The mysterious and inescapable process of aging often comes with chronic diseases like diabetes, heart disease and cancer.
Scientists at the University of New Mexico Comprehensive Cancer Center have discovered a new class of drugs that combats an important part of the aging process. Eric Prossnitz, PhD, led the UNM team that published its results in Science Signaling.
Prossnitz studies G protein-coupled estrogen receptor – or GPER – that helps determine how our cells respond to the hormone estrogen and to estrogen-like substances and plays a role in diseases like breast cancer and diabetes.
“GPER mediates many beneficial functions in physiology,” says Prossnitz, professor in the Department of Internal Medicine at the UNM School of Medicine and the Victor and Ruby Hansen Surface Endowed Professor in Cancer Chemical Biology.
In one study, he found that making GPER more active in mice placed on a high-fat diet reduced the development of atherosclerosis – narrowing and hardening of the blood vessels. But another study’s results with old mice surprised him, leading his team to discover new mechanisms of aging – and a new way to defeat them.
Prossnitz’s team studied mice that lacked GPER in all their cells as they aged, tracking them over the normal mouse life span of about two years. They expected these mice to show increased levels of age-related disease in their hearts and blood vessels. Instead, compared with normal aged mice, the GPER-lacking mice had healthier hearts and blood vessels.
The team then conducted a series of experiments to learn why. They discovered an altered balance between certain signaling molecules in the smooth muscle cells of blood vessels and the heart.
One of those signaling molecules, superoxide, is a type of reactive oxygen species. These molecules react strongly with nearby cellular proteins, impeding their activity. Over time, the cell’s proteins and other components degrade enough to prevent normal cell functions.
“Almost every disease of aging is influenced by reactive oxygen species,” Prossnitz says. The blood vessels of people (and mice) with chronic diseases like diabetes, heart disease and cancer show signs of accelerated aging.
The team tested whether their patented GPER-blocking drug would improve smooth muscle cell function. They found it changed how the blood vessels’ smooth muscle cells expressed their genes. One of the genes affected produces a protein called NOX1, which produces superoxide.
By blocking GPER, the team’s drug also blocked NOX1, reducing the amount of superoxide the cell produced and slowing cellular aging. “It may not be a cure for aging,” Prossnitz says of the drug, “but it may greatly delay the aging process.”
Prossnitz hopes this approach will one day lead to a treatment for the diseases of aging. That day is still a long way off— the drug must first be developed for human use and then thoroughly tested. But Prossnitz and his team hope to help people live longer and better with chronic conditions.