MicroRNA-663 induction upon oxidative stress in cultured human fibroblasts depends on the chronological age of the donor

Abstract

MicroRNAs, regulators of messenger RNA translation, have been observed to influence many physiological processes, amongst them the process of aging. Higher levels of microRNA-663 (miR-663) have previously been observed in human dermal fibroblasts subject to both replicative and stress-induced senescence compared to early passage cells. Also, higher levels of miR-663 have been found in memory T-cells and in human fibroblasts derived from older donors compared to younger donors. In previous studies we observed that dermal fibroblasts from donors of different chronological and biological age respond differentially to oxidative stress measured by markers of cellular senescence and apoptosis. In the present study we set out to study the association between miR-663 levels and chronological and biological age. Therefore we tested in a total of 92 human dermal fibroblast strains whether the levels of miR-663 in non-stressed and stressed conditions (fibroblasts were treated with 0.6μM rotenone in stressed conditions) were different in young, middle aged and old donors and whether they were different in middle aged donors dependent on their biological age, as indicated by the propensity for familial longevity. In non-stressed conditions the level of miR-663 did not differ between donors of different age categories and was not dependent on biological age. Levels of miR-663 did not differ dependent on biological age in stressed conditions either. However, for different age categories the level of miR-663 in stressed conditions did differ: the level of miR-663 was higher at higher age categories. Also, the ratio of miR-663 induction upon stress was significantly higher in donors from older age categories. In conclusion, we present evidence for an association of miR-663 upon stress and chronological age.