This article delves into how Twelver Shia Islam responds to technological challenges, particularly focusing on radical life extension (RLE) within the trans-humanism paradigm. While there is a consensus among religions regarding spiritual and mental enhancement, body enhancement, including RLE, poses ethical and theological questions. After a brief introduction to the concepts of human existence, life, and death, I explore Shia rational reasoning, delving into the notions of the ‘rational impossible’ and ‘normal impossible’ in the context of RLE. Additionally, I investigate the relationship between RLE and the belief in Mahdism, which centers around the idea that the last Imam, al-Mahdi, lives in occultation and will eventually reappear as the promised savior. I also seek to understand the legitimacy of using technology to achieve longevity from the perspective of Shia Islam. Additionally, in the final section of the study, I present the viewpoints of four prominent Shia Mujtahids, obtained through email correspondence and Istefta. This Q&A section reveals multifaceted perspectives within the Shia community regarding RLE. Notably, the traditional group, referring to the intra-religious teachings, adopts a more open approach to the RLE issue, challenging prevailing stereotypes. This research emphasizes that, from the perspective of Shia Islam, a very long life is neither deemed impossible nor irrational. However, ethical considerations and potential side effects must be carefully weighed when implementing RLE technologies. Researchers and scientists bear the responsibility of using technology fairly and ethically, and avoiding any actions that may worsen various kinds of inequalities. Continuous exploration and dialogue are essential to gain a comprehensive understanding of the topic from the perspective of Shia Islam, as theological interpretations may evolve with scientific progress.