Aging is the result of a complex polygenetic trait characterized by decreased regeneration capacity and increased vulnerability to external and internal perturbations. Consequently, the inevitable process critically influences longevity, health, and disease susceptibility, ultimately leading to age-related pathologies and death. Gaining insights into inherent properties of aging and identifying definitive biomarkers and/or signatures are prerequisites for a better understanding and for the design of therapeutics for a wide range of age-related diseases that would improve the quality of life of the elderlies. However, a comprehensive understanding of the molecular mechanisms underlying aging has been hampered by its complex nature. Although the process has been subjected to substantial data-driven analyses including genomics, transcriptomics, and proteomics in a systemic manner, aging’s complexity hampers proper analysis as well as interpretation of the resulting outputs. Therefore, we review recent consequences focused on stem cell aging and age-related diseases.