Coping with stress is essential for all organisms, and several stress responses have evolved to maintain homeostasis. Senescence and autophagy are two of the most critical stress responses as (1) they respond to various types of stress and (2) they are closely associated with numerous age-related diseases and aging. Our overarching research goals are (1) to systematically identify the components that make up their regulatory networks; (2) to mechanistically understand the cellular and molecular logic of these systems; and (3) to define the nature of their dysregulation in age-related diseases and aging. In other words, We wish to understand how senescence and autophagy operate, why they are built the way they are, and what the consequence of their dysregulation is. We employ genetics, molecular biology, biochemistry, genomics, and cell biology with new technologies developed in our lab [e.g., SIP (selective autophagy substrates identification platform), LysoIP-DEG (immunopurified lysosomes followed by density gradient ultracentrifugation)] to advance these goals. A better understanding of these complex stress responses will provide new insights into the fundamental question of why we age. In principle, it will help the development of new therapeutic strategies for aging and age-related diseases, enhancing human health.