Aging and rejuvenation: a modular epigenome model This article explores the concept of aging as an epigenetic process, focusing on the role of the epigenetic clock in determining biological age. The epigenetic clock, based on DNA methylation patterns, has been shown to accurately predict biological age. Research suggests that epigenetic rejuvenation, which involves reversing the epigenetic clock, may help slow or reverse aging. The study proposes a bimodular epigenome model, where module A represents the epigenetic clock and module B represents the rest of the epigenome. Epigenetic rejuvenation could be a key strategy for arresting or reversing organismal aging. The article discusses the concept of aging as a programmed process, supported by evidence from various organisms, including plants and animals. It also explores the potential of cell reprogramming to rejuvenate cells, with studies showing that reprogramming somatic cells to induced pluripotent stem (iPS) cells can reset the epigenetic clock. However, in vivo application of this method can lead to teratomas, prompting the development of cyclic partial cell reprogramming, which allows for partial rejuvenation without the risk of teratomas. The study also examines the dual effects of Yamanaka genes depending on the delivery method, showing that continuous expression can be regenerative in some cell types but toxic in others. Additionally, non-reprogramming strategies, such as the use of growth hormone, metformin, and dehydroepiandrosterone, have shown potential in rejuvenating epigenetic age in humans and rats. The article concludes that epigenetic rejuvenation, through both reprogramming and non-reprogramming strategies, holds promise for understanding and reversing the aging process. The epigenetic clock is proposed as a key driver of aging, and the modular epigenome model provides a framework for understanding how different components of the epigenome contribute to aging and rejuvenation. The study highlights the importance of further research to fully understand the mechanisms of epigenetic aging and to develop safe and effective strategies for rejuvenation.Aging and rejuvenation: a modular epigenome model This article explores the concept of aging as an epigenetic process, focusing on the role of the epigenetic clock in determining biological age. The epigenetic clock, based on DNA methylation patterns, has been shown to accurately predict biological age. Research suggests that epigenetic rejuvenation, which involves reversing the epigenetic clock, may help slow or reverse aging. The study proposes a bimodular epigenome model, where module A represents the epigenetic clock and module B represents the rest of the epigenome. Epigenetic rejuvenation could be a key strategy for arresting or reversing organismal aging. The article discusses the concept of aging as a programmed process, supported by evidence from various organisms, including plants and animals. It also explores the potential of cell reprogramming to rejuvenate cells, with studies showing that reprogramming somatic cells to induced pluripotent stem (iPS) cells can reset the epigenetic clock. However, in vivo application of this method can lead to teratomas, prompting the development of cyclic partial cell reprogramming, which allows for partial rejuvenation without the risk of teratomas. The study also examines the dual effects of Yamanaka genes depending on the delivery method, showing that continuous expression can be regenerative in some cell types but toxic in others. Additionally, non-reprogramming strategies, such as the use of growth hormone, metformin, and dehydroepiandrosterone, have shown potential in rejuvenating epigenetic age in humans and rats. The article concludes that epigenetic rejuvenation, through both reprogramming and non-reprogramming strategies, holds promise for understanding and reversing the aging process. The epigenetic clock is proposed as a key driver of aging, and the modular epigenome model provides a framework for understanding how different components of the epigenome contribute to aging and rejuvenation. The study highlights the importance of further research to fully understand the mechanisms of epigenetic aging and to develop safe and effective strategies for rejuvenation.