Unlocking mitochondrial dysfunction-associated senescence (MiDAS) with NAD⁺ - A Boolean model of mitochondrial dynamics and cell cycle control.

ABSTRACT: The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress - a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively capture

SUBMITTER: Sizek H 

PROVIDER: S-EPMC11380032 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature