<span style="mso-no-proof: yes;">The Toxicity of RNA Polymerase Inhibitors Opens the Door to New Drug Generation<span style="font-size: 10.0pt; mso-ansi-font-size: 18.0pt; font-family: 'Times New Roman',serif; mso-ascii-font-family: 'Palatino Linotype'; mso-hansi-font-family: 'Palatino Linotype'; font-weight: normal; mso-ansi-font-weight: bold;"> Modulating Longevity

There are many RNA polymerase inhibitors, such as rifampicin, which acts as an antituberculosis agent, and relatively new antiviral drugs, such as sofosbuvir. These drugs have a safe profile and strong efficacy in treating tuberculosis and hepatitis C infections. Studies have shown that high doses of these compounds promote cell longevity (prolonging life span) in humans. It is hypothesized that these drugs also affect human RNA polymerases at high doses. We predicted that such inhibition inhibits the RNA transcription machinery, which is considered a pacemaker of the biological clock. It is important to shift research to human RNA polymerase modulators to develop new versions of drugs treating diseases such as neurodegenerative disorders. Although there is no data about the crystal structure of the human RNA polymerase, the mammalian and even the bacterial structures look conserved. It is important to raise concerns about cancer risk from potential new drugs targeting RNA polymerase. However, adding adjuvant therapy, such as vascular endothelial growth factor inhibitors, to RNA polymerase inhibitors can be a wise strategy at the end of the tunnel. The speed of RNA polymerase elongation modulates longevity. Aging affects the transcription machinery, and transcription activity affects longevity, creating a loop.