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Figure 2. Summary of the main changes associated with aging in the last steps of miRNA biogenesis pathway: pre-miRNA processing and maturation. (1) Dicer expression is generally reduced in aged tissues and cells, whereas its expression is induced by caloric restriction and aerobic exercise. In mice, a phosphomimetic mutation in Dicer1 induces accelerated aging, and specific KO of Dicer in adipose tissue has important effects on metabolism, leading to insulin resistance and premature aging. (2) The role of Argonaute proteins in aging is not well-established, as ALG-1 and ALG-2 (two Argonaute proteins in C. Elegans) have contrary effects on the lifespan of nematodes, and AGO2 mutations in Drosophila cause a reduced lifespan. The figure was created using BioRender.