Circulating microRNAs during human aging and longevity

Strategies to promote active aging and counteract the development of age-related diseases are among the most challenging researches in the framework of Horizon 2020, accordingly with the World Health Organization's declaration that "increased longevity without quality of life is an empty prize†�. The aim of this thesis is to investigate the role of blood circulating microRNAs (miRs) and their expression profile characterizing aging and longevity trajectories, and particularly to distinguish between healthy and unhealthy longevity. To this purpose two experimental designs were defined, the former applied the advanced technology of smallRNA-sequencing (Illumina platform) to screen circulating miRs in a small cohort of different aged people, the latter was based on selected miRs analyzed on a larger cohort. The protocol for sequencing analysis, including library preparation, was optimized and applied on 12 donors, i.e. 3 young healthy donors, 3 old healthy donors, 3 healthy centenarians and 3 unhealthy centenarians. Significant miRs identified by sequencing, i.e. miR-30a-5p, -766-3p, -598-3p, were measured on a larger cohort of 48 subjects. Aging-related miRs previously described, i.e. miR-133a-3p, -206, -16, were analyzed in the same cohort of 48 donors. Circulating miR-206 and miR-16 levels described significant trajectories of aging, while miR-598-3p and miR-133a-3p levels characterized longevity trajectories. All these miRs are involved in the PI3K-Akt signaling, a central pathway for aging process. Finally, blood circulating molecules able to distinguish between healthy and unhealthy were obtained by joining the identified miRs and hemato-biochemical parameters, opening the possibility for further studies on therapeutic approaches.