scholarly journals Progressive Telomere Shortening in Aplastic Anemia

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3582-3592 ◽  
Author(s):  
Sarah E. Ball ◽  
Frances M. Gibson ◽  
Siân Rizzo ◽  
Jennifer A. Tooze ◽  
Judith C.W. Marsh ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Late Complication ◽  
Blood Leukocytes ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Age Related ◽  
High Incidence ◽  
Telomere Loss ◽  
Cell Fractions ◽  
Telomere Erosion

Abstract Improved survival in aplastic anemia (AA) has shown a high incidence of late clonal marrow disorders. To investigate whether accelerated senescence of hematopoietic stem cells might underlie the pathophysiology of myelodysplasia (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late complication of AA, we studied mean telomere length (TRF) in peripheral blood leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with normal controls. TRF lengths in the patient group were significantly shorter for age than normals (P < .0001). Telomere shortening was apparent in both granulocyte and mononuclear cell fractions, suggesting loss at the level of the hematopoietic stem cell. In patients with acquired AA with persistent cytopenias (n = 40), there was significant correlation between telomere loss and disease duration (r = −.685; P < .0001), equivalent to progressive telomere erosion at 216 bp/yr, in addition to the normal age-related loss. In patients who had achieved normal full blood counts (n = 20), the rate of telomere loss had apparently stabilised. There was no apparent association between telomere loss and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less than 5.0 kb, 3 had acquired cytogenetic abnormalities, suggesting that telomere erosion may be relevant to the pathogenesis of MDS in aplastic anemia.

scholarly journals Progressive Telomere Shortening in Aplastic Anemia

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3582-3592 ◽  
Author(s):  
Sarah E. Ball ◽  
Frances M. Gibson ◽  
Siân Rizzo ◽  
Jennifer A. Tooze ◽  
Judith C.W. Marsh ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Late Complication ◽  
Blood Leukocytes ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Age Related ◽  
High Incidence ◽  
Telomere Loss ◽  
Cell Fractions ◽  
Telomere Erosion

Improved survival in aplastic anemia (AA) has shown a high incidence of late clonal marrow disorders. To investigate whether accelerated senescence of hematopoietic stem cells might underlie the pathophysiology of myelodysplasia (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late complication of AA, we studied mean telomere length (TRF) in peripheral blood leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with normal controls. TRF lengths in the patient group were significantly shorter for age than normals (P < .0001). Telomere shortening was apparent in both granulocyte and mononuclear cell fractions, suggesting loss at the level of the hematopoietic stem cell. In patients with acquired AA with persistent cytopenias (n = 40), there was significant correlation between telomere loss and disease duration (r = −.685; P < .0001), equivalent to progressive telomere erosion at 216 bp/yr, in addition to the normal age-related loss. In patients who had achieved normal full blood counts (n = 20), the rate of telomere loss had apparently stabilised. There was no apparent association between telomere loss and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less than 5.0 kb, 3 had acquired cytogenetic abnormalities, suggesting that telomere erosion may be relevant to the pathogenesis of MDS in aplastic anemia.

Telomere Length of Peripheral Blood Leukocytes Predicts Relapse and Clonal Evolution after Immunosuppressive Therapy in Severe Aplastic Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 442-442 ◽  
Author(s):  
James N Cooper ◽  
Rodrigo Calado ◽  
Colin Wu ◽  
Phillip Scheinberg ◽  
Neal Young
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Aplastic Anemia ◽  
Telomere Length ◽  
Peripheral Blood ◽  
Copy Number ◽  
Clonal Evolution ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Hematopoietic Stem

Abstract Severe aplastic anemia (SAA) can be treated with either immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT). Response to IST depends on control of the immune response and on a hematopoietic stem cell (HSC) compartment capable of repopulating the bone marrow after therapy. Telomeres are protective repetitive DNA sequences at the ends of chromosomes; telomeres shorten with each cell division due to DNA polymerase deficiency to fully duplicate telomeric ends. Cells with critically shortened telomeres undergo proliferative senescence, apoptosis, and genomic instability. Excessive shortening of telomeres has been proposed as a potential biomarker for HSC exhaustion, and loss-of-function mutations in telomerase genes cause excessive telomere erosion and associate with marrow failure. To test the hypothesis that telomere length is a predictor of successful outcome after IST in SAA, telomere length of peripheral blood leukocytes were measured by quantitative PCR and expressed as the relative ratio of telomere repeat copy number to single gene copy number (T/S ratio) in 168 consecutive patients prior to IST therapy. The cohort consisted of patients with SAA (mean age, 34 years; range, 4–82) enrolled in three sequential protocols at the National Institutes of Health from 2003 to 2008 (ClinicalTrials.gov identifiers, NCT00001964, NCT00260689, and NCT00061360); all patients received IST based on horse anti-thymoglobulin (h-ATG) plus cyclosporine (CsA). Additional treatments depended on specific protocol arm: mycophenolate mofetil (32 patients), rabbit-ATG in place of h-ATG (31 patients), or rapamycin (35 patients); 70 patients received h-ATG and CsA only. None of the patients had clinical findings suggestive of dyskeratosis congenita. All adult patients or legal guardians signed informed consent according to NHLBI Institutional Review Board. Response, relapse, and clonal evolution rates were similar across all regimens. Using both a univariate and multivariate Cox regression model, telomere length was not associated with response (partial or complete) to IST at 6 months. However, for patients who initially responded to therapy, telomere length as a continuous variable inversely correlated with relapse rate (P=0.01). When telomere length was treated as a categorical variable, patients with shorter telomeres (below the 50th percentile of telomere distribution) had 2.5 times higher probability to relapse in five years then did patients with longer telomeres (P=0.002). Since telomere length physiologically shortens with aging, patients were stratified as being either greater than or equal/less than fifty years old to address whether shortened telomeres were a surrogate marker of age. In patients over 50 only (n=54), short telomere length but not age predicted relapse (P =0.04) in a multivariate model including telomere length, age, and pre-treatment blood counts, indicating that telomere length associated with relapse independently of age. Approximately 10% of patients undergoing IST eventually develop secondary clonal evolution. In this cohort 11/168 patients developed cytogenetic abnormalities, myelodysplastic syndrome, or leukemia in 5 years, and telomere length inversely correlated with risk for clonal evolution (P=0.01). These results indicate that leukocytes’ telomere length predicts sustained response to IST, possibly serving as a biological marker for HSC reserve. While initial response to treatment results from reducing cytotoxic T-cells, patients with short telomeres may quickly reach a critical length threshold where further stem cell division is not possible. Patients in this cohort with the shortest telomeres also were at risk for developing clonal evolution.

scholarly journals Telomere in Aging and Age-Related Diseases

2017 ◽  
Vol 9 (3) ◽  
pp. 113
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Inflammatory Diseases ◽  
Human Diseases ◽  
Economic Stability ◽  
Telomere Shortening ◽  
Age Related ◽  
Associated Proteins ◽  
Telomere Biology ◽  
Multiple Chronic Diseases ◽  
Huge Challenge ◽  
Telomere Erosion

BACKGROUND: The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span.CONTENT: Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic instability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases’ pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications.SUMMARY: Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management.KEYWORDS: telomerase, cellular senescence, aging, cancer

Comprehensive Analysis of Telomere Biology in Patients with Aplastic Anemia and Hypoplastic Myelodysplastic Syndrome: Further Evidence for a Common Mechanism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2858-2858
Author(s):  
Anne-Sophie Bouillon ◽  
Monica S. Ferreira ◽  
Benjamin Werner ◽  
Sebastian Hummel ◽  
Jens P. Panse ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Common Mechanism ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Bone Marrow Failure Syndromes ◽  
The Individual

Abstract Introduction: Acquired aplastic anemia (AA) is typically characterized by pancytopenia and bone marrow (BM) failure mostly due to an autoimmune attack against the hematopoietic stem cell compartment. Thus, AA patients frequently respond to immunosuppressive therapy (IST). Hypoplastic myelodysplastic syndrome (hMDS) frequently mimics clinical and morphological features of AA and proper clinical discrimination of hMDS from AA sometimes remains difficult. Interestingly, some cases of hMDS respond at least partially to IST and on the other hand, AA can clonally evolve to hMDS. Telomeres shorten with each cell division and telomere length (TL) reflects the replicative potential of somatic cells. Whereas it is proposed that TL can to some degree discriminate hereditary subtypes of bone marrow failure syndromes from classical acquired forms, the role of TL for disease pathogenesis in hMDS remains unclear. In this study, we therefore aimed to investigate accelerated TL shortening as a possible (bio-)marker to distinguish hMDS from AA. Patients and Methods: TL of BM biopsies at diagnosis of 12 patients with hMDS and 15 patients with AA treated in the University Hospital Düsseldorf were analyzed. Mean age was 45.2 years in AA patients and 65.2 years in patients with hMDS. Confocal Q-FISH protocol was used for TL measurement as published previously (Blood, 2012). TL analysis was performed in single-blinded fashion. 28 patients (range 18-80 years) with newly diagnosed M. Hodgkin without BM affection were used as controls for linear regression and calculation of age-adapted TL difference. For the analysis of the data, we made use of a recently developed mathematical model of TL distribution on the stem cell level allowing us to extrapolate mean TL shortening per year (TS/y) based on the individual TL distributions of captured BM biopsies. Results: Using the controls to adjust for age, we found that age-adapted TL was significantly shortened both in patients with AA (median: -2.96 kb, range -4.21 to 0.26, p=0.001) and patients with hMDS (median: -2.26, range -3.85 to -0.64, p=0.005). In direct comparison, telomere shortening was more accelerated in patients with AA as compared to hMDS (p=0.048). Next, we analyzed the TL shortening per year (TS/y) based on the individual telomere distribution. Calculating the extrapolated TL shortening per year (TS/y), we found significant increased TS/y in AA patients (mean±SD: 235,8 bp/y±202,9, p=0.001) and hMDS patients (120,5±41,7 bp/y, p=0.0001) compared to controls (37,5±18,9 bp/y). Interestingly, the extrapolated rate of TS/y remained stable at different ages in hMDS patients as observed in healthy controls. In contrast, TS/y in AA patients showed a strong age-dependence with a maximum of TS/y in patients younger than 30 years (R²=0.42, p=0.008). Finally, we set to test whether TS/y can be used to identify AA or hMDS patients. Using 150 bp TS/y as a cut-off (4-fold the mean of controls), we found significantly more AA patients (10/15, 66.7%) had accelerated TL shortening compared to hMDS (1/12, 8.3% p=0.005). Conclusion: We provide first retrospective data on TL in patients with hMDS using confocal Q-FISH. Age-adapted TL is significantly shorter in patients with AA compared to hMDS. Interestingly, telomere shortening per year is both significantly increased in AA as compared to hMDS patients as well as in both groups compared to controls. The rate of telomere shortening TS/y might represent a new marker in patients with bone marrow failure syndromes that allows to discriminate AA from hMDS patients pending prospective validation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Telomere maintenance and human bone marrow failure

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4446-4455 ◽  
Author(s):  
Rodrigo T. Calado ◽  
Neal S. Young
Keyword(s):  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Genetic Diseases ◽  
Telomerase Activity ◽  
Dyskeratosis Congenita ◽  
Telomere Maintenance ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Telomere Binding Protein ◽  
Genes Encoding

AbstractAcquired and congenital aplastic anemias recently have been linked molecularly and pathophysiologically by abnormal telomere maintenance. Telomeres are repeated nucleotide sequences that cap the ends of chromosomes and protect them from damage. Telomeres are eroded with cell division, but in hematopoietic stem cells, maintenance of their length is mediated by telomerase. Accelerated telomere shortening is virtually universal in dyskeratosis congenita, caused by mutations in genes encoding components of telomerase or telomere-binding protein (TERT, TERC, DKC1, NOP10, or TINF2). About one-third of patients with acquired aplastic anemia also have short telomeres, which in some cases associate with TERT or TERC mutations. These mutations cause low telomerase activity, accelerated telomere shortening, and diminished proliferative capacity of hematopoietic progenitors. As in other genetic diseases, additional environmental, genetic, and epigenetic modifiers must contribute to telomere erosion and ultimately to disease phenotype. Short telomeres also may cause genomic instability and malignant progression in these marrow failure syndromes. Identification of short telomeres has potential clinical implications: it may be useful in dyskeratosis congenita diagnosis, in suggesting mutations in patients with acquired aplastic anemia, and for selection of suitable hematopoietic stem cell family donors for transplantation in telomerase-deficient patients.

Severe telomere shortening in patients with paroxysmal nocturnal hemoglobinuria affects both GPI– and GPI+ hematopoiesis

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 514-516 ◽  
Author(s):  
Anastasios Karadimitris ◽  
David J. Araten ◽  
Lucio Luzzatto ◽  
Rosario Notaro
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Aplastic Anemia ◽  
Distinctive Feature ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Epigenetic Change ◽  
Telomere Shortening ◽  
Hematopoietic Stem ◽  
Cell Divisions ◽  
History Of

Abstract A most distinctive feature of paroxysmal nocturnal hemoglobinuria (PNH) is that in each patient glycosylphosphatidylinositol-negative (GPI–) and GPI+ hematopoietic stem cells (HSCs) coexist, and both contribute to hematopoiesis. Telomere size correlates inversely with the cell division history of HSCs. In 10 patients with hemolytic PNH the telomeres in sorted GPI– granulocytes were shorter than in sorted GPI+ granulocytes in 4 cases, comparable in 2 cases, and longer in the remaining 4 cases. Furthermore, the telomeres of both GPI– and GPI+ hematopoietic cells were markedly shortened compared with age-matched controls. The short telomeres in the GPI– cells probably reflect the large number of cell divisions required for the progeny of a single cell to contribute a large proportion of hematopoiesis. The short telomeres of the GPI+ cells indicate that the residual hematopoiesis contributed by these cells is not normal. This epigenetic change is an additional feature shared by PNH and aplastic anemia.

scholarly journals Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 89 ◽  
Author(s):  
Christian Bär ◽  
Maria A. Blasco
Keyword(s):  
Environmental Factors ◽  
Telomere Length ◽  
Therapeutic Targets ◽  
Therapeutic Strategies ◽  
Telomere Shortening ◽  
Age Related ◽  
Human Telomere ◽  
Linear Chromosomes ◽  
Telomere Erosion

Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself.

scholarly journals Telomere Shortening in Kidneys with Age

2000 ◽  
Vol 11 (3) ◽  
pp. 444-453 ◽  
Author(s):  
ANETTE MELK ◽  
VIDO RAMASSAR ◽  
LISA M. H. HELMS ◽  
RON MOORE ◽  
DAVID RAYNER ◽  
...  
Keyword(s):  
Southern Blotting ◽  
Replicative Senescence ◽  
Regression Line ◽  
Dependent Manner ◽  
Telomere Shortening ◽  
Paired Samples ◽  
Age Related ◽  
Telomere Loss ◽  
Renal Aging

Abstract. The histology and function of the kidney deteriorates with age and age-related diseases, but the mechanisms involved in renal aging are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stresses that increase replication. This study explored the relationship between age and telomere length in surgical samples from 24 human kidneys, which were either histologically normal (17) or displayed histologic abnormalities (7). Telomere loss was assessed by two independent methods: Southern blotting of terminal restriction fragments (TRF) and slot blotting using telomere-specific probes. The results of these methods correlated with each other. The mean TRF length determined by Southern blotting in cortex was about 12 kb pairs (kbp) in infancy and was shorter in older kidneys. The slope of the regression line was about 0.029 kbp (0.24%, P = 0.023) per year. Telomere DNA loss in cortex by the slot blot method was 0.25% per year (P = 0.011). By both methods, the telomere loss in medulla was not significant and was less than in cortex. Comparisons of TRF length from 20 paired samples from cortex and medulla showed that TRF was greater in cortex than medulla, with the differences being greater in young kidneys and lessening with age due to telomere loss in cortex. These findings indicate that telomeres shorten in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal cortex.

scholarly journals Increased Age-Related B-Cells in Patients with Aplastic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5099-5099
Author(s):  
Elena E. Solomou ◽  
Eva Plakoula ◽  
Argiris Symeonidis ◽  
Athanasios Galanopoulos ◽  
Athina Vyniou ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
B Cells ◽  
Aplastic Anemia ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Number Of Patients ◽  
Stimulation Of

Abstract Increased Age-Related B-cells in Patients with Aplastic Anemia Introduction: Aplastic anemia is a rare disease characterized by immune dysregulation. T cells in aplastic anemia are characterized by various intrinsic defects leading to increased IFN-g levels and Fas-mediated apoptosis of hematopoietic stem cells. We and others, have previously shown that the transcription factor T-bet is over-expressed in T cells from patients with aplastic anemia. Recently it was shown that a subpopulation of B cells also express T-bet; these cells are characterized as age-related B cells (ABCs) and express high levels of CD11c and CD19, they are CD21 negative and express T-bet. These T-bet+ ABCs are found increased in patients with autoimmune diseases (i.e. systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis). Stimulation of B cells with antigens, Toll-like receptors and IFN-g leads to the formation of ABCs, which in turn "talk" to the T cells and stimulate them. Stimulation of T cells leads to IFN-g production, and this IFN-g may lead to further induction of T-bet expressing B cells (ABCs). Specific aim: In this study we wanted to examine the expression of ABCs in patients with aplastic anemia. We isolated peripheral blood mononuclear cells (PBMCs) from patients with aplastic anemia (n=10) and eight healthy, age- matched controls. Written informed consent was obtained from all study subjects. Cells were stained with the surface markers CD11c, CD19 and CD21, and subsequently analyzed using flow cytometry. An anti-Tbet antibody was also used after cell permeabilization. The CD11c-high, CD19 positive, CD21 negative, T-bet positive population represent the ABCs. Results: Patients with aplastic anemia at presentation showed increased numbers of circulating ABCs compared to healthy controls (29,08±1,62% vs 4,06 ±0,4 % respectively, p<0.001).(Fig. 1). Patients who responded to treatment showed comparable levels of ABCs to those of healthy individuals (5,93±0,6% vs 4,06 ±0,4 % respectively). Non-responders had statistically significant increased levels of ABCs compared to healthy controls (p<0,001). Also, non-responders had ABCs levels similar to those of aplastic anemia patients at presentation (29,08±1,62% vs 31,7 ±2,97 % respectively, p=0,44). Conclusion: Although the number of patients analyzed is limited, our preliminary results suggest that aplastic anemia patients show expanded ABCs compared to age-matched control subjects, and these numbers are related to disease status. Further analysis of a larger pool of subjects is underway along with the examination of the specific transcription factor Bcl-6, that is implicated in T-bet expression in ABCs. These results will reveal the role of ABCs in the immune pathogenesis of aplastic anemia. Figure 1. Figure 1. Disclosures Kattamis: CELGENE: Consultancy, Honoraria; Vifor Pharma: Consultancy; Novartis: Consultancy, Honoraria; ApoPharma: Honoraria.

scholarly journals Association of accelerated dynamics of telomere sequence loss in peripheral blood leukocytes with incident knee osteoarthritis in Osteoarthritis Initiative cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebeca Guillén ◽  
Fátima Otero ◽  
Alejandro Mosquera ◽  
María Vázquez-Mosquera ◽  
Ignacio Rego-Pérez ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Joint Disease ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Knee Oa ◽  
Age Related ◽  
Telomere Sequence ◽  
Osteoarthritis Initiative ◽  
Telomere Loss

AbstractOsteoarthritis (OA) is a chronic degenerative joint disease, being the main cause of laboral inability. Decreased telomere size in peripheral blood leukocytes (PBL) has been correlated with age-related pathologies, like knee OA. In a dynamic approach, telomere-qPCR was performed to evaluate the relative percentage of PBL telomere loss after a 6-year follow-up, in 281 subjects from the prospective osteoarthritis initiative (OAI) cohort. A radiological Kellgren-Lawrence (KL) grade ≥ 2 was indicative of knee OA. Individuals with knee OA at recruitment (n = 144) showed a higher PBL telomere loss after 6 years than those without knee OA at baseline (n = 137; p = 0.018). Moreover, individuals that developed knee OA during the follow-up (n = 39) exhibited a higher telomere loss compared to those that remained without OA (n = 98; p < 0.001). Logistic regression analysis showed that PBLs telomere loss was not significantly associated with knee OA at recruitment, but behaves as an independent risk factor associated with incidence after follow-up (OR: 1.043; p = 0.041), together with maximum KL grade (OR: 3.627; p = 0.011), body mass index-BMI (OR: 1.252; p < 0.001) and WOMAC-index (OR: 1.247; p = 0.021), at recruitment. The telomere decay in PBLs is faster in individuals with incident knee OA, possibly reflecting a systemic-global accelerated aging that enhances the cartilage degeneration.

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