Fighting aging 

By Dawn Wiseman

Assistant Biology Professor Vladimir Titorenko is exploring the key to youth through experimenting with yeast.  Magnifying glass

Assistant Biology Professor Vladimir Titorenko is exploring the key to youth through experimenting with yeast.

Ponce de Leon, it seems, was looking in the wrong place for the Fountain of Youth. According to Vladimir Titorenko (Biology), if a source of agelessness exists, it will not be found in a Floridian stream but somewhere in the genetic code of yeast. (Sorry, Snowbirds.)

Titorenko is the Concordia University Research Chair (Tier 2) in Genomics, Cell Biology and Aging. As the name suggests, he and the students in his lab are teasing out the genetic mechanisms of what makes us grow old.

Their primary subject of study is brewer’s yeast, Saccharomyces cerevisiae. Believe it or not, the microorganism is a good model for aging in many other organisms including worms, spiders, flies, fish and mice.

“In fact, all the genes that regulate aging in these animals,” he said, “were initially identified in yeast, so there is a strong connection between yeast and higher forms of life.”

It is for this reason that one of Titorenko’s recent discoveries has garnered a lot of attention.

About 70 years ago, researchers on aging discovered that reducing calorie intake in mice by 30 to 40% increased the rodents’ life spans by 20 to 30%. The exciting part of the finding was not so much the improved life span, but the associated improvement in health span; the mice were not only living longer, but also experiencing later onset of age-related conditions such as diabetes, cancer and neurodegenerative disorders.

“Let’s face it,” said Titorenko, “people don’t just want to live longer, the goal is to live longer and be healthy.”

Since the initial discovery, the calorie reduction results have been reproduced reliably in a number of species including dogs and monkeys. Trials with human volunteers are ongoing in the U.S. and U.K. Still no one had managed to identify the mechanisms at work until now.

Working with yeast, Titorenko and his colleagues have identified a series of changes that occur within cells on a strict but nutritionally complete diet.

“Calorie restriction appears not only to reduce fat accumulation in cells, but also to promote fat burning,” he explained. The double whammy against fats significantly decreases the levels of free fatty acids and other toxic lipids that damage cells.

The key to this improvement appears to be initiating the calorie reduction while the yeast is still relatively young. (Mice only benefit from the diet if they start it before their skeletal development is complete.)

Reduction in lipid accumulation also helps yeast avoid cell necrosis – a rather Monty Pythonesque-end where cells literally explode because they contain too much material.

Provided the yeast survives to old age, the diet has even more impact. It extends the length of time in which mitochondria, the cell’s power plants, function optimally.

“This maintenance increases resistance to different stresses, and the ability of the cell to fight damage through repair,” said Titorenko.

For example, the dieting yeast demonstrate a measurable increase in production of the sugar trehalose. This sugar attaches to damaged proteins and prevents them from joining together in clumps. These clumps are a key culprit in degenerative diseases like Alzheimer’s.

“With the dietary changes we have doubled the expected life span of yeast.”
They have also discovered a novel group of molecules that act as a drug for expanding the life span of yeast.

“It’s become a convenient tool for manipulating aging in our experiments,” said Titorenko.

He is considering patenting the drug and approaching pharmaceutical companies for further research. For the moment, he is collaborating with researchers at McGill, Johns Hopkins (Baltimore) and the Ottawa Heart Institute to see if the drug has any impact on human cell cultures.

“If we see results here, there is the potential it will have an effect on human aging,” but Titorenko is still very cautious. The only identified anti-aging drug is resveratrol, a substance found in red wine (and many an email spam message).

“Resveratrol extends the life span of yeast, worms, flies and fish, but does not increase the longevity of mice fed a standard diet,” he said. He doesn’t want his drug to end up as fodder for anyone’s spam filter.


Concordia University