<p>Over the past decades, numerous studies aimed to discover the fundamental cause of the aging process. Rather than a single root cause, multiple factors were identified, suggesting that aging manifests itself through a progressive degradation of different molecules, cells and in the end, entire systems, directly affecting an individual’s health. To address this rapidly growing challenge, various anti-aging strategies have been proposed, among which partial reprogramming has emerged as a promising approach capable of extending both lifespan and healthspan. In this review, we summarize the historical development of aging theories, the effects of established anti-aging strategies, and the evolution of partial reprogramming using Yamanaka factors. We also highlight recent advances in overcoming the efficacy and safety limitations of partial reprogramming, as well as the remaining challenges that must be addressed to fully realize its therapeutic potential.</p>