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Figure 1. Summary of the main changes associated with aging in the first three steps of the miRNA biogenesis pathway. (1) pri-miRNA transcription: during aging, RNA Pol II, the enzyme that transcribes pri-miRNAs, has an increased elongation speed and stalling, leading to an increased incidence of transcription errors. During cellular senescence, several transcription factors such as p53 are recruited and drive the expression of senescence-associated pri-miRNAs. (2) pri-miRNA processing: some members of the microprocessor complex, mainly Drosha and DGCR8, show decreased expression and activity during aging, and its expression is enhanced by mTOR inhibition and caloric restriction. Microprocessor inactivation leads to premature senescence and proliferation defects. (3) pre-miRNA export: an increased export of miRNAs to the cytoplasm has been observed during DNA damage response, contrary to what happens in cancer cells, with a decreased export. Disrupted nucleocytoplasmic trafficking has been observed during cellular senescence. The figure was created using BioRender.