The breakthrough raises hopes that it might one day be possible to develop an anti-ageing drug for humans.
However, UK scientists have warned that such developments are still a long way off.
Lead researcher Dr Bruce Ames, of the University of California at Berkeley, said the results were astonishing.
He said: "With the two supplements together, these old rats got up and did the Macarena.
"The brain looks better, they are full of energy - everything we looked at looks more like a young animal."
The animals' memories were also significantly improved.
The researchers estimate that the effect on the rats was the equivalent making a 75 to 80-year-old person act middle-aged.
Found in the body
The chemicals used in the experiment were acetyl-L-carnitine and alpha-lipoic acid, both of which are normally found in the body's cells.
The combination of the two chemicals has now been patented by the University of California.
A company set up to exploit the patent, Juvenon, is already conducting human clinical trials.
Three research papers on different animal studies of the chemicals have been published in the journal Proceedings of the National Academy of Sciences.
The studies probed the biochemical action of the supplements, compared the behaviour of old and young rats, and tested the memory of animals fed the compounds.
Cell power house
The researchers found that the two chemicals in combination have a positive impact on mini-organs within the body's cells called mitochondria.
Mitochondria generate energy within the cells, and research has suggested that their deterioration is an important cause of ageing.
The problem seems to be that the very process of creating energy generates molecules called free radicals, which have a deeply destructive effect on the way cells work.
The supplement combination was found to mop up the free radicals in mitochondria.
It also boosts the activity of an enzyme fundamental to the energy-creating process.
The research also showed that mitochondria in brain cells important to memory were less damaged by radicals in animals fed the supplements.
Important research
Caroline Bradley, of the charity Research into Ageing, told BBC News Online that the study was clearly important.
She said: "The big step forward is that they have found a way of getting anti-oxidant into the mitochondria itself.
"Getting past the mitochondrial membrane has been the main challenge."
She added that it was early days for the research but that it was the first step towards improving human health in later life.
However, Professor David Colquhoun, an expert in pharmacology at University College London, said "Before rushing out to the local health food shop, perhaps people should bear in mind that this treatment has not yet been shown to be effective in humans, and neither has it been shown to be safe.
"The fact that the substances are naturally occurring does not guarantee their safety when they are given in unnatural doses.
"Even on the rats that they tested, any effects on memory are relatively small, though results in the water maze test might be interpreted as meaning that old rats can see or swim or cope with stress better after treatment.
"There is also no real reason to think that the two compounds work better together that separately on these tests.
"This may be an interesting lead, but only time will tell if it really works."