Abstract
Background Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging. However, epidemiological research on dietary iron intake and cellular aging markers is scarce. The aim of this study was to explore the relationship between dietary iron intake and cellular aging markers and to investigate whether tumor necrosis factor-α (TNFα) mediated this relationship. Methods We conducted a cross-sectional analysis with a total of 467 subjects. Detailed dietary data were obtained using 24 h food recalls. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using real-time PCR assay. The association between dietary iron intake and cellular aging markers and TNFα and superoxide dismutase (SOD) was analyzed by Pearson correlation analysis and regression models adjusted by covariates. Simple mediation models were generated to examine whether TNFα mediated the association between iron intake and cellular aging markers using PROCESS macro Version 3.3. Results The study population contained more women than men, but their basic demographic and metabolic characteristics did not differ. After adjusting for age, LTL was the same for men and women, while mtDNAcn was lower in men. Multiple linear regression adjusted for confounding factors found that iron intake was negatively associated with LTL only in women and negatively associated with mtDNAcn only in men. Moreover, iron intake was positively associated with TNFα in both women and men but positively associated with SOD only in men. Path modeling showed that TNFα significantly mediated the indirect detrimental effect of iron intake on LTL only in women; in men, mediation of the indirect effect of iron intake on mtDNAcn by TNFα did not reach significance. Conclusions The study found sex-specific negative associations between dietary iron intake and cellular aging markers in that iron intake had deleterious effects on LTL attrition in women and mtDNAcn in men; only the former was partly mediated by TNFα. Consequently, when dietary iron intake and iron supplementation is recommended, the effects of iron imbalance on genomic stability and cellular aging markers must be considered.
Highlights
Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging
Subjects that did not have cellular aging marker, tumor necrosis factor-α (TNFα), or superoxide dismutase (SOD) data were not included in the study, leaving a total of 467 individuals that were selected for the experiment (normal glucose tolerance (NGT; n = 187, including 129 women and 58 men), prediabetes (n = 146, including 91 women and 55 men), and diabetes mellitus (DM; n = 134, including 86 women and 48men)) (Figure 1)
The peripheral blood mitochondrial DNA copy number (mtDNAcn) was significantly lower in men, but the leukocyte telomere length (LTL) was not different between women and men
Summary
Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging. The association between dietary iron intake and cellular aging markers and TNFα and superoxide dismutase (SOD) was analyzed by Pearson correlation analysis and regression models adjusted by covariates. Multiple linear regression adjusted for confounding factors found that iron intake was negatively associated with LTL only in women and negatively associated with mtDNAcn only in men. The study found sex-specific negative associations between dietary iron intake and cellular aging markers in that iron intake had deleterious effects on LTL attrition in women and mtDNAcn in men; only the former was partly mediated by TNFα. As human cell telomeres shorten with age, peripheral blood leukocyte telomere length (LTL) has come to be considered a reliable marker of cellular aging and age-related diseases [2]. Our previous study found that various dietary ingredients can have different effects on telomere length [9]
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