Demissie S, Levy D, Benjamin E J, Cupples L A, Gardner J P, Herbert A, Kimura M, Larson M G, Meigs J B, Keaney J F, Aviv A
Boston University School of Public Health, Department of Biostatistics, Boston, MA, USA.
Aging Cell. 2006 Aug;5(4):325-30. doi: 10.1111/j.1474-9726.2006.00224.x.
Insulin 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(2alpha) (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.
胰岛素抵抗和氧化应激与白细胞端粒损耗加速有关。二者也都与衰老生物学以及包括高血压在内的衰老相关疾病有关。我们探讨了以端粒限制片段(TRF)长度表示的白细胞端粒长度与胰岛素抵抗、氧化应激和高血压之间的关系。我们在弗雷明汉心脏研究后代队列中测量了327名平均年龄为62.2岁(范围40 - 89岁)的白人男性的白细胞TRF长度。TRF长度与年龄呈负相关(r = -0.41,P < 0.0001),且年龄校正后的TRF长度与胰岛素抵抗稳态模型评估(HOMA-IR)呈负相关(r = -0.16,P = 0.007)以及与尿8-表前列腺素F2α(r = -0.16,P = 0.005)——全身氧化应激指标呈负相关。与血压正常的同龄人相比,高血压患者的年龄校正后TRF长度更短(高血压患者 = 5.93 +/- 0.042 kb,血压正常者 = 6.07 +/- 0.040 kb,P = 0.025)。总体而言,这些观察结果表明,高血压、胰岛素抵抗增加和氧化应激与白细胞端粒长度缩短有关,且高血压患者白细胞端粒长度缩短很大程度上归因于胰岛素抵抗。