A percentage analysis of the telomere length in Parkinson's disease patients

Telomeres are the repeated sequences at the chromosome ends which undergo shortening with cell division. The telomere shortening of the peripheral leukocytes is also facilitated by enhanced oxidative stress in various kinds of disease including ischemic heart disease, diabetes mellitus, apoplexy, and Alzheimer's disease. Telomere shortening in Parkinson's disease (PD) has not yet been reported. The pathogenesis for PD is also regarded to be associated with oxidative stress. We investigated 28 Japanese male PD patients ages 47-69. Although we could not find a statistical difference in the mean telomere length of peripheral leukocytes between the PD patients and the control participants, we found the mean telomere lengths to be shorter than 5 kb in only the PD patients and a significant PD-associated decrease in the telomeres with a length ranging from 23.1 to 9.4 kb in the patients in their 50s and 60s. These observations suggest that telomere shortening is accelerated in PD patients in comparison to the normal population.     

Telomere shortening in atherosclerosis

Eukaryotic chromosomes end with telomeres, which shorten with cellular ageing. We investigated whether atherosclerosis is associated with systemic evidence of accelerated cellular ageing. We compared mean length of terminal restriction fragments (TRF), a measure of average telomere size, in leucocyte DNA of ten patients with severe coronary artery disease (CAD) with that of 20 controls without CAD. Adjusting for age and sex, cases had mean TRF lengths of 303 (SD 90) base pairs shorter than those of controls (p=0.002)-ie, equivalent in size to individuals with no CAD who are 8.6 years older. Although this is a pilot study, the findings could be relevant to the pathogenesis of atherosclerosis.     

Telomeric DNA length in cerebral gray and white matter is associated with longevity in individuals aged 70 years or older

Many studies have demonstrated the association between telomere length in mitotic cells and carcinogenesis and mortality, but little attention has been focused on post-mitotic cells and human life expectancy. We assessed the relationship between telomere length in cerebral gray and white matter and longevity in 72 autopsied Japanese patients aged 0-100 years using Southern blot hybridization. The mean telomere lengths in the gray and white matter were 12.3+/-2.5 kilobase pairs and 11.4+/-2.1 kilobase pairs, respectively. The mean telomere lengths in 60-69 year decadal group were less than those of neonates, and declined further in the 70-79-year age group, but those in groups of further advanced age were longer than in the 70-79 year group (70-79<80-89<90-100 years of age). Thus, the 90-100-year age group possessed significantly longer telomeres than the 70s (p=0.029). Autopsy protocols showed a decrease in the rate of cancer death in individuals in their 80s (p=0.041) and 90s (p=0.017) versus those in their 60s, and in their 80s the mean telomere length in the gray matter from cancer death patients was significantly shorter than that of patients who died of other diseases (p=0.04). These data suggest that innate telomere lengths are maintained very well in the cerebrum, and are associated with longevity. Our study lends indispensable support to the hypothesis that longer telomeres protect the genome from instability (a major cause of carcinogenesis) and are beneficial for longevity.     

Telomere length dynamics in the human pituitary gland: robust preservation throughout adult life to centenarian age

Many studies have demonstrated the association between telomere length in mitotic cells and aging, but the relationship between telomere length in post-mitotic cells and aging in human populations has remained largely unclear. In this study, we assessed the dynamics of telomere length (terminal restriction fragment length—TRF) in normal pituitary glands obtained at autopsy from 65 patients aged between 0 and 100 years. The initial length (the value for neonatal pituitary) was 14.2 ± 1.1 kbp (mean of the median TRF value ± SD), being the longest among those for other systemic organs. The annual telomere reduction rates for pituitary (21 bp) were equivalent to or below the lowest values for various cells and tissues. Hence, comparison of TRF lengths among organs revealed that the pituitary gland retained longer telomeres than most other organs throughout life. The median TRF value showed a significant decrease between newborns and the 61–75 age group, but then leveled off or increased slightly in advanced age groups. These data indicate that innate telomere length is highly conserved in the pituitary and suggest that pituitary telomere length provides a good basic indicator for studies of telomere biology.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-011-9280-y) contains supplementary material, which is available to authorized users.     

Accelerated telomere shortening and telomerase activation in Fanconi's anaemia

Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by progressive bone marrow failure that often evolves towards acute leukaemia. FA also belongs to a group of chromosome instability diseases. Because telomeres are directly involved in chromosomal stability and in cell proliferation capacity, we examined telomere metabolism in peripheral blood mononuclear cells (PBMC). Telomere length was significantly shorter in 54 FA patient samples, compared to 51 controls (P<0.0001). In addition, mean telomere terminal restriction fragment lengths (TRF) in nine heterozygous patient samples did not differ from those of controls. In 14 samples from FA patients with severe aplastic anaemia (SFA), telomere length was significantly shorter than in 22 samples of age-matched FA patients with moderate haematological abnormalities (NSFA) (P<0.001). However, no correlation was found between TRF length and the presence of bone marrow clonal abnormalities in 16 additional, separately analysed, patient samples. Sequential measurement of TRF in six FA patients showed an accelerated rate of telomere shortening. Accordingly, telomere shortening rate was inversely correlated with clinical status. Telomerase, the enzyme that counteracts telomere shortening, was 4.8-fold more active in 25 FA patients than in 15 age-matched healthy controls. A model for the FA disease process is proposed.     

Aldosterone and telomere length in white blood cells

BACKGROUND: Aldosterone accelerates cardiovascular aging by mechanisms that generate reactive oxygen species. Telomere length in white blood cells (WBCs) may be a bioindicator that registers the accruing burden of systemic oxidative stress. The aim of the present study was, therefore, to examine the relationship between plasma aldosterone and telomere length in WBCs. METHODS: We studied 75 normotensive and never-treated mildly hypertensive men whose blood was drawn for the measurements of plasma aldosterone concentration and the terminal restriction fragment (TRF) length in WBCs. RESULTS: The slope of the TRF-age relationship in the entire cohort showed a decrease in telomere length of 26 +/- 5 base pairs per year (r = -0.46, p <.001). Age-adjusted TRF length was the longest in the lowest aldosterone quartile (6.74 +/- 0.12 kb) and shortest in the highest aldosterone quartile (6.36 +/- 0.11 kb), with intermediate TRF lengths in the second and third aldosterone quartiles (analysis of variance [ANOVA] trend test, p =.025). In telomeric attrition equivalence, participants in the upper aldosterone quartile were 15 years older than their peers in the lowest quartile. CONCLUSIONS: The inverse relationship between aldosterone and WBC telomere length suggests not only that aldosterone is pro-oxidant but that elevated concentrations of this hormone might be linked to a higher rate of telomere attrition and perhaps increased biological aging in humans.     

Telomere shortening occurs in Asian Indian Type 2 diabetic patients.

AIM: Telomere shortening has been reported in several diseases including atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection for Type 2 diabetes and premature coronary artery disease. The aim of this study was to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic patients. METHODS: Using Southern-blot analysis we determined mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leucocyte DNA. Type 2 diabetic patients without any diabetes-related complications (n = 40) and age- and sex-matched control non-diabetic subjects (n = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence method. RESULTS: Mean (+/- SE) TRF lengths of the Type 2 diabetic patients (6.01 +/- 0.2 kb) were significantly shorter than those of the control subjects (9.11 +/- 0.6 kb) (P = 0.0001). Among the biochemical parameters, only levels of TBARS showed a negative correlation with shortened telomeres in the diabetic subjects (r = -0.36; P = 0.02). However, telomere lengths were negatively correlated with insulin resistance (HOMA-IR) (r = -0.4; P = 0.01) and age (r = -0.3; P = 0.058) and positively correlated with HDL levels (r = 0.4; P = 0.01) in the control subjects. Multiple linear regression (MLR) analysis revealed diabetes to be significantly (P < 0.0001) associated with shortening of TRF lengths. CONCLUSIONS: Telomere shortening occurs in Asian Indian Type 2 diabetic patients.     

Telomere length in myelodysplastic syndromes

We have studied telomere length in the bone marrow cells or the granulocyte and lymphocyte cell fractions of 54 patients with myelodysplastic syndromes (MDS) by Southern blot hybridization using the (TTAGGG)₄ probe. The average telomere length expressed as the peak telomere repeat array (TRA) in the peripheral blood, or bone marrow samples obtained from a group of 21 healthy age-matched controls (26–89 years old, mean age 55), ranged between 7.5 and 9.5 kb (mean peak TRA 8.6 kb). Twenty-four patients with refractory anemia (RA) were studied; 10/24 (42%) had telomere reduction (<7.5 kb) relative to age-matched controls and the mean peak TRA was 7.5 kb (range 4.0–9.0 kb). Eleven patients with RA with excess blasts (RAEB) were studied; 5/11 (45%) had reduced telomeres relative to age-matched controls and the mean peak TRA was 7.1 kb (range 5.0–9.0 kb). Eighteen patients with MDS in transformation to AML, comprising 15 with RAEB in transformation (RAEBt) and 3 with CMML in transformation (CMMLt), were also studied. Thirteen of eighteen patients (72%) had telomere reduction relative to age-matched controls and the mean peak TRA was 6.1 kb (range 3.5–9.0 kb). Thirty-six patients included in the study had either a normal karyotype or a simple karyotype (1 karyotypic change) and 20/36 (55%) of these had telomere reduction and the mean peak TRA was 7.1 kb (range 4.3–9.0 kb); 8 patients had a complex karyotype (3 or more karyotypic changes) and 5/8 (62%) of these had telomere reduction and the mean peak TRA was 6.1 kb (range 3.5–9.0 kb). We conclude, firstly that there is heterogeneity of telomere length in MDS and that this is observed throughout the spectrum of FAB-subtypes. Secondly, these data show that a marked reduction in telomere length in MDS if often associated with leukemic transformation and with the presence of complex karyotypic abnormalities. Am. J. Hematol. 56:266–271, 1997. © 1997 Wiley-Liss, Inc.     

Accelerated in vivo epidermal telomere loss in Werner syndrome

Many data pertaining to the accelerated telomere loss in cultured cells derived from Werner syndrome (WS), a representative premature aging syndrome, have been accumulated. However, there have been no definitive data on in vivo telomere shortening in WS patients. In the present study, we measured terminal restriction fragment (TRF) lengths of 10 skin samples collected from extremities of 8 WS patients aged between 30 and 61 years that had been surgically amputated because of skin ulceration, and estimated the annual telomere loss. Whereas the values of TRF length in younger WS patients (in their thirties) were within the normal range, those in older WS patients were markedly shorter relative to non‐WS controls. Regression analyses indicated that the TRF length in WS was significantly shorter than that in controls (p < 0.001). Furthermore, we found that TRF lengths in muscle adjacent to the examined epidermis were also significantly shorter than those of controls (p = 0.047). These data demonstrate for the first time that in vivo telomere loss is accelerated in systemic organs of WS patients, suggesting that abnormal telomere erosion is one of the major causes of early onset of age‐related symptoms and a predisposition to sarcoma and carcinoma in WS.     

Telomere length and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study

Short telomeres are associated with aging and age-related diseases. Our aim was to determine whether short leukocyte telomere length is associated with risk factors and cardiovascular diseases in a high-risk hypertensive population. We measured leukocyte telomere lengths at recruitment in 1271 subjects with hypertension and left ventricular hypertrophy (LVH) participating in the Lifestyle Interventions and Independence for Elders (LIFE) study. At baseline, short mean telomere length was associated with coronary artery disease in males (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.39-0.95), and transient ischemic attack in females (OR 0.62 95% CI 0.39-0.99). Proportion of short telomeres (shorter than 5?kb) was associated with Framingham risk score (r=0.07, P<0.05), cerebrovascular disease (OR 1.18, 95% CI 1.01-1.15) and type 2 diabetes in men (OR 1.07, 95% CI 1.02-1.11). During follow-up, proportion of short telomeres was associated with combined cardiovascular mortality, stroke or angina pectoris (hazard ratio 1.04, 95% CI 1.01-1.07). Telomere length was not associated with smoking, body mass index, pulse pressure or self-reported use of alcohol. Our data suggest that reduced leukocyte telomere length is associated with cardiovascular risk factors and diseases as well as type 2 diabetes, and is a predictor of cardiovascular disease in elderly patients with hypertension and LVH.     

Constitution and telomere dynamics of bone marrow stromal cells in patients undergoing allogeneic bone marrow transplantation

We evaluated the genotypic origin of mesenchymal stem cells (MSC) following sex-mismatched allogeneic bone marrow transplantation (BMT), and investigated the telomere dynamics in MSC in normal individuals and patients after BMT. The study population consisted of 11 patients with hematologic disorders who showed complete chimerism after BMT. Telomere length was measured in MSC using Southern blotting analysis in eight patients and 18 healthy subjects as a control group. Following culture, MSC were identified by the expression of SH2 and SH4, and lack of CD14, CD34, and CD45. All MSC showed the recipient genotype, based on the results of fluorescent in situ hybridization analysis using X-chromosome satellite probes or microsatellite DNA polymorphism analysis. The mean telomere length in MSC from normal controls was 7.2+/-0.53 kb (range, 6.12-7.78), and progressive telomere shortening was seen with age. There was no significant difference in MSC telomere length between the BMT group and age-matched controls. This study confirmed that the MSC isolated from the recipients of allogeneic BMT did not have the donor genotype, despite complete chimerism. Moreover, MSC were demonstrated to show progressive loss of telomere length with age, but the telomeres in MSC were not affected by BMT.     

Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation

Telomere length of peripheral blood mononuclear cells (PBMCs) from 23 autologous HSCT patients ranging from 4 to 61 years old, and 46 allogeneic HSCT recipients from 6 to 52 years old were studied to confirm whether excessive shortening of telomeres is associated with HSCT. After autologous HSCT, telomere length of PBMCs ranged from 6.8 to 12.0 kb. The comparison between transplanted PBMCs and PBMCs after autologous HSCT showed shortening by up to 1.9 kb (mean +/- s.d.: 0.64 +/- 0.50 kb). There was a difference between autologous HSCT patients and normal volunteers in the slopes of regression lines. After allogeneic HSCT, telomere length of PBMCs ranged from 6.8 to 12.0 kb. Telomeres of recipients were up to 2.1 kb (0.60 +/- 0.468 kb) shorter than those of donors. The slope of regression lines for allogeneic HSCT patients and normal volunteers were parallel. Although all patients were transplanted with more than 2.0 x 10(8) cells/kg, telomere length did not correlate with the number of transplanted cells. There was no significant correlation between telomere length and recovery of hematological parameters. However, three patients with an average telomere length of 6.8 kb after HSCT took a longer period to reach the normal hematological state. Taken together, these data suggest that most HSCTs are performed within the biological safety range of telomeres, while the patients who have telomeres shorter than 7.0 kb after HSCT should be observed carefully for long-term hematopoiesis and the occurrence of hematopoietic disorders.     

Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders

In this study we investigated telomere restriction fragment (TRF) length in a panel of mature B-cell lymphoproliferative disorders (MBCLDs) and correlated this parameter with histology and histopathogenesis in relation to the germinal center (GC). We assessed 123 MBCLD samples containing 80% or more tumor cells. TRF length was evaluated by Southern blot analysis using a chemiluminescence-based assay. GC status was assessed through screening for stable and ongoing somatic mutations within the immunoglobulin heavy-chain genes. Median TRF length was 6170 bp (range, 1896-11 200 bp) and did not correlate with patient age or sex. TRF length was greater in diffuse large cell lymphoma, Burkitt lymphoma, and follicular lymphoma (medians: 7789 bp, 9471 bp, and 7383 bp, respectively) than in mantle cell lymphoma and chronic lymphocytic leukemia (medians: 3582 bp and 4346 bp, respectively). GC-derived MBCLDs had the longest telomeres, whereas those arising from GC-inexperienced cells had the shortest (P < 10(-9)). We conclude that (1) TRF length in MBCLD is highly heterogeneous; (2) GC-derived tumors have long telomeres, suggesting that minimal telomere erosion occurs during GC-derived lymphomagenesis; and (3) the short TRF lengths of GC-inexperienced MBCLDs indicates that these neoplasms are good candidates for treatment with telomerase inhibitors, a class of molecules currently the subject of extensive preclinical evaluation.     

Telomere length regulation in mice is linked to a novel chromosome locus

Little is known about the mechanisms that regulate species-specific telomere length, particularly in mammalian species. The genetic regulation of telomere length was therefore investigated by using two inter-fertile species of mice, which differ in their telomere length. Mus musculus (telomere length >25 kb) and Mus spretus (telomere length 5–15 kb) were used to generate F1 crosses and reciprocal backcrosses, which were then analyzed for regulation of telomere length. This analysis indicated that a dominant and trans-acting mechanism exists capable of extensive elongation of telomeres in somatic cells after fusion of parental germline cells with discrepant telomere lengths. A genome wide screen of interspecific crosses, using M. spretus as the recurrent parent, identified a 5-centimorgan region on distal chromosome 2 that predominantly controls the observed species-specific telomere length regulation. This locus is distinct from candidate genes encoding known telomere-binding proteins or telomerase components. These results demonstrate that an unidentified gene(s) mapped to distal chromosome 2 regulates telomere length in the mouse.     

Conserved nucleoprotein structure at the ends of vertebrate and invertebrate chromosomes.

Eukaryotic chromosomes terminate with telomeres, nucleoprotein structures that are essential for chromosome stability. Vertebrate telomeres consist of terminal DNA tracts of sequence (TTAGGG)n, which in rat are predominantly organized into nucleosomes regularly spaced by 157 bp. To test the hypothesis that telomeres of other animals have nucleosomes, we compared telomeres from eight vertebrate tissues and cell cultures, as well as two tissues from an invertebrate. All telomeres have substantial tracts of (TTAGGG)n comprising 0.01-0.2% of the genome. All telomeres are long (20-100 kb), except for those of sea urchin, human, and some chicken chromosomes, which are 3-10 kb in length. All of the animal telomeres contained nucleosome arrays, consistent with the original hypothesis. The telomere repeat lengths vary from 151 to 205 bp, seemingly uncorrelated with telomere size, regularity of nucleosome spacing, species, or state of differentiation but surprisingly correlated with the repeat of bulk chromatin within the same cells. The telomere nucleosomes were consistently approximately 40 bp smaller than bulk nucleosomes. Thus, animal telomeres have highly conserved sequences and unusually short nucleosomes with cell-specific structure.     

Telomere length is age-dependent and reduced in monocytes of Alzheimer patients

Telomeres are regions of repetitive DNA at the end of eukaryotic chromosomes, which prevent chromosomal instability. Telomere shortening is linked to age-related disease including Alzheimer's disease (AD) and has been reported to be reduced in leukocytes of AD patients. The aim of the present study was to measure telomere length in monocytes of patients with AD or mild cognitive impairment (MCI) compared to healthy subjects. Our data show significant shorter telomere length in AD patients (6.6±0.2kb; p=0.05) compared to controls (7.3±0.2kb). Telomere length of MCI patients did not differ compared to healthy subjects (7.0±0.2kb). We observe a strong correlation between telomere length and age (p=0.01, r=-0.38), but no association between telomere length and Mini-Mental State Examination score. In conclusion, the telomere length is age-dependent in monocytes and decreased in AD patients, which could mean that the AD pathology may contribute to telomere length shortening. The high variability of telomere lengths in individuals suggests that it will not be useful as a general biomarker for AD. However, it could become a biomarker in personalized long-term monitoring of an individuals' health.     

Telomere shortening in patients with plasma cell disorders

OBJECTIVES: Telomeres are essential for maintaining chromosomal integrity; their shortening is associated with chromosome instability. The aim of this work was to study telomere length (TL) on bone marrow (BM) cells from patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). METHODS: Thirty-one MM patients: 12 at diagnosis (D), 11 at relapse (R) and eight at remission (RE) and two cases with MGUS were studied. TL based on terminal restriction fragment (TRF) assay was evaluated. Cytogenetic and molecular cytogenetic analyses were performed. Telomeric associations (TAs) on BM metaphases were also studied. RESULTS: TRF analysis in total MM patients showed a mean TRF peak value (5.20 +/- 0.35 kb) shorter than those observed in controls (8.5 +/- 0.5 kb) (P < 0.001). Moreover, TRF at D and R showed a significant telomere shortening (P < 0.001), with TL restored at RE. A strong correlation with the percentage of BM plasma cell infiltration (BMPCI) (rK = -0.540; P = 0.002) was found. Patients with abnormal karyotypes (AK) had significantly shorter TRFs than that observed in MM patients with normal karyotypes (P < 0.05). TRFs in MGUS patients did not differ with respect to controls. TA analysis showed an increased percentage in MM (19.46 +/- 1.98%) with respect to MGUS (6.12 +/- 1.87%) and normal BM cells (2.00 +/- 0.93%) (P < 0.001). CONCLUSIONS: MM patients showed a significant reduction in TL (> 60% of BMPCI and AK), suggesting a probable association with clinical evolution. Moreover, our findings support the idea that telomere shortening usually leads to increased frequencies of TAs and chromosome instability.     

Telomere length changes in patients undergoing hematopoietic stem cell transplantation.

Telomere length indicates the replicative history of cells, serving as a molecular measure of the replicative potential remaining in cells. To investigate telomere length changes in hematopoietic stem cells, patients undergoing hematopoietic stem cell transplantation (HSCT) were evaluated. Fifteen patients after allogeneic bone marrow transplantation (allo-BMT group), seven patients after autologous peripheral blood stem cell transplantation (auto-PBSCT group), and 39 healthy controls were studied. Telomere length was measured in peripheral mononuclear cells by Southern blot hybridization. There was no significant difference between the allo-BMT and the auto-PBSCT groups. In the allo-BMT group, the mean telomere length of recipients was 2.01 kb shorter than that of their donors (P = 0. 008), and was 1.59 kb shorter than that of age-matched putative normal controls (P = 0.002). Telomere shortening in the allo-BMT group was equivalent to 41.4 years of aging in the donors, and to 52. 4 years of aging in the normal controls. The mean telomere length in the auto-PBSCT group was 2.36 kb shorter than that of the age-matched putative controls (P = 0.043), which was equivalent to 61.5 years of aging in normal controls. The extent of telomere shortening in the allo-BMT group showed a trend to negative correlation with the number of mononuclear cells infused. These findings suggest that hematopoietic stem cells after HSCT lose telomere length and these shortened telomeres may result in a higher incidence of clonal disorders later in life.     

The distribution and accumulation of the shortest telomeres in telomere biology disorders

Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the ‘telomere brink’ at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence. We used the Telomere Shortest Length Assay (TeSLA) to tally TL of all 46 chromosomes in blood-derived DNA and examined its relationship with TBDs. Patients (n = 18) had much shorter mean TL (TeSmTL) (2.54 ± 0.41 kb vs. 4.48 ± 0.52 kb, p < 0.0001) and more telomeres <3 kb than controls (n = 22) (70.43 ± 8.76% vs. 33.05 ± 6.93%, p < 0.0001). The proportion of ultrashort telomeres (<1.6 kb) was also higher in patients than controls (39.29 ± 10.69% vs. 10.40 ± 4.09%, p < 0.0001). TeS <1.6 kb was associated with severe (n = 11) compared with non-severe (n = 7) BMF (p = 0.027). Patients with multi-organ manifestations (n = 10) had more telomeres <1.6 kb than those with one affected organ system (n = 8) (p = 0.029). Findings suggest that TBD clinical manifestations are associated with a disproportionately higher number of haematopoietic cell telomeres reaching a telomere brink, whose length at the single telomere level is yet to be determined.     

Telomere length inversely correlates with pulse pressure and is highly familial

There is evidence that telomeres, the ends of chromosomes, serve as clocks that pace cellular aging in vitro and in vivo. In industrialized nations, pulse pressure rises with age, and it might serve as a phenotype of biological aging of the vasculature. We therefore conducted a twin study to investigate the relation between telomere length in white blood cells and pulse pressure while simultaneously assessing the role of genetic factors in determining telomere length. We measured by Southern blot analysis the mean length of the terminal restriction fragments (TRF) in white blood cells of 49 twin pairs from the Danish Twin Register and assessed the relations of blood pressure parameters with TRF. TRF length showed an inverse relation with pulse pressure. Both TRF length and pulse pressure were highly familial. We conclude that telomere length, which is under genetic control, might play a role in mechanisms that regulate pulse pressure, including vascular aging.