Study On The Association Between Aging And Inflammation, Oxidative Stress And Dietary Patterns In People With Different Glucose Toleranc

Background:China is rapidly transforming into an aging society and houses the largest elderly population in the world.The problem of ageing will inevitably give rise to formidable healthcare and socio-economic challenges.Recent studies have focused on the association of inflammation,oxidative stress and ageing.Type 2 diabetes mellitus(T2DM)is a leading risk factor for ageing and high levels of inflammation and oxidative stress.However,the underlying mechanisms are not well understood.This study evaluated the relationship between leukocyte telomere length(LTL)and mitochondrial DNA copy number(mtDNAcn)in subjects with different glucose tolerance statuses,in order to elucidate the underlying mechanisms of accelerated ageing in subjects with abnormal glucose metabolism.In addition,we investigated whether the indicators of oxidative stress and inflammation were involved and identified mediators among them.Hemoglobin Alc(HbA1c)is not consistently correlated with aging disorders in recent studies.Identification of a novel marker of glycemia and ageing will be useful.Interindividual differences in hemoglobin glycation(the hemoglobin glycation index(HGI))is correlated with inflammation and metabolic diseases.Thus,we also illustrated links between HGI and aging biomarkers,and explored the potential role of inflammation and oxidative stress in the correlations.in an effort to provide a potential indicator of ageing.Diet patterns contribute to advanced glycation end products(AGEs)and therefore increase inflammation and oxidative stress,which might be effective strategies for improvement in ageing.This study sought to develop a Chinese empirical dietary inflammatory index(CEDII)that assesses Chinese diet quality based on its inflammatory potential and examine whether the index was associated with an accelerated aging process,in order to provide intervention strategies for mitigating the health burden in aging societies.This study will illustrate the correlation of inflammation,oxidative stress and ageing from perspectives of mechanism,monitoring and treatment strategies.Methods:This study was a community-based cross-sectional study that was conducted in the Nankou community of Changping.Beijing.Dietary intake was collected based on 24-h dietary recalls.Participants performed a standardized 75 g oral glucose tolerance test(OGTT).and the levels of plasma glucose(PG).insulin(INS)and C-peptide(C-P)were measured at fasting and at 30,60 and 120 minutes.LTL and mtDNAcn were determined by polymerase chain reaction assay.Tumor necrosis factor α(TNF α)and interleukin-6(IL-6).8-oxo-2’-deoxyguanosine(8-oxo-dG),superoxide dismutase(SOD)activities,and glutathione reductase(GR)were measured.Result:1.Interaction between telomeres and mitochondria in subjects with different glucose tolerance statuses,and the roles of inflammation and oxidative stress in the relationship.A total of 450 subjects were included and divided into two groups according to a 75g OGTT:the abnormal glucose metabolism(AGM,n=257)group and the normal glucose tolerance(NGT,n=193)group.LTL and mtDNAcn were both inversely related to TNFα,IL-6,and SOD activity.Interaction between glucose metabolism and telomere length on mtDNAcn was significant(S 1.14,95%CI(1.07,4.91)).In the AGM,LTL was correlated with mtDNAcn(r=0.214,p=0.001),but no correlation was found in the NGT.The association between LTL and mtDNAcn was weakened after adjusting for inflammatory factors in the AGM(p=0.087)according to linear regressions.Mediation analysis demonstrated that TNFa was a significant mediator in the telomeremitochondrial interactome in the AGM.2.Associations of HGI,ageing,inflammation and oxidative stressA total of 434 subjects were included.The HGI was calculated as the difference between the measured and predicted hemoglobin A1c(HbA1c).The population was categorized into tertiles of the HGI.Participants in the high HGI group reported a shorter LTL.higher levels of TNFα,SOD activities,and HbA1c.Correlation analyses demonstrated that HGI was correlated with LTL(r=-0.25,P<0.001)and TNFα(r=0.19,P<0.001)regardless of HbA1c levels.No relationship was found between HGI and mtDNAcn.HGI(β=-0.238,p=0.015)and TNFα(β=-0.020,P<0.001)were proved to be correlated with LTL independently,using multiple linear regression analysis.Ordinal logistic regression models showed that compared with subjects of the high HGI group,the possibility of a higher-level LTL was 5.29-fold in the low HGI group(OR 5.29,95%CI(2.45,11.41),P<0.001).2.41-fold in the moderate HGI group(OR 2.41,95%CI(1.35.4.30),P=0.003)after controlling for confounding variables.Mediation analyses indicated that TNFa accounted for 30.39%of the effects of the HGI on LTL.3.Associations of diet patterns,aging,inflammation and oxidative stress.A total of 388 subjects were enrolled.the Chinese Diet Balance Index(DBI)and its derivatives,as well as the empirical dietary inflammatory pattern(EDIP)based on the western diet,were calculated for assessing dietary quality in different aspects.Chinese empirical dietary inflammatory index(CEDII)was derived using reduced-rank regression(RRR)according to Chinese diet patterns.The population was categorized into tertiles of the CEDII.High CEDII group was characterized by high intakes of refined grains,red meat and eggs,and less intakes of fat.This pattern predicted higher levels of TNF α,IL-6,shorter LTL and less mtDNAcn,CEDII was positively related to TNF α(r=0.32,p<0.001),IL-6(r=0.14,p=0.012)and SOD activities(r=0.13,p=0.020),but negatively associated with LTL(-0.15,p=0.003)and mtDNAcn(r=0.18.p<0.001).Neither DBI nor EDIP was correlated with biomarkers of inflammation or ageing.High CEDII scores were associated with short LTL and decreased mtDNAcn using multivariate linear regression with adjustment for age,sex,HbAlc,lipid profiles,and daily energy intake.The stratified analysis demonstrated that the high CEDII group had an increased risk of short LTL in subjects with abnormal glucose,lipid and blood pressure.Conclusion:1.Inflammation and oxidative stress may play vital roles in telomere shortening and mitochondrial dysfunction.The article suggested for the first time that there was a significant positive correlation between LTL and mtDNAcn in the subjects with hyperglycemia,which might be a potential mechanism for accelerated aging of the AGM.The relationship was completely mediated by TNF α.2.HGI was negatively related to telomere attrition,independent of HbAlc,which indicated that HGI might be a predictor of ageing.TNFα acted as a mediator of the relationship between HGI and LTL.No correlation between HGI and mtDNAcn was found.3.We developed a Chinese empirical dietary inflammatory index(CEDII).Dietary pattern high in refined grains,red meat and eggs,and low in fat.was associated with higher proinflammatory potential.High CEDII scores were correlated with an increased risk of ageing.Compared with indexes related to DBI and EDIP,CEDII was much more effective to assess inflammation and ageing potential of diet patterns.This study was the first to report the abnormal interaction between telomeres and mitochondria in people with abnormal glucose tolerance,indicating a potential mechanism of accelerated aging.In this article,individual differences in hemoglobin glycation were originally demonstrated to be correlated with ageing as a new marker.It was the first time to establish a model for evaluating dietary inflammation of Chinese dietary patterns,which built a bridge between diet,inflammation and aging,and provided a new strategy for individualized management of ageing.