Calorie restriction has consistently lead scientists to molecular pathways that slow aging, improve health. However, the exact mechanism was never fully understood. The earlier calorie intake is reduced, the greater the effect. Researchers at the University of Gothenburg have now identified one of the enzymes that hold the key to the aging process.
By consuming fewer calories, aging can be slowed down and the development of age-related diseases such as cancer and type 2 diabetes can be delayed.
As obesity reaches epidemic rates in Western countries, rather than closing the 30-year gap between healthspan and lifespan, the gap is likely to grow. It's even possible lifespan may decrease as people develop preventable diseases such as atherosclerosis, type 2 diabetes and certain forms of cancer.
"We are able to show that caloric restriction slows down aging by preventing an enzyme, peroxiredoxin, from being inactivated. This enzyme is also extremely important in counteracting damage to our genetic material," says Mikael Molin of the Department of Cell and Molecular Biology.
By gradually reducing the intake of sugar and proteins, without reducing vitamins and minerals, researchers have previously shown that monkeys can live several years longer than expected. The method has also been tested on everything from fishes and rats to fungi, flies and yeasts with favourable results. Caloric restriction also has favourable effects on our health and delays the development of age-related diseases. Despite this, researchers in the field have found it difficult to explain exactly how caloric restriction produces these favourable effects.
Using yeast cells as a model, the research team at the University of Gothenburg has successfully identified one of the enzymes required. They are able to show that active peroxiredoxin 1, Prx1, an enzyme that breaks down harmful hydrogen peroxide in the cells, is required for caloric restriction to work effectively.
The results, which have been published in the journal Molecular Cell, show that Prx1 is damaged during aging and loses its activity. Caloric restriction counteracts this by increasing the production of another enzyme, Srx1, which repairs Prx1. Interestingly, the study also shows that aging can be delayed without caloric restriction by only increasing the quantity of Srx1 in the cell. Repair of the peroxiredoxin Prx1 consequently emerges as a key process in aging.
"Impaired Prx1 function leads to various types of genetic defects and cancer. Conversely, we can now speculate whether increased repair of Prx1 during aging can counteract, or at least delay, the development of cancer."
Peroxiredoxins have also been shown to be capable of preventing proteins from being damaged and aggregating, a process that has been linked to several age-related disorders affecting the nervous system, such as Alzheimer's and Parkinson's. The researchers are accordingly also considering whether stimulation of Prx1 can reduce and delay such disease processes.