C-peptide is a predictor of telomere shortening: A five-year longitudinal study

Abstract

AimRelative telomere length (RTL) predicts the development of many age-related diseases. Yet, few studies have evaluated their longitudinal effect on RTL. We investigated longitudinally the association between cardiometabolic risk factors and RTL.MethodsThis was a longitudinal study with a 5-year follow-up period, based on data collected in 2014 and 2019. Of 478 participants in 2014, 198 consented to be followed-up in 2019. The associations between RTL and risk factors were analyzed using t-test, ANOVA or simple linear regression as applicable.ResultsRTL was significantly shortened after 5 years (P<0.001). Older age (P=0.018) and gender (P=0.05) were significantly associated with shorter RTL at follow-up. Higher baseline C-peptide correlated with shorter RTL (P=0.04) and shortening of RTL (P=0.03) after 5 years. Multivariate linear regression including both age and gender revealed a significant trend for C-peptide and change in RTL after 5 years (P=0.04). Interestingly, there was a trend of shorter RTL at follow-up with diabetes, though the findings were not statistically significant.ConclusionsHigher C-peptide level contributes to telomere shortening over time, suggesting that metabolic dysregulation may play a role in early aging. Further understanding of this relationship and addressing high C-peptide levels can be important to prevent premature aging.

Insulin and aging – a disappointing relationship

“…Cross-sectional studies suggest that that insulin resistance is associated with increased telomere shortening in some groups but not in others ( 108 – 112 ). A positive association was also noted in the follow-up of cohorts ( 113 – 115 ) with one exception ( 116 ). These observational studies also found an association between telomere attrition and other parameters such as adiposity, hypertension or circulating sirtuin-1 concentrations.…”

Advances in the study of the correlation between insulin resistance and infertility

“…Telomere length is critical for maintaining the divisional capacity of oocytes, and once telomeres are depleted, the cell will immediately initiate the apoptotic program and progress toward apoptosis ( 54 ). One mechanism by which IR-induced hyperglycemic states may promote telomere shortening is through oxidative stress, which produces oxygen free radicals that affect telomere ends, which are enriched with guanine residues, the latter of which make them susceptible to oxidative stress ( 55 ). Oocytes are prone to chromosome segregation errors during meiosis, resulting in aneuploidy, and these factors include crossover problems when recombination occurs in meiotic M I, spindle assembly checkpoint (SAC) deletion, and so on, which may independently induce aneuploidy in oocytes, or they may be interrelated ( 56 ).…”