A team of Harvard School of Public Health (HSPH) scientists report finding a molecular "switch" that can "turn off" some cellular processes that are protective against aging and metabolic diseases.
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. The research findings appear in the December 1, 2010 issue of Cell Metabolism.
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, assistant professor of genetics and complex diseases at HSPH, 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.
The scientists knew that oxidative damage causes the body to age. What they did not know is why aged cells have more oxidative damage. "The significance of our study is that we show SMRT facilitates this process," Lee said. "In other words, the normal metabolic homeostasis is maintained, in part, by PPARs. SMRT acts as a metabolic switch to turn off PPAR activities when the cells age."
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.
"With what we have learned, we believe SMRT is one of the key players that causes age-dependent decline in mitochondrial function by blocking PPAR activity, and we've found a way to boost the body's ability to better handle metabolic and oxidative stress," Lee said. "This finding is significant since increased oxidative stress, coupled with reduced metabolic function, contributes to the aging process and the development of age-related metabolic diseases."
In collaboration with epidemiologists at HSPH, the team found genetic variations in the human SMRT gene that are associated with risk of type 2 diabetes. "Through this study we were able to validate that our findings in the animal model apply to human diseases," Lee said.
Support for the study was from the National Institutes of Health as well as from the American Diabetes Association and American Heart Association. Lee received a Career Incubator Fund from HSPH that also supported the work.
"Nuclear Receptor Corepressor SMRT Regulates Mitochondrial Oxidative Metabolism and Mediates Aging-Related Metabolic Deterioration," Shannon M. Reilly, Prerna Bhargava, Sihao Liu, Matthew R. Gangl, Cem Gorgun, Russell R. Nofsinger, Ronald M. Evans, Lu Qi, Frank Hu, Chih-Hao Lee. Cell Metabolism, December 2010.
Visit the HSPH website for the latest news, press releases and multimedia offerings.
Harvard School of Public Health (http://www.hsph.harvard.edu) is dedicated to advancing the public's health through learning, discovery, and communication. More than 400 faculty members are engaged in teaching and training the 1,000-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children's health to quality of care measurement; from health care management to international health and human rights. For more information on the school visit: http://www.hsph.harvard.eduHSPH on Twitter: http://twitter.com/HarvardHSPH
Marjorie Dwyer | EurekAlert!
Desert ants cannot be fooled
23.11.2017 | Max-Planck-Institut für chemische Ökologie
Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Earth Sciences
23.11.2017 | Physics and Astronomy
23.11.2017 | Power and Electrical Engineering