Telomeres and Epigenetics in Endocrinology

Background: Telomere is regarded as the fundamental aspect of cellular aging and copper is recognized as one of the most essential trace elements. The role of dietary copper intake in telomere length maintenance is seldom examined. This study aims to investigate if telomere length is to be associated with daily dietary copper intake.

Methods: We used epidemiological data from a large national population-based health and nutrition survey. Dietary intake was assessed during the 24–h period before the interview date when blood sample was collected. Telomere length was measured from blood leukocyte using PCR method. The relationship between telomere length and dietary copper intake was assessed using multivariable linear regression models. We also examined if obesity, measured by body mass index, could modify the observed association.

Results: There are 7,324 participants had both leukocyte telomere length measured and dietary copper intake assessed, around 48.0% of them were men. Telomere length was longer in women than that in men (1.05 ± 0.26 vs. 1.00 ± 0.26 T/S ratio), while dietary copper intake was less in women than that in men (1.12 ± 0.80 vs. 1.51 ± 1.61 mg). After controlling for age, sex, ethnicity, physical activity, current smoking status, hypertension, cardiovascular diseases, and body mass index in the multivariable linear regression models, one unit increase of log-transformed dietary copper intake was significantly associated with longer telomere length (β = 0.02, 95% confidence interval: 0.01, 0.04). We did not find a significant sex difference for this association.

Conclusions: Dietary copper intake was significantly associated telomere length.The role of copper in human health might be involved in biological aging process.

Background/objectives: The pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD) and type-2 diabetes (T2D), is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular aging. However, leukocyte telomere length (LTL), the cellular biological aging indicator, is elusively linked with obesity. Recent studies indicate that sterol 27-hydroxylase (CYP27A1) is an emerging antiatherogenic enzyme, that, by converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates cholesterol removal via high-density lipoprotein-cholesterol (HDL-C). We tested the hypothesis that obese subjects who carry at least three copies of CYP27A1 low-hydroxylation (LH) activity genome-wide-validated alleles (rs4674345A, rs1554622A, and rs4674338G) present premature aging, as reflected in shorter LTL and higher levels of CVD/T2D risk factors, including reduced HDL-C.

Subjects/methods: Obese subjects from SPHERE project {n = 1,457; overweight [body mass index (BMI) 25–30 kg/m²] 65.8% and severe-obese (BMI > 30 kg/m²) 34.2%} were characterized for the presence from 0 to 6 LH-CYP27A1 allele copy number. Univariate and multivariable sex–age–smoking-adjusted linear-regression models were performed to compare CVD/T2D risk factors and biological aging (LTL) in relation to the combined BMI-LH groups: overweight-LH: 0–2, overweight-LH: 3–6, severe-obese-LH: 0–2, and severe-obese-LH: 3–6.

Results: Higher LTL attrition was found in severe-obese than overweight individuals (p < 0.001). Multivariable model reveals that among severe-obese patients those with LH: 3–6 present higher LTL attrition than LH: 0–2 (p < 0.05). Univariate and multivariable models remarkably show that insulin resistance is higher both in overweight-LH: 3–6 vs overweight-LH: 0–2 (p < 0.001) and in severe-obese-LH: 3–6 vs severe-obese-LH: 0–2 (p < 0.0001), and HDL-C is lower in overweight-LH: 3–6 than overweight-LH: 0–2 (p < 0.05 and p < 001). Finally, most of the well-known (i.e., blood pressure, heart rate, waist to hip, triglycerides, and HDL-C) and novel CVD risk factors [i.e., inflammation markers (C-reactive protein, leukocytes, and chemoattractant protein-1), fibrinogen, and glucose homeostasis (i.e., insulin resistance, and glycated hemoglobin)] are substantially (p < 0.0001) altered in severe-obese-LH: 0–2 vs overweight-LH: 0–2, pointing to the fact that obesity leads to worsen the CVD/T2D risk factor profile.

Conclusion: Our study supports evidence that CYP27A1 genetic characterization identifies persons at higher risk to develop CVD and T2D, on which better converge preventive measures, and opens new perspectives on mechanisms that link obesity with aging-related disorders.