Pistachio consumption modulates DNA oxidation and genes related to telomere maintenance: a crossover randomized clinical trial

Abstract

Background: Telomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D), increasing the probability of β cell senescence and leading to reduced cell mass and decreased insulin secretion. Nutrition and lifestyle are known factors modulating the aging process and insulin resistance/secretion, determining the risk of T2D.

Objectives: The aim of this study was to evaluate the effects of pistachio intake on telomere length and other cellular aging-related parameters of glucose and insulin metabolism.

Methods: Forty-nine prediabetic subjects were included in a randomized crossover clinical trial. Subjects consumed a pistachio-supplemented diet (PD, 50 E% [energy percentage] carbohydrates and 33 E% fat, including 57 g pistachios/d) and an isocaloric control diet (CD, 55 E% carbohydrates and 30 E% fat) for 4 mo each, separated by a 2-wk washout period. DNA oxidation was evaluated by DNA damage (via 8-hydroxydeoxyguanosine). Leucocyte telomere length and gene expression related to either oxidation, telomere maintenance or glucose, and insulin metabolism were analyzed by multiplexed quantitative reverse transcriptase-polymerase chain reaction after the dietary intervention.

Results: Compared with the CD, the PD reduced oxidative damage to DNA (mean: -3.5%; 95% CI: -8.07%, 1.05%; P = 0.009). Gene expression of 2 telomere-related genes (TERT and WRAP53) was significantly upregulated (164% and 53%) after the PD compared with the CD (P = 0.043 and P = 0.001, respectively). Interestingly, changes in TERT expression were negatively correlated to changes in fasting plasma glucose concentrations and in the homeostatic model assessment of insulin resistance.

Conclusions: Chronic pistachio consumption reduces oxidative damage to DNA and increases the gene expression of some telomere-associated genes. Lessening oxidative damage to DNA and telomerase expression through diet may represent an intriguing way to promote healthspan in humans, reversing certain deleterious metabolic consequences of prediabetes. This study was registered at clinicaltrials.gov as NCT01441921.

FIGURE 1

Percentage changes in plasma 8-OHdG levels in the course of the interventions. Results are means (95% CI) of 2 replicate samples for each point. *Significant compared with pistachio diet (P < 0.05). n = 49, both periods are considered. 8-OHdg, 8-hydroxydeoxyguanosine.

FIGURE 2

Multivariable-adjusted differences (95% CI) in changes in TL z score after the intervention period, adjusted by age and baseline TL. There was no significant difference between the changes. n = 49, limited to the first intervention period due to carryover effect. TL, telomere length.

FIGURE 3

Expression relative to the baseline of the genes across intervention diets. Data are given as means (95% CI). Values equal to 1 mean the same expression at baseline and at the end of a particular period, whereas values >1 mean upregulation throughout the intervention period and <1 mean downregulation. *Significant differences in changes between dietary interventions (P < 0.05). n = 49, both periods are considered.

FIGURE 4

Boxplots of the associations between TERT regulation (i.e., upregulation or downregulation) and baseline-adjusted changes in biochemical parameters related to glucose metabolism, insulin resistance, and metabolic derangements associated with T2D. Gene expression was categorized as upregulated/downregulated if there was an up/down 1.5-fold change in the levels within the PD diet and CD diet. Changes in expression are shown as the ratio between final and baseline values. *P < 0.05, between TERT groups (i.e., TERT Up and TERT Down). Dots represent outliers from the data in each intervention period for each variable analyzed. n = 49, both periods are considered.

FIGURE 5

Pearson correlations between TERT and WRAP53 and expression of different miRNAs related to glucose and insulin metabolism. Results represent the coefficient of correlation based on a black-to-white scale. *P < 0.05, **P < 0.01, ***P < 0.001. n = 49, both periods and intervention groups are considered simultaneously. miR, microRNA.