Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study

TLDR

Insulin resistance and oxidative stress are linked to accelerated leukocyte telomere attrition and are implicated in aging and hypertension. The study examined how leukocyte telomere length relates to insulin resistance, oxidative stress, and hypertension. Leukocyte terminal restriction fragment length was measured in 327 Caucasian men (mean age 62.2) from the Framingham Heart Study Offspring cohort. Telomere length decreased with age, insulin resistance, and oxidative stress, and hypertensive men had shorter age‑adjusted telomeres, indicating that hypertension, insulin resistance, and oxidative stress are associated with telomere shortening, largely driven by insulin resistance.

Abstract

Summary 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 2α ( 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.