The article by Tony Wyss-Coray discusses the complex relationship between aging, neurodegeneration, and brain rejuvenation. It highlights that while systemic diseases are a significant burden on human health, the aging brain is increasingly recognized as a key factor in the development of neurodegenerative conditions such as Alzheimer's disease (AD). The article reviews the evidence that circulating factors can modulate aging and rejuvenate various organs, including the brain. It emphasizes the importance of understanding the role of immune cells and secreted communication factors in brain aging and neurodegeneration. The review also explores the potential of using circulatory factors to stall or reverse these processes. Additionally, it discusses the overlap between aging and neurodegeneration, noting that many old brains show characteristic changes linked to neurodegeneration, but it is unclear whether these changes are precursors to disease or simply byproducts of aging. The article further examines the causes of brain aging and neurodegeneration, including genetic and environmental factors, and the role of inflammation. Finally, it reviews the concept of brain rejuvenation through the use of young plasma or heterochronic parabiosis, which has shown promising results in reversing age-related cognitive deficits in mice. The article concludes by emphasizing the need for further research to understand the mechanisms underlying these processes and to develop therapeutic approaches to counteract age-related cellular abnormalities in the brain.The article by Tony Wyss-Coray discusses the complex relationship between aging, neurodegeneration, and brain rejuvenation. It highlights that while systemic diseases are a significant burden on human health, the aging brain is increasingly recognized as a key factor in the development of neurodegenerative conditions such as Alzheimer's disease (AD). The article reviews the evidence that circulating factors can modulate aging and rejuvenate various organs, including the brain. It emphasizes the importance of understanding the role of immune cells and secreted communication factors in brain aging and neurodegeneration. The review also explores the potential of using circulatory factors to stall or reverse these processes. Additionally, it discusses the overlap between aging and neurodegeneration, noting that many old brains show characteristic changes linked to neurodegeneration, but it is unclear whether these changes are precursors to disease or simply byproducts of aging. The article further examines the causes of brain aging and neurodegeneration, including genetic and environmental factors, and the role of inflammation. Finally, it reviews the concept of brain rejuvenation through the use of young plasma or heterochronic parabiosis, which has shown promising results in reversing age-related cognitive deficits in mice. The article concludes by emphasizing the need for further research to understand the mechanisms underlying these processes and to develop therapeutic approaches to counteract age-related cellular abnormalities in the brain.