Mice live longer if you add melatonin to their drinking water. Researchers at the Universidad de Granada in Spain discovered this when they did experiments with two strains of mice that age rapidly. The tryptophan analogue improves the functioning of the mitochondria in the cells, and ensures that despite the process of ageing they get sufficient amounts of the energy molecule ATP.
The Spaniards used SAMR1 and SAMP8 mice for their experiments. These mice age faster – SA stands for senescence accelerated – and that’s why researchers like them for studying ageing processes. The researchers gave the mice 10 mg melatonin per kg bodyweight in their drinking water for their whole life. Mice in the control group were given water that did not contain melatonin.
The mice in the control group aged faster, probably because the cells’ power pack, the mitochondria, starts to show defects. They are no longer able to neutralise harmful compounds that are produced when food components are converted into energy. The researchers noticed that the mitochondria membranes in the control group mice had more corroded fatty acids, known in the jargon as lipid hydroperoxides [LPO].
5v = 5 months of ordinary drinking water; 10v = 10 months of ordinary drinking water; 10m = ten months of melatonin.
The enzymes in the mitochondria worked better when supplemented with melatonin. The researchers had already shown this in similar experiments with other cell types, such as brain cells. The endogenous antioxidant systems in the mitochondria work better, and the mitochondria keep on producing larger amounts of the energy molecule ATP to a greater age.
The mice that got melatonin lived longer. The effect was particularly pronounced in the SAMP8 mice: the ones that got melatonin lived four months longer.
The figures below are based on survival tests with female mice. The effect is probably even bigger in male mice. Male organisms have more genetic defects than females, which is why they generally die earlier.
“These effects suggest that pharmacological intervention with melatonin might help to ameliorate age and age-related disorders”, the researchers conclude. If you’re wondering whether they work for the supplements industry, we can set your mind at rest. The research was funded by the Spanish government.
Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice.
We investigated whether chronic melatonin administration influences mitochondrial oxidative stress and life span in mice. Diaphragmatic mitochondria from female senescent prone (SAMP8) and senescent resistant (SAMR1) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxidation, glutathione and glutathione disulfide, and glutathione peroxidase and reductase activities. Mitochondrial function was assessed by measuring the activity of the respiratory chain complexes and the ATP content. The results suggest that the age-dependent mitochondrial oxidative damage in the diaphragm of SAMP8 mice was accompanied by a reduction in the electron transport chain complex activities and in ATP levels. Furthermore, melatonin administration between 1 and 10 months of age normalized the redox and the bioenergetic status of the mitochondria and increased the ATP levels. Melatonin also increased both half-life and longevity, mainly in SAMP8 group. These results suggest an age-related increase in mitochondria vulnerability to oxidation in SAM mice at 10 months of age that was counteracted by melatonin therapy. The effects of melatonin on mitochondrial physiology probably underline the ability of the indoleamine to increase maximal life span in these animals.
PMID: 18485648 [PubMed – indexed for MEDLINE]