Changes In Relative Telomere Length Research Articles

Differential Effect of 2 Hormonal Contraceptives on the Relative Telomere Length of Youth With Type 1 Diabetes.

Adolescents and young women (AYA) with type 1 diabetes (T1D) may require hormonal contraception for an extended period. However, it is unclear what effect hormonal contraception has on telomere length, a marker of the risk for complications. To investigate the relative telomere length (RTL) in AYA with T1D (AYA-T1D) and healthy young women (AYA-C) after 18 months of combined oral contraception use (COC) with ethinyl estradiol/desogestrel, or a subdermal etonogestrel implant (IM). A nonrandomized prospective study was performed in which 39 AYA-T1D and 40 AYA-C chose the COC or the IM. RTL was measured by monochrome multiplex-quantitative PCR in DNA from peripheral blood mononuclear cells (PBMC). The impact of contraceptives and clinical variables on RTL was assessed using lineal regression analysis. Longer RTL compared to baseline was observed in AYA-T1D (P < .05) and AYA-C (P < .01) after using the IM. However, the total of AYA and the AYA-C group treated with COC decreased RTL after 18 months of treatment compared to baseline (P < .05). The type of contraceptive used was determinant for the changes in RTL compared to baseline in all subjects and controls (P ≤ .006). For AYA-T1D, HbA1c levels were not associated with RTL, but the high-sensitivity C-reactive protein was negatively related with the changes in RTL at 18 months compared to baseline (standardized R2 : 0.230, P = .003). IM was associated with longer RTL in AYA-T1D and AYA-C. In contrast, a shortening of telomere length in PBMC was observed after using COC.

Greater physiological resistance to heat may favour an invasive freshwater turtle, enabling it to outcompete native species in a changing climate

Abstract Climate warming and biological invasion can interact to affect ecosystems, and the results of such interactions depend on whether invaders show physiological advantages in their responses to warming environments as compared with native species after the establishment and local adaptation. However, it has rarely been evaluated. The present study compared the heat tolerance of a globally invasive turtle, the red‐eared slider Trachemys scripta elegans, and two co‐occurring native turtle species in China, the Chinese soft‐shelled turtle Pelodiscus sinensis and Chinese pond turtle Mauremys reevesii, after acclimation in the same thermal environment. The expression patterns of heat shock factor 1 (HSF1), multiple heat shock proteins (HSPs) and telomere reverse transcriptase (TERT), and changes in relative telomere length (RTL) were then evaluated in liver and muscle of turtles under thermal stress. The results showed that T. scripta elegans had greater physiological resistance to heat than the co‐occurring native turtle species, and that this higher tolerance was accompanied by a higher temperature induction of the peak expression of inducible HSPs in liver and a higher onset temperature for the main inducible HSPs in muscle. During thermal stress, T. scripta elegans showed a better ability to maintain the expression levels of TERT under extremely hot conditions, whereas high temperatures inhibited TERT in muscles of native turtle species. Meanwhile, thermal stress did not cause telomere erosion in any of the three turtle species and some treatments can lead to slightly longer telomeres in T. scripta elegans or M. reevesii. Overall, the invasive turtle species showed higher heat tolerance and physiological advantages in enduring hot weather in comparison to the co‐occurring native turtle species. This may favour these invaders in situations of climate warming. Our study highlights the role of physiological adaptations displayed by invaders in achieving advantages over native species under climate change.

Temperature-independent telomere lengthening with age in the long-lived human fish (Proteus anguinus).

Despite a number of studies showing a negative relationship between age and telomere length, the universality of this pattern has been recently challenged, mainly in ectothermic animals exhibiting diverse effects of age on telomere shortening. However, data on ectotherms may be strongly affected by the thermal history of the individuals. We thus investigated the age-related changes in relative telomere length in the skin of a small but long-lived amphibian living naturally in a stable thermal environment over its entire life, allowing comparison with other homeothermic animals like birds and mammals. The present data showed a positive relation between telomere length and individual age, independent of sex and body size. A segmented analysis highlighted a breakpoint in the telomere length-age relationship, suggesting that telomere length reached a plateau at the age of 25 years. Further studies focusing on the biology of animals that live much longer than expected based on body mass will contribute to our better understanding of how ageing processes evolved and may also bring innovation for extending human health span.

Changes in Relative Telomere Length in Patients with Obstructive Sleep Apnea Syndrome on the Background of CPAP Therapy: A Pilot Study

Changes in Relative Telomere Length in Patients with Obstructive Sleep Apnea Syndrome on the Background of CPAP Therapy: A Pilot Study

Three months-longitudinal changes in relative telomere length, blood chemistries, and self-report questionnaires in meditation practitioners compared to novice individuals during midlife.

Aging accelerates during midlife. Researches have shown the health benefits of mind-body intervention (MBI). However, whether MBI is involved with aging process has not been well understood. In this study, we approach to examine the relations of MBI with this process by investigating an aging marker of the peripheral blood, blood chemistry, and self-report questionnaires. A quasi-experimental design was applied. Experienced MBI practitioners participated in a 3-month intensive meditation training, while the age, gender-matched MBI-naïve controls led a normal daily life. Measurements were taken at before and after the 3 months for relative telomere length (RTL), blood chemistry, and self-report questionnaires including items about sleep quality, somatic symptoms, depression, anxiety, stress, emotional intelligence (EI), and self-regulation. For RTL, the repeated measures analysis of variance showed a significant group*time interaction (P = .013) with a significant post hoc result (P = .030) within the control group: RTL was significantly reduced in the control while it was maintained in the meditation group. In repeated measures analysis of variance for blood chemistries, there were significant group differences between the groups in glucose and total protein. In the post hoc comparison analysis, at post measurements, the meditation group exhibited significantly lower values than the control group in both glucose and total protein. There were significant group-wise differences in the correlations of RTL with triglyceride (TG), high-density lipoprotein (HDL), glutamic oxaloacetic transaminase and glutamic pyruvic transaminase. Any of self-report results did not show significant changes in group*time interaction. However, there were group differences with significant (P < .05) or a tendency (.05 < P < .1) level. There were significant improvements in depression, stress and EI as well as tendencies of improvement in sleep quality and anxiety, in the meditation group compared to the control group. Our results suggest that meditation practice may have a potential to modify aging process in molecular cellular level combined with changes in psychological dimension.

Telomerase activity, relative telomere length, and longevity in alfalfa (Medicago sativa L.)

Background Medicago sativa L. ‘Qingshui’ is a valuable rhizomatous forage germplasm resource. We previously crossed Qingshui with the high-yielding Medicago sativa L. ‘WL168’ and obtained novel rhizomatous hybrid strains (RSA-01, RSA-02, and RSA-03). Telomere dynamics are more accurate predictors of survival and mortality than chronological age. Based on telomere analyses, we aimed to identify alfalfa varieties with increased stamina and longevity for the establishment of artificial grazing grasslands. Methods In this study, we performed longitudinal analysis of telomerase activity and relative telomere length in five alfalfa varieties (Qingshui, WL168, RSA-01, RSA-02, and RSA-03) at the age of 1 year and 5 years to examine the relationship among telomerase activity, rate of change in relative telomere length, and longevity. We further aimed to evaluate the longevity of the examined varieties. Telomerase activity and relative telomere length were measured using enzyme-linked immunosorbent assay and real-time polymerase chain reaction, respectively. Results We observed significant differences in telomerase activity between plants aged 1 year and those aged 5 years in all varieties except WL168, and the rate of change in telomerase activity does not differ reliably with age. As telomerase activity and relative telomere length are complex phenomena, further studies examining the molecular mechanisms of telomere-related proteins are needed. Relative telomere lengths of Qingshui, WL168, RSA-01, RSA-02, and RSA-03 in plants aged 5 years were higher than those aged 1 year by 11.41, 11.24, 9.21, 10.23, and 11.41, respectively. Relative telomere length of alfalfa tended to increase with age. Accordingly, alfalfa varieties can be classified according to rate of change in relative telomere length as long-lived (Qingshui, WL168, and RSA-03), medium-lived (RSA-02) and short-lived (RSA-01). The differences in relative telomere length distances of Qingshui, WL168, RSA-01, RSA-02, and RSA-03 between plants aged 1 and 5 years were 10.40, 13.02, 12.22, 11.22, and 13.25, respectively. The largest difference in relative telomere length was found between Qingshui and RSA-02 at 2.20. Our findings demonstrated that relative telomere length in alfalfa is influenced by genetic variation and age, with age exerting a greater effect.

Cascading Effects of Conspecific Aggression on Oxidative Status and Telomere Length in Zebra Finches.

Living in social groups may exacerbate interindividual competition for territory, food, and mates, leading to stress and possible health consequences. Unfavorable social contexts have been shown to elevate glucocorticoid levels (often used as biomarkers of individual stress), but the downstream consequences of socially stressful environments are rarely explored. Our study experimentally tests the mechanistic links between social aggression, oxidative stress, and somatic maintenance in captive zebra finches (Taeniopygia guttata). Over 64 d, we measured the effects of aggression (received or emitted) on the individual oxidative status, body condition, and changes in relative telomere length (rTL) of birds living in high- and low-social-density conditions. Using path analyses, we found that birds living at high social density increased their aggressive behavior. Birds receiving the highest number of aggressions exhibited the strongest activation of antioxidant defenses and highest plasmatic levels of reactive oxygen metabolites. In turn, this prevented birds from maintaining or restoring telomere length between the beginning and the end of the experiment. Received aggression also had a direct negative effect on changes in rTL, unrelated to oxidative stress. In contrast, emitted aggression had no significant effect on individual oxidative stress or changes in rTL. Body condition did not appear to affect the physiological response to aggression or oxidative stress. At low density, we found trends that were similar to those at high density but nonsignificant. Our study sheds light on the causal chain linking the social environment and aggressive behavior to individual oxidative stress and telomere length. The long-term consequences of socially induced stress on fitness remain to be characterized.

Relative Telomere Length Change in Colorectal Carcinoma and Its Association with Tumor Characteristics, Gene Expression and Microsatellite Instability.

Simple SummaryTelomeres are specialized repeat DNA sequences at the ends of each chromosome. The primary function of telomeres is to prevent genomic instability. Telomeres shorten with every cell division. The role of relative telomere length (RTL) change in colorectal cancer (CRC) is not fully understood. We studied RTL in CRC tissue and adjacent normal tissue from the same patients (n = 165). We found significant shortening of RTL in cancer tissue, irrespective of age group, gender, tumor pathology, location and microsatellite instability (MSI) status. However, shortening was more pronounced in low-grade tumors and in the presence of MSI. Gene expression data suggested an association of telomere shortening with rapid cell division (upregulation of DNA replication and cyclin-dependent kinase genes), as well as downregulation of apoptosis genes. CRC tissue showed upregulation of some telomere maintenance genes.We compared tumor and adjacent normal tissue samples from 165 colorectal carcinoma (CRC) patients to study change in relative telomere length (RTL) and its association with different histological and molecular features. To measure RTL, we used a Luminex-based assay. We observed shorter RTL in the CRC tissue compared to paired normal tissue (RTL 0.722 ± SD 0.277 vs. 0.809 ± SD 0.242, p = 0.00012). This magnitude of RTL shortening (by ~0.08) in tumor tissue is equivalent to RTL shortening seen in human leukocytes over 10 years of aging measured by the same assay. RTL was shorter in cancer tissue, irrespective of age group, gender, tumor pathology, location and microsatellite instability (MSI) status. RTL shortening was more prominent in low-grade CRC and in the presence of microsatellite instability (MSI). In a subset of patients, we also examined differential gene expression of (a) telomere-related genes, (b) genes in selected cancer-related pathways and (c) genes at the genome-wide level in CRC tissues to determine the association between gene expression and RTL changes. RTL shortening in CRC was associated with (a) upregulation of DNA replication genes, cyclin dependent-kinase genes (anti-tumor suppressor) and (b) downregulation of “caspase executor”, reducing apoptosis.

Tail loss and telomeres: consequences of large-scale tissue regeneration in a terrestrial ectotherm

Large-scale tissue regeneration has potential consequences for telomere length through increases in cell division and changes in metabolism which increase the potential for oxidative stress damage to telomeres. The effects of regeneration on telomere dynamics have been studied in fish and marine invertebrates, but the literature is scarce for terrestrial species. We experimentally induced tail autotomy in a lizard ( Niveoscincus ocellatus) and assessed relative telomere length (RTL) in blood samples before and after partial tail regeneration while concurrently measuring reactive oxygen species (ROS) levels. The change in ROS levels was a significant explanatory variable for the change in RTL over the 60-day experiment. At the average value of ROS change, the mean RTL increased significantly in the control group (intact tails), but there was no such evidence in the regenerating group. By contrast, ROS levels decreased significantly in the regenerating group, but there was no such evidence in the control group. Combined, these results suggest that tail regeneration following autotomy involves a response to oxidative stress and this potentially comes at a cost to telomere repair. This change in telomere maintenance demonstrates a potential long-term cost of tail regeneration beyond the regrowth of tissue itself.

Связь изменений относительной длины теломер в течение пятнадцати лет с маркерами возрастных изменений сердечно- сосудистой системы у лиц среднего возраста по результатам исследования питания и рака в Мальмё (Швеция)

Objective. To analyse the association between long-term changes in relative telomere length (RTL) and selected markers of cardiovascular ageing such as history of myocardial infarction (MI), pulse pressure or usage of antihypertensive (AHT) drugs during 15 years of follow-up. Subjects and methods. 332 middle-aged subjects were recruited from a population-based, case-control study of patients with MI. RTL in blood at baseline and after 15 years of follow-up was investigated through quantitative PCR. Z-statistics was used to compare the log-distribution of RTL at baseline and at follow-up, respectively. The difference ( Δ z-score) was calculated for each individual as a marker of relative change in telomere length over 15 years. Multiple regression analysis was used with Δ z-score as dependent variable, and age, sex, RTL at baseline, and clinical markers of cardiovascular ageing as independent variables. Results. We found that Δz-score of RTL was independently associated with both total (prevalent/incident) MI (p < 0.039) and usage of AHT drugs (p < 0.015) at baseline. Subjects with MI or on AHT drugs showed a greater reduction in the z-score for RTL during follow-up, implying a higher degree of telomere shortening. Conclusion. Changes in blood relative telomere attrition (RTL) is a potential marker of cardiovascular ageing, as illustrated by significant and independent associations between Δ z-score and prevalent/incident MI, as well as with base-line usage of antihypertensive drugs — a marker of longstanding hypertension in need of treatment.

Cell cycle-dependent and -independent telomere shortening accompanies murine brain aging.

Replication-based telomere shortening during lifetime is species- and tissue-specific, however, its impact on healthy aging is unclear. In particular, the contribution of telomere truncation to the aging process of the CNS, where replicative senescence alone fails to explain organ aging due to low to absent mitotic activity of intrinsic populations, is undefined. Here, we assessed changes in relative telomere length in non-replicative and replicative neural brain populations and telomerase activity as a function of aging in C57BL/6 mice. Telomeres in neural cells and sub-selected neurons shortened with aging in a cell cycle-dependent and -independent manner, with preponderance in replicative moieties, implying that proliferation accelerates, but is not prerequisite for telomere shortening. Consistent with this telomere erosion, telomerase activity and nuclear TERT protein were not induced with aging. Knockdown of the Rela subunit of NF-κB, which controls both telomerase enzyme and subcellular TERT protein allocation, did also not influence telomerase activity or telomere length, in spite of its naive up-regulation selectively under aging conditions. We conclude that telomere instability is intrinsic to physiological brain aging beyond cell replication, and appears to occur independently of a functional interplay with NF-κB, but rather as a failure to induce or relocate telomerase.

Effects of water, sanitation, handwashing, and nutritional interventions on telomere length among children in a cluster-randomized controlled trial in rural Bangladesh.

Shorter childhood telomere length (TL) and more rapid TL attrition are widely regarded as manifestations of stress. However, the potential effects of health interventions on child TL are unknown. We hypothesized that a water, sanitation, handwashing (WSH), and nutritional intervention would slow TL attrition during the first two years of life. In a trial in rural Bangladesh, we randomized geographical clusters of pregnant women into individual water treatment, sanitation, handwashing, nutrition, combined WSH, combined nutrition plus WSH (N + WSH), or control arms. We conducted a substudy enrolling children from the control arm and the N + WSH intervention arm. Participants and outcome assessors were not masked; analyses were masked. Relative TL was measured at 1 and 2 years after intervention, and the change in relative TL was reported. Analysis was intention-to-treat. Between May 2012 and July 2013, in the overall trial, we randomized 720 geographical clusters of 5551 pregnant women to a control or an intervention arm. In this substudy, after 1 year of intervention, we assessed a total of 662 children (341 intervention and 321 control) and 713 children after 2 years of intervention (383 intervention and 330 control). Children in the intervention arm had significantly shorter relative TL compared with controls after 1 year of intervention (difference −163 base pairs (bp), p=0.001). Between years 1 and 2, TL increased in the intervention arm (+76 bp) and decreased in the controls (−23 bp) (p=0.050). After 2 years, there was no difference between the arms (p=0.305). Our unexpected finding of increased telomere attrition during the first year of life in the intervention group suggests that rapid telomere attrition during this critical period could reflect the improved growth in the intervention group, rather than accumulated stress. Funded by The Bill and Melinda Gates Foundation. NCT01590095.

Early-Life Telomere Dynamics Differ between the Sexes and Predict Growth in the Barn Swallow (Hirundo rustica).

Telomeres are conserved DNA-protein structures at the termini of eukaryotic chromosomes which contribute to maintenance of genome integrity, and their shortening leads to cell senescence, with negative consequences for organismal functions. Because telomere erosion is influenced by extrinsic and endogenous factors, telomere dynamics may provide a mechanistic basis for evolutionary and physiological trade-offs. Yet, knowledge of fundamental aspects of telomere biology under natural selection regimes, including sex- and context-dependent variation in early-life, and the covariation between telomere dynamics and growth, is scant. In this study of barn swallows (Hirundo rustica) we investigated the sex-dependent telomere erosion during nestling period, and the covariation between relative telomere length and body and plumage growth. Finally, we tested whether any covariation between growth traits and relative telomere length depends on the social environment, as influenced by sibling sex ratio. Relative telomere length declined on average over the period of nestling maximal growth rate (between 7 and 16 days of age) and differently covaried with initial relative telomere length in either sex. The frequency distribution of changes in relative telomere length was bimodal, with most nestlings decreasing and some increasing relative telomere length, but none of the offspring traits predicted the a posteriori identified group to which individual nestlings belonged. Tail and wing length increased with relative telomere length, but more steeply in males than females, and this relationship held both at the within- and among-broods levels. Moreover, the increase in plumage phenotypic values was steeper when the sex ratio of an individual’s siblings was female-biased. Our study provides evidence for telomere shortening during early life according to subtly different dynamics in either sex. Furthermore, it shows that the positive covariation between growth and relative telomere length depends on sex as well as social environment, in terms of sibling sex ratio.

Late-born intermittently fasted juvenile garden dormice use torpor to grow and fatten prior to hibernation: consequences for ageing processes.

Torpor is thought to slow age-related processes and to sustain growth and fattening of young individuals. Energy allocation into these processes represents a challenge for juveniles, especially for those born late in the season. We tested the hypothesis that late-born juvenile garden dormice (Eliomys quercinus) fed ad libitum ('AL', n = 9) or intermittently fasted ('IF', n = 9) use short torpor bouts to enhance growth and fat accumulation to survive winter. IF juveniles displayed more frequent and longer torpor bouts, compared with AL individuals before hibernation. Torpor frequency correlated negatively with energy expenditure and water turnover. Hence, IF juveniles gained mass at the same rate, reached similar pre-hibernation fattening and displayed identical hibernating patterns and mass losses as AL animals. We found no group differences in relative telomere length (RTL), an indicator of ageing, during the period of highest summer mass gain, despite greater torpor use by IF juveniles. Percentage change in RTL was negatively associated with mean and total euthermic durations among all individuals during hibernation. We conclude that torpor use promotes fattening in late-born juvenile dormice prior to hibernation. Furthermore, we provided the first evidence for a functional link between time spent in euthermy and ageing processes over winter.

Seasonal variation in telomere length of a hibernating rodent

Small hibernating rodents have greater maximum lifespans and hence appear to age more slowly than similar-sized non-hibernators. We tested for a direct effect of hibernation on somatic maintenance and ageing by measuring seasonal changes in relative telomere length (RTL) in the edible dormouse Glis glis. Average RTL in our population did not change significantly over the hibernation season, and a regression model explaining individual variation in post-hibernation RTL suggested a significant negative effect of the reduction in body mass over the inactive hibernation period (an index of time spent euthermic), supporting the idea that torpor slows ageing. Over the active season, RTL on average decreased in sub-adults but increased in adults, supporting previous findings of greater telomere shortening at younger ages. Telomere length increase might also have been associated with reproduction, which occurred only in adults. Our study reveals how seasonal changes in physiological state influence the progress of life-history traits, such as somatic maintenance and ageing, in a small hibernating rodent.

Work-Related Exhaustion and Telomere Length: A Population-Based Study

BackgroundPsychological stress is suggested to accelerate the rate of biological aging. We investigated whether work-related exhaustion, an indicator of prolonged work stress, is associated with accelerated biological aging, as indicated by shorter leukocyte telomeres, that is, the DNA-protein complexes that cap chromosomal ends in cells.MethodsWe used data from a representative sample of the Finnish working-age population, the Health 2000 Study. Our sample consisted of 2911 men and women aged 30–64. Work-related exhaustion was assessed using the Maslach Burnout Inventory - General Survey. We determined relative leukocyte telomere length using a quantitative real-time polymerase chain reaction (PCR) -based method.ResultsAfter adjustment for age and sex, individuals with severe exhaustion had leukocyte telomeres on average 0.043 relative units shorter (standard error of the mean 0.016) than those with no exhaustion (p = 0.009). The association between exhaustion and relative telomere length remained significant after additional adjustment for marital and socioeconomic status, smoking, body mass index, and morbidities (adjusted difference 0.044 relative units, standard error of the mean 0.017, p = 0.008).ConclusionsThese data suggest that work-related exhaustion is related to the acceleration of the rate of biological aging. This hypothesis awaits confirmation in a prospective study measuring changes in relative telomere length over time.

Daily torpor is associated with telomere length change over winter in Djungarian hamsters

Ageing can progress at different rates according to an individual's physiological state. Natural hypothermia, including torpor and hibernation, is a common adaptation of small mammals to survive intermittent or seasonal declines in environmental conditions. In addition to allowing energy savings, hypothermia and torpor have been associated with retarded ageing and increased longevity. We tested the hypothesis that torpor use slows ageing by measuring changes in the relative telomere length (RTL) of Djungarian hamsters, Phodopus sungorus, a highly seasonal rodent using spontaneous daily torpor, over 180 days of exposure to a short-day photoperiod and warm (approx. 20°C) or cold (approx. 9°C) air temperatures. Multi-model inference showed that change in RTL within individuals was best explained by positive effects of frequency of torpor use, particularly at low body temperatures, as well as the change in body mass and initial RTL. Telomere dynamics have been linked to future survival and proposed as an index of rates of biological ageing. Our results therefore support the hypothesis that daily torpor is associated with physiological changes that increase somatic maintenance and slow the processes of ageing.

Rapid Telomere Loss in Hematopoietic Cells Associated with Development of t-MDS after Autologous Transplantation for Lymphoma.

Therapy-related MDS (t-MDS) is a lethal complication of autologous hematopoietic cell transplantation (HCT) for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Although t-MDS is known to result from damage to hematopoietic stem cells (HSC) from genotoxic cancer treatment, the sequential cellular and molecular changes leading to its development are not known. To better understand t-MDS pathogenesis we are conducting a prospective study of a cohort of patients undergoing autologous HCT for HL and NHL. Patients are followed longitudinally from pre-HCT to 5 yrs post-HCT, with serial collection of marrow and blood samples. We investigated whether development of t-MDS after HCT was associated with altered telomere dynamics in hematopoietic cells. Telomeres are non-coding sequences at ends of chromosomes. Telomere shortening may be associated with genetic instability and myeloid leukemogenesis, and could predispose to t-MDS after HCT. Telomere length was measured in peripheral blood (PB) samples from 8 patients from the cohort who developed t-MDS after HCT and 24 matched controls who did not develop t-MDS (3 controls per case: matched for primary diagnosis, age at HCT, race and length of follow-up). Samples were analyzed pre-HCT and at d100, 6 months, 1 yr and then annually post-HCT till development of t-MDS. PB cells were mixed with equal numbers of 1301 cells, as internal controls, and hybridized with a telomere PNA-FITC probe. Relative telomere length (RTL) values (ratio of telomere signal of PB sample and control 1301 cells) were determined by flow cytometry (FlowFISH). RTL values of lymphoid and myeloid cells, identified by scatter properties, were separately analyzed. The median PBSC CD34+ count (106/kg) for cases was 4.9 (2.6–17.4) and controls was 5.2 (2.1–33.5). Differences in RTL were seen at several time points in t-MDS cases and controls for total cell, lymphoid and myeloid cells, but were most marked in the myeloid cells. Patients developing t-MDS showed reduced RTL pre-HCT (myeloid RTL: cases=18.2±4.8, controls=27.2±2.8); an increase in RTL at d 100 (myeloid RTL for cases=31.4±4.6, controls=19.6±2.5, p=0.04); and progressive reduction in RTL subsequently (myeloid RTL at 3 years: cases= 9.7±4.1, controls=22.0±2.2). An increase in RTL from pre-BMT to d 100 was seen in t-MDS patients (+16.0) but not in controls (−8.2) (p=0.004). A fixed effect growth curve model fitted to the data from d100 to 3 years to examine the rate of change in RTLs over time revealed a sharp decline in RTL for cases (β per 100 days = −1.93 for myeloid cells), but no change in RTL over time for controls (β = 0.07) (p = 0.02). In summary, we observed severely altered telomere dynamics in hematopoietic cells from patients who develop t-MDS post-HCT, with an initial increase in telomere length followed by a very sharp rate of telomere attrition till development of t-MDS. The initial increase in telomere length may reflect a need for increased recruitment of fresh HSC, with longer telomeres, to achieve hematopoietic recovery post-HCT. Subsequent rapid attrition of telomere length may reflect increased hematopoietic cell proliferation associated with ineffective hematopoiesis characteristic of MDS or represent altered telomere regulation in damaged HSC. Altered telomere regulation and reduced telomere length may contribute to leukemic transformation of HSC in t-MDS.