Mitochondrial Aging and Age-Related Dysfunction of Mitochondria

Figure 2

Mechanisms by which caloric restriction may improve mitochondrial function, delay mitochondrial aging, and expend longevity. Caloric restriction (CR) triggers several pathways that may lead to increased longevity via stimulation of mitochondrial function. The first mechanism includes the induction of sirtuin-1 (SIRT1), a protein deacetylase that in turn activates peroxisome proliferator-activated receptor-γ coactivator-α (PGC-1α). PGC-1α is a transcription factor involved in the activation of genes whose products are involved in mitochondrial biogenesis and respiration. CR also inhibits mammalian target of rapamycin (mTOR) signaling associated with an increase in the activity of eukaryotic translation initiation factor 4E binding protein (4E-BP) that stimulates the translation of genes encoding mitochondrial respiratory components. In C. elegans, CR activates the nuclear factor-erythroid 2-related factor-2 (NRF2) that regulates expression of several antioxidant genes and therefore may lengthen C. elegans lifespan through the reduction of oxidative stress and improving mitochondrial respiration.