It is argued that aging research is at a stage where it could benefit greatly from a more intense engagement with the perspectives emphasized by systems biology and complexity science. A more integrated, systematic approach is needed if we are ever to have a fully developed, fundamental understanding of aging, longevity, and their relationship to health. A broader, deeper, more quantitative, and predictive conceptual framework can lead to theoretical approaches and realistic models that can be quantitatively confronted with data and, perhaps more importantly, stimulate novel questions and novel experiments. Integral to this is the search for underlying causal multilevel mechanisms and principles that can be quantified and developed into a serious predictive theoretical framework, providing a point of departure for framing a more integrated research agenda.