Telomere shortening in somatic tissues largely reflects stem cell replication. Previous human studies of telomere attrition were predominantly conducted on leukocytes. However, findings in leukocytes cannot be generalized to other tissues. Here we measure telomere length in leukocytes, skeletal muscle, skin and subcutaneous fat of 87 adults (aged 19–77 years). Telomeres are longest in muscle and shortest in leukocytes, yet are strongly correlated between tissues. Notably, the rates of telomere shortening are similar in the four tissues. We infer from these findings that differences in telomere length between proliferative (blood and skin) and minimally proliferative tissues (muscle and fat) are established during early life, and that in adulthood, stem cells of the four tissues replicate at a similar rate.
A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.
In this protocol we describe a method to obtain telomere length parameters using Southern blots of terminal restriction fragments (TRFs). We use this approach primarily for epidemiological studies that examine leukocyte telomere length. However, the method can be adapted for telomere length measurements in other cells whose telomere lengths are within its detection boundaries. After extraction, DNA is inspected for integrity, digested, resolved by gel electrophoresis, transferred to a membrane, hybridized with labeled probes and exposed to X-ray film using chemiluminescence. Although precise and highly accurate, the method requires a considerable amount of DNA (3 μg per sample) and it measures both the canonical and noncanonical components of telomeres. The method also provides parameters of telomere length distribution in each DNA sample, which are useful in answering questions beyond those focusing on the mean length of telomeres in a given sample. A skilled technician can measure TRF length in ∼130 samples per week.
SummaryInsulin resistance and oxidative stress are associated with accelerated telomere attrition in leukocytes. Both are also implicated in the biology of aging and in aging-related disorders, including hypertension. We explored the relations of leukocyte telomere length, expressed by terminal restriction fragment (TRF) length, with insulin resistance, oxidative stress and hypertension. We measured leukocyte TRF length in 327 Caucasian men with a mean age of 62.2 years (range 40 -89 years) from the Offspring cohort of the Framingham Heart Study. TRF length was inversely correlated with age ( r = -0.41, P < 0.0001) and age-adjusted TRF length was inversely correlated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ( r = -0.16, P = 0.007) and urinary 8-epi-PGF 2 α α α α ( r = -0.16, P = 0.005) -an index of systemic oxidative stress. Compared with their normotensive peers, hypertensive subjects exhibited shorter age-adjusted TRF length (hypertensives = 5.93 ± ± ± ± 0.042 kb, normotensives = 6.07 ± ± ± ± 0.040 kb, P = 0.025). Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance.
We have developed a low noise cantilever deflection sensor with a deflection noise density of 17fm∕Hz by optimizing the parameters used in optical beam deflection (OBD) method. Using this sensor, we have developed a multienvironment frequency-modulation atomic force microscope (FM-AFM) that can achieve true molecular resolution in various environments such as in moderate vacuum, air, and liquid. The low noise characteristic of the deflection sensor makes it possible to obtain a maximum frequency sensitivity limited by the thermal Brownian motion of the cantilever in every environment. In this paper, the major noise sources in OBD method are discussed in both theoretical and experimental aspects. The excellent noise performance of the deflection sensor is demonstrated in deflection and frequency measurements. True molecular-resolution FM-AFM images of a polydiacetylene single crystal taken in vacuum, air, and water are presented.
Background It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.
Objective: To study the effect of a new fermented milk product containing GABA (FMG) on the blood pressure (BP) of patients with mild hypertension. Design: A randomized, placebo-controlled, single-blind trial. Setting: The study was carried out at the outpatient clinic of the Cardiovascular Disease Center, Tokyo Metropolitan Police Hospital, Japan. Subjects: The study population comprised 39 mildly hypertensive patients (16 women and 23 men) aged 28 -81 y (mean, 54.2 y). Interventions: The study consisted of a 12-week period of daily intake of FMG or placebo (weeks 1 -12) followed by 2 weeks of no intake (weeks 13 and 14). We measured the peripheral BP and heart rate of seated patients at weeks 0, 2, 4, 8, 12 and 14. Routine blood study and urinalysis were performed before and after the intake. Results: There was a significant decrease of BP within 2 or 4 weeks, and it remained decreased throughout the 12-week intake period. For the FMG recipients, the mean decrease after 12 weeks was 17.4 AE 4.3 mmHg in the systolic BP (SBP) and 7.2 AE 5.7 mmHg in the diastolic BP (DBP). Both of these values differed statistically from baseline levels (P < 0.01), and the SBP of the FMG group differed from the placebo group (P < 0.05). Heart rate, body weight, hematological and blood chemistry variables, and urinalysis results (glucosuria and proteinuria) did not vary both groups throughout the study. Conclusion: FMG may contribute to lowering BP in mildly hypertensive people.
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