A molecular "switch" capable of "turning off" cellular processes which protect against aging and metabolic diseases has been identified by a team from the Harvard School of Public Health (HSPH).
While more research is needed, the findings may open doors for new drug treatments to halt or slow development of metabolic diseases like type 2 diabetes or heart disease.
Scientists want to better understand why some people - often those who are older, overweight, or obese - develop metabolic syndrome, a condition characterized by a group of risk factors, including high blood glucose, high cholesterol, insulin resistance, fatty liver, and increased abdominal fat.
This condition increases the risk of heart disease, type 2 diabetes, and other diseases, including cancer.
Using genetically altered mouse models, senior author Chih-Hao Lee, first author Shannon Reilly, an HSPH graduate student, and their colleagues focused on the role of the protein SMRT (silencing mediator of retinoid and thyroid hormone receptors) in the aging process.
They found aged cells accumulate more SMRT and wanted to see if SMRT increases the damaging effects of oxidative stress on mitochondria, the cell component that converts food and oxygen into energy and powers metabolic activities.
Oxidative stress is a cellular process that damages DNA, protein, and other cell functions and can lead to age-related diseases such as type 2 diabetes, Alzheimer's, Parkinson's, and atherosclerosis.
In laboratory experiments, Reilly, Lee, and colleagues found that in older animals SMRT acts like a "switch," turning off the protective cellular activities of proteins known as peroxisome proliferator-activated receptors (PPARs).
PPARs help regulate genes that promote fat burning to maintain lipid (blood fat) balance and reduce oxidative stress. The researchers were able to reduce the negative effects of oxidative stress by giving antioxidants or drugs known to turn the protective activities of PPARs back on.
PPAR drugs have been used to increase insulin sensitivity and lower blood lipid levels.
"Our study shows PPARs might also be used to boost the body's ability to handle oxidative stress," Lee said.
The findings appear in the December 1, 2010 issue of Cell Metabolism.