The role of the heterochronic microRNA let-7 in the progression of aging

Aging results in reduced tissue homeostasis and declined ability to replace damaged cells by new functional ones. In many tissues, homeostasis and repair are supported by tissue-specific stem cells that induce to generate differentiated cells in accordance with physiological requirements. Heterochronic genes, initially described in worms, specify the timing of fate decisions in each cell type and thus ensure a synchronized program of development throughout the animal. The heterochronic let-7 microRNA plays an important role in development by repressing cell fate regulators to promote stage progression. Recent studies reveal a new role of let-7 which occurs much later in life and regulates aging of several tissues, across species. In this article I review the current knowledge on the fate mechanisms of tissue stem cells during aging that are modulate by let-7, as well as its co-partners and its target genes. I also discuss the therapeutic potential of controlling heterochronic events as a possible treatment for aging-related disorders. Timing is a clear dimension of organisms' development that may be difficult to witness in aging stages that are not as defined as in embryonic development. Exploring the regulation of stem cell aging by let-7 may ultimately reveal novel timing mechanisms.