Age- and sex-dependent changes in levels of circulating brain-enriched microRNAs during normal aging

Aging is a major risk factor for many common and life-threatening pathologies. The development of reliable biomarkers of aging should lead to a better understanding of aging-associated processes and facilitate the development of therapeutic regimens that delay aging. Levels of 38 brain-enriched microRNAs (miRNA) circulating in plasma were measured by quantitative RT-PCR in two age groups: 26-35 and 56-65 years old. An miRNA-pair approach was used for data normalization and determination of effective miRNA biomarker ratios. Nineteen miRNAs, comprising miRNA pairs and pair combinations (classifiers) that effectively differentiated the age and sex (individual pairs: 74-95% and 68-95%, respectively; classifiers: up to 100% accuracy) groups, were selected for further analysis of plasma samples from 5 donor age groups: 26-35, 36-45, 46-55, 56-65 and 66-75 years old. Dynamic changes in the plasma concentrations of certain miRNAs occurred at different ages in females and males, with peaks in the 46-55-year-old and 56-65-year-old groups, respectively. This finding suggests that the changes in miRNA levels can reflect centrally regulated processes, including changes in hormone levels during menopause. Certain miRNAs and miRNA pairs correlated with age in the sex-stratified groups at different ages and should be investigated further as potentially promising biomarkers of brain aging.