Mitochondria and the autophagy-inflammation-cell death axis in organismal aging Mitochondria are essential for cellular energy production and play a critical role in aging and disease. As mitochondria age, they become inefficient and potentially toxic, leading to apoptosis or necrosis. Mitochondria also contribute to pro-inflammatory signaling. Autophagy, a process that removes damaged or dysfunctional mitochondria (mitophagy), helps counteract degeneration, dampen inflammation, and prevent cell loss. Deficiencies in autophagy or mitophagy can lead to degenerative diseases and aging-associated pathologies. The interplay between mitochondria, autophagy, and inflammation is crucial in aging. Mitochondria produce reactive oxygen species (ROS) as a byproduct of normal respiration, which can cause DNA damage and mitochondrial dysfunction. Mitochondrial dysfunction, excessive ROS, or both are driving forces in aging as they reduce cellular fitness and cause damage to other organelles. Mitochondria also mediate acute cell death, such as apoptosis and necrosis, through the release of proteins that trigger self-destructive enzymatic cascades. Autophagy is a critical process for cellular adaptation to stress, innate immune responses, and quality control. It can occur generally or specifically target damaged mitochondria (mitophagy). Autophagy helps maintain cellular homeostasis by removing damaged components and recycling nutrients. However, impaired autophagy can lead to the accumulation of damaged mitochondria, promoting inflammation and cell death. Inflammation is a critical response to tissue damage and infection, but chronic inflammation is a major cause of aging-related diseases. Autophagy and apoptotic cell death tend to dampen inflammation, whereas necrotic cell death can promote it. Mitochondria play a central role in the activation of inflammasomes, which are molecular platforms that activate caspase-1 and process inflammatory cytokines. Mitochondrial damage can trigger the release of ROS and pro-inflammatory signals, leading to inflammation and cell death. Mitochondrial membrane permeabilization (MOMP) can result in the release of mitochondrial proteins that cause apoptosis. The mitochondrial permeability transition (MPT) can also lead to rapid necrotic cell death. Mitophagy is a specific form of autophagy that targets damaged mitochondria. It is regulated by proteins such as PINK1 and Parkin, which recognize and mark damaged mitochondria for degradation. Mitophagy is essential for maintaining mitochondrial quality and preventing the accumulation of dysfunctional mitochondria. Autophagy can confer cytoprotection by removing damaged mitochondria and reducing the risk of cell death. It also helps in the clearance of apoptotic cells and reduces inflammatory responses. Autophagy is crucial for maintaining cellular homeostasis and preventing the accumulation of toxic proteins and damaged organelles. Autophagy declines with age, and the expression of key autophagy genes is reduced in aging individuals. Conditions that promoteMitochondria and the autophagy-inflammation-cell death axis in organismal aging Mitochondria are essential for cellular energy production and play a critical role in aging and disease. As mitochondria age, they become inefficient and potentially toxic, leading to apoptosis or necrosis. Mitochondria also contribute to pro-inflammatory signaling. Autophagy, a process that removes damaged or dysfunctional mitochondria (mitophagy), helps counteract degeneration, dampen inflammation, and prevent cell loss. Deficiencies in autophagy or mitophagy can lead to degenerative diseases and aging-associated pathologies. The interplay between mitochondria, autophagy, and inflammation is crucial in aging. Mitochondria produce reactive oxygen species (ROS) as a byproduct of normal respiration, which can cause DNA damage and mitochondrial dysfunction. Mitochondrial dysfunction, excessive ROS, or both are driving forces in aging as they reduce cellular fitness and cause damage to other organelles. Mitochondria also mediate acute cell death, such as apoptosis and necrosis, through the release of proteins that trigger self-destructive enzymatic cascades. Autophagy is a critical process for cellular adaptation to stress, innate immune responses, and quality control. It can occur generally or specifically target damaged mitochondria (mitophagy). Autophagy helps maintain cellular homeostasis by removing damaged components and recycling nutrients. However, impaired autophagy can lead to the accumulation of damaged mitochondria, promoting inflammation and cell death. Inflammation is a critical response to tissue damage and infection, but chronic inflammation is a major cause of aging-related diseases. Autophagy and apoptotic cell death tend to dampen inflammation, whereas necrotic cell death can promote it. Mitochondria play a central role in the activation of inflammasomes, which are molecular platforms that activate caspase-1 and process inflammatory cytokines. Mitochondrial damage can trigger the release of ROS and pro-inflammatory signals, leading to inflammation and cell death. Mitochondrial membrane permeabilization (MOMP) can result in the release of mitochondrial proteins that cause apoptosis. The mitochondrial permeability transition (MPT) can also lead to rapid necrotic cell death. Mitophagy is a specific form of autophagy that targets damaged mitochondria. It is regulated by proteins such as PINK1 and Parkin, which recognize and mark damaged mitochondria for degradation. Mitophagy is essential for maintaining mitochondrial quality and preventing the accumulation of dysfunctional mitochondria. Autophagy can confer cytoprotection by removing damaged mitochondria and reducing the risk of cell death. It also helps in the clearance of apoptotic cells and reduces inflammatory responses. Autophagy is crucial for maintaining cellular homeostasis and preventing the accumulation of toxic proteins and damaged organelles. Autophagy declines with age, and the expression of key autophagy genes is reduced in aging individuals. Conditions that promote