U.S. researchers identify genetic link in biology of aging

Researchers with Oregon State University (OSU) have identified a protein, Nrf2, that is behind the breakdown in genetic communication causing syndromes associated with aging.

Nrf2 helps regulate gene expression and the body's reaction to various types of stressors.

In their study published in Free Radical Biology and Medicine, OSU researchers describe Nrf2 as both a monitor and a messenger, as it is constantly on the lookout for problems with cells that may be caused by many metabolic insults of life -- oxidative stress, toxins, pollutants and other metabolic dysfunction.

When it finds a problem, Nrf2 goes back to the cellular nucleus and rings the alarm bell, where it can "turn on" up to 200 genes that are responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other actions. About half of Nrf2 is used up every 20 minutes as it performs life-protective functions.

Metabolic insults routinely increase with age, and if things were working properly, the amount of Nrf2 that goes back into the nucleus should also increase to help deal with those insults. However, the level of nuclear Nrf2 declines with age.

"The levels of Nrf2, and the functions associated with it, are routinely about 30-40 percent lower in older laboratory animals," said Kate Shay, director of the Healthy Aging Core Laboratory at OSU and co-author on the study. "We've been able to show for the first time what we believe is the cause."

The researchers point to the increasing levels of a micro-RNA known as miRNA-146a.

Micro-RNAs help play a major role in genetic signaling, controlling what genes are "expressed," or turned on and off to perform their function.

In humans, miRNA-146a can turn on the inflammation processes that help prevent infection and begin the healing process. But with aging, researchers have found that miRNA-146a expression does not shut down properly, and it can significantly reduce the levels of Nrf2.

This can cause part of the chronic, low-grade inflammation that is associated with the degenerative diseases that now kill most people in the developed world, including heart disease, cancer, diabetes and neurological disease. "The action of miRNA-146a in older people appears to turn from a good to a bad influence," Shay was quoted as saying in a OSU news release. "It may be causing our detoxification processes to decline just when we need them the most."

The researchers believe some of the things found to be healthy for individuals, in diet or lifestyle, may be so because they help to conserve the proper balance between the actions of miRNA-146a and Nrf2.

It is possible to reduce excessive levels of miRNA-146a with compounds that interfere with its function, according to the researchers. Endit