Figure 1. Mechanistic view of the hallmarks of aging.

Schematic overview of the molecular, cellular, and phenotypic processes of aging, grouped into early, intermediate, and late events, emphasizing the sequential and temporal character of the process of aging. Any type of stress/disturbance can induce epigenetic changes, transcriptional noise, nuclear and mitochondrial DNA damage, loss of cell membrane integrity, and oxidative stress, among other molecular disturbances. Intermediate events of aging encompass cellular responses to stress-induced molecular alterations and include activation of inflammation, proteostasis, autophagy, senescence, establishing energy homeostasis, and rewiring of cellular metabolism. If not resolved, molecular and cellular alterations due to repeated stress throughout the life of the individual trigger late events of aging, which manifest as aging phenotypes. Late events of aging result in progressive deterioration of organ function and include stem cell exhaustion, organ dysfunction, loss of tissue integrity, immune system dysfunction, for example, chronic low levels of inflammation, and alterations in tissue–tissue interactions and cell–cell communication. Molecular, cellular, and phenotypic processes of aging are interconnected, and progression in one process induces the progression of all other processes.