Figure 8.

Overview of the SA effects of miR-21-5p and miR-217 carried by SEN sEVs into CON cells. (a) Graphic representation of the SA loop involving miR-21-5p. The miR-21 locus is de-methylated in SEN cells; the resulting miR-21-5p over-expression can contribute to reduce DNMT1/SIRT1 expression in SEN cells. sEVs released from SEN cells are enriched in miR-21-5p; their delivery to CON cells modulates DNMT1/SIRT1 and impairs their replication rate. This vicious cycle may be critical in maintaining the epigenetic “senescence program” through the spread of pro-senescence signals to younger cells through an increased sEV release. (b) MiR-21-5p in sEVs purified from plasma of healthy young, elderly and centenarian individuals showed an inverse U-shaped age-related trend, suggesting that miR-21-5p loaded on sEVs could be a systemic biomarker of senescence and inflammaging.