Circulating miR-146a in healthy aging and type 2 diabetes: Age- and gender-specific trajectories

Mech Ageing Dev. 2019 Jun:180:1-10. doi: 10.1016/j.mad.2019.03.001. Epub 2019 Mar 14.

Abstract

To evaluate the combined effect of age and glycemic state on circulating levels of the inflamma-miR-146a levels, 188 healthy subjects (CTR) aged 20-104 years and 144 type-2 diabetic patients (T2DM), aged 40-80 years, were analyzed. In CTR subjects, miR-146a levels showed a significant age-related decline. When a gender-stratified analysis was ran, the miR-146a age-related trajectory was confirmed only in men and a negative correlation with PAI-1, uric acid, and creatinine was also observed. In women, miR-146a circulating levels showed negative correlations with azotemia, uric acid, waist/hip ratio and ferritin. A significant miR-146a decline with aging was also observed in T2DM patients. Significant positive correlations were found between miR-146a in diabetic patients and total cholesterol, LDL-C, ApoA1, ApoB, and platelets, and negative correlations with serum iron and ferritin. Notably, miR-146a was significantly overexpressed in T2DM patients treated with metformin. MiR-146a levels were significantly lower in diabetic patients than in age-matched CTR and negatively correlated to both fasting glucose and HbA1c in males. Finally, age-related trajectories for circulating miR-146a levels showed an inverted U-shaped relationship; however, in T2DM patients the trajectory was significantly shifted towards lower levels. Our findings support the hypothesis that miR-146a could be a functional biomarker of healthy/unhealthy aging.

Keywords: Age-associated diseases; Glycated hemoglobin; Inflammation; Lipid profile; microRNA.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Cell-Free Nucleic Acids / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Ferritins / blood
  • Humans
  • Iron / blood
  • Lipids / blood
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Sex Characteristics*

Substances

  • Cell-Free Nucleic Acids
  • Lipids
  • MIRN146 microRNA, human
  • MicroRNAs
  • Ferritins
  • Iron