Centenarians exhibit extreme longevity and a remarkable compression of morbidity. They have a unique capacity to maintain homeostatic mechanisms. Since small non-coding RNAs (including microRNAs) are implicated in the regulation of gene expression, we hypothesised that longevity of centenarians may reflect alterations in small non-coding RNA expression. We report the first comparison of microRNAs expression profiles in mononuclear cells from centenarians, octogenarians and young individuals resident near Valencia, Spain. Principal Component Analysis of the expression of 15,644 mature microRNAs and, 2,334 snoRNAs and scaRNAs in centenarians revealed a significant overlap with profiles in young individuals but not with octogenarians and a significant up-regulation of 7 small non-coding RNAs in centenarians compared to young persons and notably 102 small non-coding RNAs when compared with octogenarians. We suggest that the small non-coding RNAs signature in centenarians may provide insights into the underlying molecular mechanisms endowing centenarians with extreme longevity.

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