(Press-News.org) In human cells, shortened telomeres, the protective caps at the ends of chromosomes, are both a sign of aging and contribute to it. Scientists at Emory University School of Medicine have found that the dietary supplement alpha lipoic acid (ALA) can stimulate telomerase, the enzyme that lengthens telomeres, with positive effects in a mouse model of atherosclerosis.
The discovery highlights a potential avenue for the treatment for chronic diseases.
The results were published Thursday, August 20 in Cell Reports.
"Alpha-lipoic acid has an essential role in mitochondria, the energy-generating elements of the cell," says senior author Wayne Alexander, MD, PhD, professor of medicine at Emory University School of Medicine. "It is widely available and has been called a 'natural antioxidant'. Yet ALA's effects in human clinical studies have been a mixed bag."
ALA appears to exert its effects against atherosclerosis by spurring the smooth muscle cells that surround blood vessels to make PGC1 (peroxisome proliferator-activated receptor gamma co-activator 1)-alpha. PGC1-alpha was already well known to scientists as controlling several aspects of how skeletal muscles respond to exercise. While the Emory researchers did not directly assess the effects of exercise in their experiments, their findings provide molecular clues to how exercise might slow the effects of aging or chronic disease in some cell types.
"The effects of chronic diseases such as atherosclerosis and diabetes on blood vessels can be traced back to telomere shortening," Alexander says. "This means that treatments that can restore healthy telomeres have great potential."
"What's new here is that we show that PGC1-alpha is regulating telomerase, and that has real beneficial effects on cellular stress in a mouse model of atherosclerosis," says Shiqin Xiong, PhD, instructor in the division of cardiology and first author of the paper.
Xiong and Alexander used a model of atherosclerosis where mice lacked the ApoE cholesterol processing gene and were fed a high-fat diet. In this model, mice also lacking PGC1-alpha have more advanced plaques in their blood vessels, but only in older animals, the authors show.
Consistent with the poorer state of their blood vessels, aortic cells from PGC1-alpha-disrupted mice had shorter telomeres and reduced telomerase activity. Having shortened telomeres led the smooth muscle cells to display more oxidative stress and damage to the rest of their DNA.
The authors show that introducing PGC1-alpha back into vascular smooth muscle cells lacking that gene with a gene-therapy adenovirus could restore telomerase activity and lengthen the cells' telomeres.
Telomerase is off in most healthy cell types and only becomes turned on when cells proliferate. Because telomerase is active in cancer cells and enables their continued growth, researchers have been concerned that stimulating telomerase in all cells might encourage cancer growth or have other adverse effects.
As a way to boost PGC1-alpha in cells more conveniently, Xiong and Alexander turned to alpha lipoic acid or ALA. ALA is a sulfur-containing fatty acid used to treat diabetic neuropathy in Germany, and has previously been shown to combat atherosclerosis in animal models.
Treating isolated smooth muscle cells with ALA for one day could both stimulate PGC1-alpha and telomerase, the authors found. ALA's effects on vascular smooth muscle cells could also be seen when it was injected into mice. Xiong and Alexander say they are now investigating the effects of ALA on other tissues in mice. They have not observed increased cancers in ALA-treated mice, but say more thorough investigation is needed to fully assess cancer risk.
"While ALA is present in many foods and its effects in animal models look promising, it may be problematic for clinical use because of its poor solubility, stability and bioavailability," Xiong says. "We are designing new ways to formulate and deliver ALA-related compounds to resolve these issues."
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Co-authors include assistant professor Lu Hilenski, PhD, Nikolay Patrushev, MD and Farshad Forouzandeh, MD, PhD.
(Boston)--Poor sleep may impact treatment and recovery in veterans with Post-Traumatic Stress Disorder (PTSD) and Traumatic Brain Injury (TBI). A review of extensive research on sleep in TBI and PTSD has found that sleep-focused interventions can improve treatment outcomes in veterans.
Led by researchers at Boston University School of Medicine (BUSM) and VA Boston Healthcare System, the review article currently appears online in the journal of Clinical Psychology Review.
Sleep difficulty is a primary symptom of both PTSD and TBI and has been found to affect the severity ...
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In a survey of more than 4,000 New Zealand residents, a nationally ...
Water pollution has been a historical and stubborn problem in the water resource management. Several water pollution accidents continually occurred all over the world, threatening the safety of industry, agriculture and drinking water for resident's life (see Figure 1). An innovative and efficient approach was identified to study the complicated mechanism of water pollution in alluvial rivers.
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Researchers at the University of Strathclyde are developing groundbreaking plasma based light amplifiers that could replace traditional high power laser amplifiers.
The research group at the Glasgow-based University are leading efforts to take advantage of plasma, the ubiquitous medium that makes up most of the universe, to make the significant scientific breakthrough.
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New research by European and African scientists, including a team from the University of York, warns of the risks posed by the increasing air pollution over the cities of West Africa - amid fears it could have an impact on human health, meteorology and regional climate.
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Millions more have their lives shortened by ill health due to the effects of chewing tobacco-based products, the study reveals.
Researchers say it is the first time the global impact of smokeless tobacco consumption on adults has been assessed.
The team, which included collaboration from the University of Edinburgh and Imperial College, London, says governments and public health bodies need to consider incorporating the regulation ...
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The East London Family (ELF) Study found that a mother's perception of effective general family functioning has a significant effect on limiting the intake of sugary foods and drinks by their three and four year old children. In contrast, less effective family functioning leads to high frequency intake of sugary foods and drinks by three and four year old children ...
While the benefits of cooperation in human society are clear, new research from The University of Nottingham suggests it also has a dark side - one that encourages corrupt behaviour.
"Collaborative settings, not just greed, can provide fertile ground for corruption, as typified by recent scandals in the football and banking worlds. But while much is known about individual immoral behaviour, little is known about the collaborative roots of corruption," explains lead author Dr Ori Weisel from the School of Economics at the University.
The study, The Collaborative Roots ...
ORANGE, Calif. - Researchers in Chapman University's Food Science Program have just published two separate studies on meat mislabeling in consumer commercial products. One study focused on identification of species found in ground meat products, and the other focused on game meat species labeling. Both studies examined products sold in the U.S. commercial market; and both study outcomes identified species mislabeling among the product samples.
In the study on identification of species found in ground meat products, 48 samples were analyzed and 10 were found to be mislabeled. ...
Los Angeles, CA (August 21, 2015) With the globalization of biomedical research and growing concerns about possible pandemics of diseases such as HIV, SARS, and Ebola, international data-sharing practices are of growing interest to the biomedical science community. But what are the advantages and disadvantages of sharing data in low and middle-income settings? What challenges stand in the way for researchers in countries such as India, Kenya, and Vietnam? A new special issue of SAGE's Journal of Empirical Research on Human Research Ethics (JERHRE) presents guidelines, protocols, ...
