Telomere length predicts all-cause mortality in patients with type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetic patients with diabetic nephropathy have increased mortality and morbidity compared with normoalbuminuric patients. Telomere length in proliferative cells is inversely related to the total number of cell divisions, and therefore to biological age. We aimed to evaluate differences in telomere length in patients with type 1 diabetes with or without diabetic nephropathy; we also evaluated the prognostic value of telomere length. METHODS: In a prospective follow-up study, 157 type 1 diabetic patients with diabetic nephropathy and a control group of 116 patients with type 1 diabetes and normoalbuminuria were followed for 11.1 years (range 0.2-12.9). Telomere length was measured from DNA samples extracted from white blood cells at baseline. RESULTS: The mean telomere length did not differ between patients with or without diabetic nephropathy, and was similar in men and women, but was inversely correlated with age and systolic blood pressure, p < 0.05. When dividing patients into tertiles after telomere length, 36 (37%) patients died in the tertile with the shortest telomere length, 24 (28%) died in the middle tertile, and 15 (17%) of patients in the tertile with the longest telomere length died, log rank test p = 0.017. After adjustment for traditional risk factors, telomere length was still predictive of all-cause mortality. CONCLUSIONS/INTERPRETATION: In patients with type 1 diabetes we found no differences in telomere length between patients with or without diabetic nephropathy. We also found that telomere length was associated with all-cause mortality; however, confirmative studies are needed to verify our findings.

Action of boron at the molecular level: effects on transcription and translation in an acellular system.

It has been shown that boric acid has well-defined biological effects such as stimulation of wound healing in vivo, release of growth factors and cytokines, and increase of the extracellular matrice turnover. We examined its action at the molecular level, using cell-free systems of transcription (isolated placenta nuclei) and translation (wheat germ extract). We found that 10 mM boric acid greatly increased RNA synthesis, measured by absorbance at 260 nm (x 6.4) or by [3H]-UTP uptake (x 11). Full-length functional mRNA was produced because proteins of 14-80 kDa were translated. Among these proteins, factors involved in angiogenesis and, subsequently, in wound healing (VEGF and TGFbeta) were identified by slot blot, whereas growth factors such as FGF1 and TNFalpha were not detected. These results demonstrate that boron may contribute to biological cell activities at both the transcription and translation levels. However, the mechanism of action is still not known.

Study of telomere length and different markers of oxidative stress in patients with Parkinson's disease.

BACKGROUND: Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. METHODS: 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. RESULTS: There was a trend for lower TL in PD patients: 6.06 ± 0.81 kb in PD versus 6.45 ± 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). CONCLUSIONS: In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.

Telomere length in vascular tissues from patients with atherosclerotic disease.

OBJECTIVES: The present study was aimed at evaluating telomere length in blood and in different vascular tissues with or without atheroma, in 3 groups of subjects: a group of atherosclerotic subjects who underwent surgery (Atherosclerosis-Surgery), a second group of subjects with asymptomatic atherosclerotic carotid plaques but who did not undergo cardiovascular surgery (Atherosclerosis-No surgery), and a third group of subjects without atherosclerotic disease (Controls). The main objective was to determine if there is in vivo regulation of telomere length in situ by atherosclerotic lesions. METHODS: A total of 84 subjects (mean age 69 ± 8 years) were studied. Blood and arterial tissue telomere lengths were determined by Southern blotting. Personal medical history (diabetes, hypertension, cardiovascular disease, dyslipidemia), family medical history, drug intake, and lifestyle were evaluated in the entire population through the use of a questionnaire. RESULTS AND CONCLUSION: Arterial segments which did not develop atherosclerosis such as the saphenous vein and internal mammary artery, had longer telomere length than aortic segments. On the other hand, telomere length was shorter in aortic tissues which presented atherosclerotic lesions compared to corresponding tissues without atherosclerotic lesions. These results also suggest tissue regulation of telomere size by local factors likely related to oxidative stress responses.