Mitochondrial theory of ageing

During ATP production electrons can escape the mitochondrion and react with water, producing reactive oxygen species, ROS for short.

ROS can damage macromolecules, including lipids, proteins and DNA, which is thought to facilitate the process of ageing.

Mitochondria are thought to be organelles that developed from endocytosed bacteria which learned to coexist inside ancient cells.

ROS are highly reactive, oxygen-containing chemical species, which include superoxide, hydrogen peroxide and hydroxyl radical.

In fact, their presence at low levels lead to increased life span, by activating transcription factors and metabolic pathways involved in longevity.

Stress is sensed by the nucleus, where chaperones and proteases are upregulated, which can correct folding or remove damaged proteins, respectively.

Acetyl-coenzyme A (Acetyl-CoA) enters the TCA cycle in the mitochondrial matrix, and is oxidized in the process of energy production.

[17] Almaida-Pagan and coworkers found that mitochondrial membrane lipid composition changes with age, when studying Turquoise killifish.

[26][27] Bioinformatics analysis showed that amino acid composition of mitochondrial proteins correlate with longevity (long-living species are depleted in cysteine and methionine), linking mitochondria to the process of ageing.

[28][29] By studying expression of certain genes in C. elegans,[30] Drosophila,[31] and mice [32] it was found that disruption of ETC complexes can extend life – linking mitochondrial function to the process of ageing.

Mice with reduced expression of the mitochondrial antioxidant, SOD2, accumulated oxidative damage and developed cancer, but did not age faster.

[34][35] The naked mole-rat, which lives 10-times longer than normal mice, has been shown to have higher levels of oxidative damage.