and 0.017 (SE 0.015, P = 0.28) and 0.059 (SE 0.021, P = 0.01), respectively, for those aged 65 years or older. The results were not appreciably changed even after additionally adjustment for dietary intake of vitamin A, vitamin E, and zinc. Conclusions The association between dietary selenium intake and telomere length differed significantly by age groups, indicating that higher selenium intake may prevent telomere shortening in older adults but not in younger or middle-aged adults. Further studies about the underlying mechanisms are warranted. Funding Sources NA.

scholarly journals Telomere Length and Long-Term Endurance Exercise: Does Exercise Training Affect Biological Age? A Pilot Study

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52769 ◽  
Author(s):  
Ida Beate Ø. Østhus ◽  
Antonella Sgura ◽  
Francesco Berardinelli ◽  
Ingvild Vatten Alsnes ◽  
Eivind Brønstad ◽  
...  
Keyword(s):  
Pilot Study ◽  
Exercise Training ◽  
Telomere Length ◽  
Endurance Exercise ◽  
Biological Age

Telomere shortening velocity of patients administered with hypnotics is accelerated in a gender-differential manner

2020 ◽  
pp. 1-6
Author(s):  
Toyoki Maeda ◽  
Takahiko Horiuchi ◽  
Naoki Makino
Keyword(s):  
Telomere Length ◽  
The Other ◽  
Biological Aging ◽  
Shortening Velocity ◽  
Telomere Shortening ◽  
Female Patients ◽  
Associated Diseases ◽  
Other Hand ◽  
Male Patients ◽  
Gender Differential

The telomere length and its distribution were compared between patients administered with and without hypnotics to see if regular administration of hypnotics is associated with their aging-related somatic telomere shortening. Male patients presented significant shortening of telomere length of circulating leukocytes in association with age (–41.9 bp/year, p = 0.045) in contrast with controls (–18.3 kb/year, p = 0.155). On the other hand, female patients presented no significant shortening of telomere length with aging (–16.4 bp/year, p = 0.372) in contrast with controls (–55.9 bp/year, p = 0.00005). These results suggested that regular administration of hypnotics is associated with aging progression in a gender-related manner. The administration of hypnotics could be an indicator as the somatic aging status and for the screening of background lifestyle-associated diseases promoting biological aging.

Premature Aging of Hematopoietic Cells in Long Term Survivors after HSCT with Chronic GVHD and a Female Donor.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 829-829 ◽  
Author(s):  
Gabriela M. Baerlocher ◽  
Alicia Rovo ◽  
Astrid Mueller ◽  
Sybille Matthey ◽  
Martin Stern ◽  
...  
Keyword(s):  
Telomere Length ◽  
Chronic Gvhd ◽  
Nkt Cells ◽  
Premature Aging ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Female Donor ◽  
The Mean ◽  
Long Term Survivors

Abstract The establishment of donor-derived hematopoiesis in recipients of hematopoietic stem cell (HSC) transplantation (HSCT) involves extensive proliferation of HSCs and might lead to “premature aging” of hematopoietic cells. Telomere shortening as indicator of cell proliferation has been described after HSCT. The telomere attrition has mainly been observed during the first year after allogeneic HSCT. Thereafter, telomere length dynamics of recipients appeared not to differ from their donors. The aim of our cross-sectional study was to evaluate the telomere attrition in leukocyte subsets of very long term survivors (LTS) after HSCT in relation to donor/recipient age, sex, cell counts in peripheral blood, number of transplanted nucleated cells (NTNC), and occurrence of acute and chronic graft versus host disease (GVHD). Automated multicolour flow-FISH was used to measure the telomere length in granulocytes, naive T-cells, B-cells and NK/NKT-cells of 44 LTS and their HLA-identical sibling donors. At HSCT the median age of donors and recipients was 25.8 (2–46) and 26.8 years (5–50). The median follow-up after HSCT was 17.5 years (11–26). Four patients received HSCT for aplastic anemia, 40 for hematological malignancies. All patients received bone marrow as source of HSC and TBI was part of the conditioning in 39 (89%). Acute GVHD was observed in 31 (70%), and chronic GVHD in 22 (50%) patients. The age-matched and cell-type specific absolute telomere length values for recipients and donors fell between the 1st-99th percentile of the normal distribution. The telomere length (mean ± std) was significantly shorter in recipients as compared to their donors (p<0.01) for granulocytes (6.5±0.9 vs 7.1±0.9), T-cells (5.7±1.2 vs 6.6±1.2), B-cells (7.1±1.1 vs 7.8±1.1) and NK/NKT-cells (4.8±1.0 vs 5.6±1.3). The mean difference between recipients and donors for each subset of cells was between 0.6–0.9 kb. The mean telomere length of all subsets of cells was significantly shorter for males compared to females even though this difference was small. Age, sex of recipient, NTNC, and acute GVHD had no impact on telomere attrition. In all cell types except NK/NKT-cells we found a significant telomere shortening in recipients transplanted with a female donor (p<0.04) and in those with chronic GVHD (p<0.04). The telomere length difference between donor/recipient was most pronounced for recipients with the combination of a female donor and chronic GVHD (Figure 1). The loss in telomere length is more than twice for patients with a female donor and chronic GVHD compared to those with a male donor without chronic GVHD. In summary, our data reveal chronic GVHD and a female donor to be predictors for higher telomere attrition in LTS after HSCT. The more pronounced telomere attrition with a female donor and chronic GVHD corresponds to approximately 30–60 years of cell aging and raises once more the question of cellular immuno-senescence and its consequences in LTS of HSCT. Figure Figure

scholarly journals Prolonged Glucocorticoid Exposure Does Not Accelerate Telomere Shortening in Cultured Human Fibroblasts

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1425
Author(s):  
Anthony S. Zannas ◽  
Oksana Kosyk ◽  
Calvin S. Leung
Keyword(s):  
Telomere Length ◽  
Psychosocial Stress ◽  
Prolonged Exposure ◽  
Disease Risk ◽  
Human Fibroblasts ◽  
Stress Hormones ◽  
In Vivo Studies ◽  
Biological Aging ◽  
Telomere Shortening

Psychosocial stress, especially when chronic or excessive, can increase disease risk and accelerate biological aging. Although the underlying mechanisms are unclear, in vivo studies have associated exposure to stress and glucocorticoid stress hormones with shorter telomere length. However, the extent to which prolonged glucocorticoid exposure can shorten telomeres in controlled experimental settings remains unknown. Using a well-characterized cell line of human fibroblasts that undergo gradual telomere shortening during serial passaging in culture, we show that prolonged exposure (up to 51 days) to either naturalistic levels of the human endogenous glucocorticoid cortisol or the more potent synthetic glucocorticoid dexamethasone is not sufficient to accelerate telomere shortening. While our findings await extension in other cell types and biological contexts, they indicate that the in vivo association of psychosocial stress with telomere shortening is unlikely to be mediated by a direct and universal glucocorticoid effect on telomere length.

Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication

Blood ◽  
2004 ◽  
Vol 103 (12) ◽  
pp. 4440-4448 ◽  
Author(s):  
Loretta Gammaitoni ◽  
Katja C. Weisel ◽  
Monica Gunetti ◽  
Kai-Da Wu ◽  
Stefania Bruno ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Telomere Length ◽  
Severe Combined Immunodeficiency ◽  
Telomerase Activity ◽  
Clinical Value ◽  
Telomere Shortening ◽  
Cd34 Cells

Abstract Telomerase activity, telomere length, stem/progenitor cell production, and function of CD34+ cells from cord blood (CB), bone marrow, and mobilized peripheral blood were evaluated in long-term cultures. CB cells were cultured either on OP-9 stromal cells transduced with an adenovector expressing thrombopoietin (TPO) or stimulated by a cytokine cocktail in the absence of stroma, with, in one method, CD34+ cells reisolated at monthly intervals for passage. Continuous expansion of stem cells as measured by in vitro cobblestone area and secondary colony-forming assays was noted for 18 to 20 weeks and by severe combined immunodeficiency (SCID)-repopulating cells (SRCs), capable of repopulating and serially passage in nonobese diabetic/SCID mice, for 16 weeks. Despite this extensive proliferation, telomere length initially increased and only at late stages of culture was evidence of telomere shortening noted. This telomere stabilization correlated with maintenance of high levels of telomerase activity in the CD34+ cell population for prolonged periods of culture. Cytokine-stimulated cultures of adult CD34+ cells showed CD34+ and SRC expansion (6-fold) for only 3 to 4 weeks with telomere shortening and low levels of telomerase. There is clearly a clinical value for a system that provides extensive stem cell expansion without concomitant telomere erosion. (Blood. 2004;103:4440-4448)

Long-Term Coculture of Adult Human Healthy Donor CD34+ Cells Shows Elevation of Telomeres in a Subgroup of Donors Independent of Age, Stem Cell Function and Telomerase Activity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1695-1695
Author(s):  
Katja C. Weisel ◽  
Kaida Wu ◽  
Lothar Kanz ◽  
Malcolm A.S. Moore
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Telomere Length ◽  
Healthy Donor ◽  
Progenitor Cell ◽  
Telomerase Activity ◽  
Suspension Cells ◽  
Telomere Shortening ◽  
Cd34 Cells

Abstract Long-term cytokine-supplemented or stromal cocultures of human CD34+ cells, particularly from cord blood (CB), show expansion of hematopoietic progenitors and stem cells. Ultimately, however cultures decline and terminally differentiate. Despite upregulation of telomerase activity in proliferating primitive hematopoietic cells, telomere shortening has generally been reported in long-term cultures of CB, bone marrow or G-CSF mobilized peripheral blood CD34+ cells. In earlier reports, we described a long-term culture of hematopoietic stem cells on a murine OP9 bone marrow stroma cell line transfected with an adenovector expressing thrombopoietin, which allowed an extensive proliferation and self-renewal of CB CD34+ cells for 4–5 months with sustained elevation of telomerase activity and without concomitant significant telomere shortening (Blood, 2004). Here, we evaluated adult healthy donor peripheral blood (PB) CD34+ cells in the same OP9/Tpo coculture system. To determine progenitor and stem cell production, standard CFC and 2ndry cobblestone area-forming cell assays (CAFC assayed at 5 weeks on MS5 stroma) were undertaken weekly with suspension cells. In addition telomere length was measured by telomere restriction fragment (TRF) assay, and telomerase activity by TRAP assay on input CD34+ cells, and weekly on culture suspension cells. Maximum total cell, CFC and CAFC production was seen in the first 4 weeks with up to 80-fold expansion in cell count, up to 4-fold expansion in CFC and up to 13-fold expansion in CAFC. Thereafter a continuous decrease in production of cells, CFC 2ndry CAFC was observed and cultures terminated at week 8. Mean telomere length of input PB CD34+ cells was 9,5 ± 0,5 kbp. After 4 weeks in culture, telomere length remained stable (9,6 ± 0,5 kbp). In 3/6 cultures terminated, cultures showed only a slightly decrease of telomere length compared to the input population (0,55 ± 0,1 kbp loss). However, in 2/6 cultures we could demonstrate an elevation of telomeres (+ 0,3 kbp) independent of a rapid loss of telomerase activity in all cultures during the culture period. Furthermore, the elevation of telomeres did not correlate with an enhanced stem/progenitor cell activity. These data confirm earlier results of granulocyte telomere change in myeloma patients following chemotherapy and tandem transplantation, where 154/193 patients showed an expected loss of telomeres during the treatment period, whereas 39/193 patients had an unexpected elevation of telomeres. We could now show in healthy donors that this phenomenon is independent of bone marrow stress due to chemotherapeutic treatment. In conclusion, we could show that the stromal coculture system with OP9/Tpo is highly effective in stem/progenitor cell expansion not only in CB but also in PB CD34+ cells. It is the first culture system, which allows expansion of hematpoietic cells without significant telomere erosion. We furthermore describe for the first time an age-independent healthy donor population which shows telomerase-independent, significant telomere elevation. Further studies have to demonstrate, if this phenomenon is potentially linked to a higher susceptibility for cancer disease.

Differences in telomere length between patients with bipolar disorder and controls are influenced by lithium treatment

2020 ◽  
Vol 21 (8) ◽  
pp. 533-540 ◽  
Author(s):  
Claudia Pisanu ◽  
Donatella Congiu ◽  
Mirko Manchia ◽  
Paola Caria ◽  
Cristina Cocco ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Telomere Length ◽  
Lithium Treatment ◽  
Telomere Shortening ◽  
Genome Wide ◽  
History Of ◽  
Genetically Determined ◽  
The Relationship

Aim: To assess the role of lithium treatment in the relationship between bipolar disorder (BD) and leukocyte telomere length (LTL). Materials & methods: We compared LTL between 131 patients with BD, with or without a history of lithium treatment, and 336 controls. We tested the association between genetically determined LTL and BD in two large genome-wide association datasets. Results: Patients with BD with a history lithium treatment showed longer LTL compared with never-treated patients (p = 0.015), and similar LTL compared with controls. Patients never treated with lithium showed shorter LTL compared with controls (p = 0.029). Mendelian randomization analysis showed no association between BD and genetically determined LTL. Conclusion: Our data support previous findings showing that long-term lithium treatment might protect against telomere shortening.

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