Mitochondria and the autophagy-inflammation-cell death axis in organismal aging.

Alterations of mitochondrial functions are linked to multiple degenerative or acute diseases. As mitochondria age in our cells, they become progressively inefficient and potentially toxic, and acute damage can trigger the permeabilization of mitochondrial membranes to initiate apoptosis or necrosis. Moreover, mitochondria have an important role in pro-inflammatory signaling. Autophagic turnover of cellular constituents, be it general or specific for mitochondria (mitophagy), eliminates dysfunctional or damaged mitochondria, thus counteracting degeneration, dampening inflammation, and preventing unwarranted cell loss. Decreased expression of genes that regulate autophagy or mitophagy can cause degenerative diseases in which deficient quality control results in inflammation and the death of cell populations. Thus, a combination of mitochondrial dysfunction and insufficient autophagy may contribute to multiple aging-associated pathologies.

线粒体功能的改变与多种退行性或急性疾病有关。随着线粒体在我们细胞中老化，它们的效率逐渐降低且可能具有毒性，急性损伤会引发线粒体膜的通透性改变，从而启动细胞凋亡或坏死。此外，线粒体在促炎信号传导中具有重要作用。细胞成分的自噬转换，无论是一般性的还是针对线粒体的特异性自噬（线粒体自噬），都会清除功能失调或受损的线粒体，从而对抗退化、抑制炎症并防止不必要的细胞损失。调节自噬或线粒体自噬的基因表达降低会导致退行性疾病，在这些疾病中，质量控制缺陷会导致炎症和细胞群死亡。因此，线粒体功能障碍和自噬不足的共同作用可能导致多种与衰老相关的疾病。