This chapter introduces the exploration of aging complexities, beginning from biological perspectives to provide a foundational understanding. The narrative highlights the evolution of the concept of “successful aging.” Then, the question of why we age is discussed, examining the shifting research paradigm from a focus on treating disease to disease prevention. To answer this question, a better understanding of aging biology is needed. By introducing the concept of successful aging, Rowe and Kahn underlined that individuals can potentially preserve and enhance their health through lifestyle habits. Premature aging, monogenic mutations, Blue Zones, and hallmarks of aging are featured here, as well as SuperAgers—those aged 80 or older with the cognition of middle-aged individuals and brains aging at much slower-than-average rates. Results demonstrate that diet, lifestyle, and environment influence inflammaging more than aging. The limitations of transcriptomics in understanding cognition and aging are also underscored, as well as the usefulness of proteomics in uncovering pathways and biomarkers in AD. Additionally, organ-derived plasma protein signatures are associated with future onset of pathologies, the aging brain, and connections with periphery relevant to health and longevity.