The article discusses the multifaceted mechanisms and risk factors contributing to systemic chronic inflammation (SCI), which is increasingly recognized as a significant contributor to global morbidity and mortality. SCI is characterized by low-grade, persistent inflammation that can lead to various diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative disorders. The authors highlight the importance of understanding the interplay between social, environmental, and lifestyle factors, such as infections, physical inactivity, poor diet, environmental toxicants, and psychological stress, in promoting SCI. They also emphasize the need for robust biomarkers and integrative approaches to study SCI, as well as the importance of early intervention to prevent and treat SCI-related diseases. The article concludes by calling for further research to better understand the role of SCI in disease risk, biological aging, and mortality, and to develop effective strategies for improving human health.The article discusses the multifaceted mechanisms and risk factors contributing to systemic chronic inflammation (SCI), which is increasingly recognized as a significant contributor to global morbidity and mortality. SCI is characterized by low-grade, persistent inflammation that can lead to various diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative disorders. The authors highlight the importance of understanding the interplay between social, environmental, and lifestyle factors, such as infections, physical inactivity, poor diet, environmental toxicants, and psychological stress, in promoting SCI. They also emphasize the need for robust biomarkers and integrative approaches to study SCI, as well as the importance of early intervention to prevent and treat SCI-related diseases. The article concludes by calling for further research to better understand the role of SCI in disease risk, biological aging, and mortality, and to develop effective strategies for improving human health.