Melatonin modulates neuronal mitochondria function during normal ageing in mice

Mitochondrial dysfunction has been shown to be associated with normal ageing and may account for age-related vulnerability to disease. The increasing number of old people worldwide has created the need to find effective therapeutic agents to reduce the incidence of age-related disease. In the current report, we carried out an assessment of mitochondrial function in established young, middle-aged and old synaptosomal mitochondria bearing cybrids without or with melatonin treatment. The cybrids were generated by transferring isolated mitochondria from synaptosomes of brain cortical cells in mice to rho-zero mtDNA-less cells. In galactose media, a selective media that tests a cells ability to produce ATP through the electron transport chain and oxidative phosphorylation, 500µM melatonin (N-acetyl-5-methoxytryptamine) raised cell viability in young and middle-aged cybrids (P<0.05) and a concentration of 1mM raised cell viability in the old cybrids (P<0.05). The mitochondrial membrane potential (MMP) was lowered in the young cybrids (P<0.05) treated with melatonin, but it was raised in the middle-aged and old cybrids (P<0.05) with melatonin treatment. The levels of reactive oxygen species were significantly lower in the melatonin treated middle-aged and old cybrids compared with controls (P<0.05). Furthermore, ATP measurements showed no significant increase in the young cybrids (P>0.05), but increased significantly in the middle-aged and old cybrids (P<0.05) with melatonin treatment. Light and fluorescence microscopy showed observable structural damage and cell death in the middle-aged and old cybrids without melatonin treatment. The results suggest that melatonin may be a potent therapeutic intervention during age-related neuronal mitochondrial dysfunction.