MicroRNA, the putative molecular control for mid-life decline.

In a society experiencing an accelerating increase in the middle- and old-age population, there is an urgent need to address age-dependent frailties by a paradigm shift, i.e. a new medical strategy to combat middle-age decline at the stage before incipient old-age problems develop into full-blown diseases. We suggest that a decline in cellular health status occurs at mid-life, and that this decline may involve a universal or system-specific programmatic shift of signaling control. This decline, although sub-clinical and asymptomatic, may precipitate increased risk of late-life diseases. The putative control for this mid-life cellular decline may be governed by a recently discovered group of molecular species, the microRNAs, small RNAs of approximately 22 nucleotide bases. In general microRNAs, while themselves not coding for any protein product, negatively regulate the expression of target genes by either degrading their message or inhibiting translation by binding to their 3'-untranslated region (UTR). Thus, possible derailment of these negative regulators for gene expression in mid-life may be the putative force inducing molecular frailty in individual cell signaling, and in time leading to tissue-wide dysfunction. A challenge for future research is then to identify these dysfunctional microRNAs, in order to develop advance diagnosis and therapy to combat mid-life decline, a preventive medicine approach to block, delay or reduce the risk of old-age diseases.