The article explores the evolving understanding of aging and rejuvenation, highlighting the role of the epigenome in this process. It discusses the discovery that DNA methylation (DNAm) at specific CpG sites can serve as a highly accurate biomarker of age, known as the Horvath clock. This biomarker has been used to define biological age, which is more relevant than chronological age in understanding aging. The article also reviews the concept of programmed aging, where aging is seen as a genetically programmed process, and the idea that aging is driven by an epigenetic clock. The authors propose a bimodular epigenome model, where Module A represents the DNAm clock component and Module B represents the remainder of the epigenome. They discuss the potential of epigenetic rejuvenation as a strategy to reverse or arrest aging by resetting the epigenetic clock. Initial evidence suggests that while the clock can be forced to tick backwards, it only partially rejuvenates the phenotype. The article also explores various methods of cell reprogramming, including the use of Yamanaka factors, to achieve rejuvenation. It highlights the challenges and limitations of these approaches, such as the risk of teratomas in vivo and the need for safe and effective strategies. Finally, the article concludes that while the field of gerontology has seen a shift from viewing aging as an irreversible process to recognizing it as a reversible epigenetic process, more research is needed to fully understand and manipulate the epigenome to achieve rejuvenation.The article explores the evolving understanding of aging and rejuvenation, highlighting the role of the epigenome in this process. It discusses the discovery that DNA methylation (DNAm) at specific CpG sites can serve as a highly accurate biomarker of age, known as the Horvath clock. This biomarker has been used to define biological age, which is more relevant than chronological age in understanding aging. The article also reviews the concept of programmed aging, where aging is seen as a genetically programmed process, and the idea that aging is driven by an epigenetic clock. The authors propose a bimodular epigenome model, where Module A represents the DNAm clock component and Module B represents the remainder of the epigenome. They discuss the potential of epigenetic rejuvenation as a strategy to reverse or arrest aging by resetting the epigenetic clock. Initial evidence suggests that while the clock can be forced to tick backwards, it only partially rejuvenates the phenotype. The article also explores various methods of cell reprogramming, including the use of Yamanaka factors, to achieve rejuvenation. It highlights the challenges and limitations of these approaches, such as the risk of teratomas in vivo and the need for safe and effective strategies. Finally, the article concludes that while the field of gerontology has seen a shift from viewing aging as an irreversible process to recognizing it as a reversible epigenetic process, more research is needed to fully understand and manipulate the epigenome to achieve rejuvenation.