Posts tagged telomeres
Articles and news from the latest research reports.
Longer Telomeres Linked to Risk of Brain Cancer
New genomic research led by UC San Francisco scientists reveals that two common gene variants that lead to longer telomeres, the caps on chromosome ends thought by many scientists to confer health by protecting cells from aging, also significantly increase the risk of developing the deadly brain cancers known as gliomas.
The genetic variants, in two telomere-related genes known as TERT and TERC, are respectively carried by 51 percent and 72 percent of the general population. Because it is somewhat unusual for such risk-conferring variants to be carried by a majority of people, the researchers propose that in these carriers the overall cellular robustness afforded by longer telomeres trumps the increased risk of high-grade gliomas, which are invariably fatal but relatively rare cancers.
The research was published online in Nature Genetics on June 8, 2014.
“There are clearly high barriers to developing gliomas, perhaps because the brain has special protection,” said Margaret Wrensch, MPH, PhD, the Stanley D. Lewis and Virginia S. Lewis Endowed Chair in Brain Tumor Research at UCSF and senior author of the new study. “It’s not uncommon for people diagnosed with glioma to comment, ‘I’ve never been sick in my life.’”
In a possible example of this genetic balancing act between risks and benefits of telomere length, in one dataset employed in the current study—a massive genomic analysis of telomere length in nearly 40,000 individuals conducted at the University of Leicester in the United Kingdom—shorter telomeres were associated with a significantly increased risk of cardiovascular disease.
“Though longer telomeres might be good for you as a whole person, reducing many health risks and slowing aging, they might also cause some cells to live longer than they’re supposed to, which is one of the hallmarks of cancer,” said lead author Kyle M. Walsh, PhD, assistant professor of neurological surgery and a member of the Program in Cancer Genetics at UCSF’s Helen Diller Family Comprehensive Cancer Center.
In the first phase of the new study, researchers at UCSF and The Mayo Clinic College of Medicine analyzed genome-wide data from 1,644 glioma patients and 7,736 healthy control individuals, including some who took part in The Cancer Genome Atlas project sponsored by the National Cancer Institute and National Human Genome Research Institute. This work confirmed a link between TERT and gliomas that had been made in previous UCSF research, and also identified TERC as a glioma risk factor for the first time.
Since both genes have known roles in regulating the action of telomerase, the enzyme that maintains telomere length, the research team combed the University of Leicester data, and they found that the same TERT and TERC variants associated with glioma risk were also associated with greater telomere length.
UCSF’s Elizabeth Blackburn, PhD, shared the 2009 Nobel Prize in Physiology or Medicine for her pioneering work on telomeres and telomerase, an area of research she began in the mid-1970s. In the ensuing decades, untangling the relationships between telomere length and disease has proved to be complex.
In much research, longer telomeres have been considered a sign of health—for example, Blackburn and others have shown that individuals exposed to chronic stressful experiences have shortened telomeres. But because cancer cells promote their own longevity by maintaining telomere length, drug companies have searched for drugs to specifically target and block telomerase in tumors in the hopes that cancer cells will accumulate genetic damage and die.
Walsh said the relevance of the new research should extend beyond gliomas, since TERT variants have also been implicated in lung, prostate, testicular and breast cancers, and TERC variants in leukemia, colon cancer and multiple myeloma. Variants in both TERT and TERC have been found to increase risk of idiopathic pulmonary fibrosis, a progressive disease of the lungs.
In some of these cases, the disease-associated variants promote longer telomeres, and in others shorter telomeres, suggesting that “both longer and shorter telomere length may be pathogenic, depending on the disease under consideration,” the authors write.
Genes increase the stress of social disadvantage for some children
Genes amplify the stress of harsh environments for some children, and magnify the advantage of supportive environments for other children, according to a study that’s one of the first to document how genes interacting with social environments affect biomarkers of stress.
"Our findings suggest that an individual’s genetic architecture moderates the magnitude of the response to external stimuli—but it is the environment that determines the direction" says Colter Mitchell, lead author of the paper and a researcher at the University of Michigan Institute for Social Research (ISR).
The study, published today in the Proceedings of the National Academy of Sciences, uses telomere length as a marker of stress. Found at the ends of chromosomes, telomeres generally shorten with age, and when individuals are exposed to disease and chronic stress, including the stress of living in a disadvantaged environment.
For the study, Mitchell and colleagues used telomere samples from a group of 40 nine-year-old boys from two very different environments – one nurturing and the other harsh. Those in the nurturing environment came from stable families, with nurturing parenting, good maternal mental health, and positive socioeconomic conditions, while those in the harsh environment experienced high levels of poverty, harsh parenting, poor maternal mental health, and high family instability.
For those children with heightened sensitivity in the serotonergic and dopaminergic genetic pathways compared to other children, telomere length was shortest in a disadvantaged environment, and longest in a supportive environment.
Loneliness impacts DNA repair: The long and the short of telomeres
Telomeres are DNA-protein complexes that function as protective caps at the ends of chromosomes. Biologists and veterinarians at the Vetmeduni Vienna recently examined the telomere length of captive African grey parrots. They found that the telomere lengths of single parrots were shorter than those housed with a companion parrot, which supports the hypothesis that social stress can interfere with cellular aging and a particular type of DNA repair. It suggests that telomeres may provide a biomarker for assessing exposure to social stress. The findings have been published in the open access journal PLOS ONE.
In captivity, grey parrots are often kept in social isolation, which can have detrimental effects on their health and wellbeing. So far there have not been any studies on the effects of long term social isolation from conspecifics on cellular aging. Telomeres shorten with each cell division, and once a critical length is reached, cells are unable to divide further (a stage known as ‘replicative senescence’). Although cellular senescence is a useful mechanism to eliminate worn-out cells, it appears to contribute to aging and mortality. Several studies suggest that telomere shortening is accelerated by stress, but until now, no studies have examined the effects of social isolation on telomere shortening.
Using molecular genetics to assess exposure to stress
To test whether social isolation accelerates telomere shortening, Denise Aydinonat, a doctorate student at the Vetmeduni Vienna, conducted a study using DNA samples that she collected from African grey parrots during routine check-ups. African greys are highly social birds, but they are often reared and kept in isolation from other parrots (even though such conditions are illegal in Austria). She and her collaborators compared the telomere lengths of single birds versus pair-housed individuals with a broad range of ages (from 1 to 45 years). Not surprisingly, the telomere lengths of older birds were shorter compared to younger birds, regardless of their housing. However, the important finding of the study was that single-housed birds had shorter telomeres than pair-housed individuals of the same age group.
Reading signs of stress by erosion of DNA
“Studies on humans suggest that people who have experienced high levels of social stress and deprivation have shorter telomeres,” says Dustin Penn from the Konrad Lorenz Institute of Ethology at the Vetmeduni Vienna. “But this study is the first to examine the effects of social isolation on telomere length in any species.” Penn and his team previously conducted experiments on mice, which were the first to show that exposure to crowding stress causes telomere shortening. He points out that this new finding suggests that both extremes of social conditions affect telomere attrition. However, he also cautions “further ‘longitudinal’ studies, in which changes in telomeres of the same individuals over time, are needed to investigate the consequences of stress on telomere shortening and the subsequent effects on health and longevity.”
Scientists discover hormone released after exercise can ‘predict’ biological age
Scientists from Aston University have discovered a potential molecular link between Irisin, a recently identified hormone released from muscle after bouts of exercise, and the ageing process.
Irisin, which is naturally present in humans, is capable of reprograming the body’s fat cells to burn energy instead of storing it. This increases the metabolic rate and is thought to have potential anti-obesity effects which in turn could help with conditions such as type-2 diabetes.
The research team led by Dr James Brown have proven a significant link exists between Irisin levels in the blood and a biological marker of ageing called telomere length. Telomeres are small regions found at the end of chromosomes that shorten as cells within the body replicate. Short telomere length has been linked to many age-related diseases including cancer, heart disease and Alzheimer’s disease.
Using a population of healthy, non-obese individuals, the team has shown those individuals who had higher levels of Irisin were found to have longer telomeres. The finding provides a potential molecular link between keeping active and healthy ageing with those having higher Irisin levels more ‘biological young’ than those with lower levels of the hormone.
Dr James Brown from Aston’s Research Centre for Healthy Ageing, said; “Exercise is known to have wide ranging benefits, from cardiovascular protection to weight loss. Recent research has suggested that exercise can protect people from both physical and mental decline with ageing. Our latest findings now provide a potential molecular link between keeping active and a healthy ageing process.”
The Aston Research Centre for Healthy Ageing takes a multidisciplinary approach to successful ageing by asking how technological, therapeutic and psychosocial strategies can be employed to understand and arrest age-related decline and degeneration.
Racism May Accelerate Aging in African American Men
A new University of Maryland-led study reveals that racism may impact aging at the cellular level. Researchers found signs of accelerated aging in African American men who reported high levels of racial discrimination and who had internalized anti-Black attitudes. Findings from the study, which is the first to link racism-related factors and biological aging, are published in the American Journal of Preventive Medicine.
Racial disparities in health are well-documented, with African Americans having shorter life expectancy, and a greater likelihood of suffering from aging-related illnesses at younger ages compared to whites. Accelerated aging at the biological level may be one mechanism linking racism and disease risk.
“We examined a biomarker of systemic aging, known as leukocyte telomere length,” explained Dr. David H. Chae, assistant professor of epidemiology at UMD’s School of Public Health and the study’s lead investigator. Shorter telomere length is associated with increased risk of premature death and chronic disease such as diabetes, dementia, stroke and heart disease. “We found that the African American men who experienced greater racial discrimination and who displayed a stronger bias against their own racial group had the shortest telomeres of those studied,” Chae explained.
Telomeres are repetitive sequences of DNA capping the ends of chromosomes, which shorten progressively over time – at a rate of approximately 50-100 base pairs annually. Telomere length is variable, shortening more rapidly under conditions of high psychosocial and physiological stress. “Telomere length may be a better indicator of biological age, which can give us insight into variations in the cumulative ‘wear and tear’ of the organism net of chronological age,” said Chae. Among African American men with stronger anti-black attitudes, investigators found that average telomere length was 140 base pairs shorter in those reporting high vs. low levels of racial discrimination; this difference may equate to 1.4 to 2.8 years chronologically.
Participants in the study were 92 African American men between 30-50 years of age. Investigators asked them about their experiences of discrimination in different domains, including work and housing, as well as in getting service at stores or restaurants, from the police, and in other public settings. They also measured racial bias using the Black-White Implicit Association Test. This test gauges unconscious attitudes and beliefs about race groups that people may be unaware of or unwilling to report.
Even after adjusting for participants’ chronological age, socioeconomic factors, and health-related characteristics, investigators found that the combination of high racial discrimination and anti-black bias was associated with shorter telomeres. On the other hand, the data revealed that racial discrimination had little relationship with telomere length among those holding pro-black attitudes. “African American men who have more positive views of their racial group may be buffered from the negative impact of racial discrimination,” explained Chae. “In contrast, those who have internalized an anti-black bias may be less able to cope with racist experiences, which may result in greater stress and shorter telomeres.”
The findings from this study are timely in light of regular media reports of racism facing African American men. “Stop-and-frisk policies, and other forms of criminal profiling such as ‘driving or shopping while black’ are inherently stressful and have a real impact on the health of African Americans,” said Chae. Researchers found that racial discrimination by police was most commonly reported by participants in the study, followed by discrimination in employment. In addition, African American men are more routinely treated with less courtesy or respect, and experience other daily hassles related to racism.
Chae indicated the need for additional research to replicate findings, including larger studies that follow participants over time. “Despite the limitations of our study, we contribute to a growing body of research showing that social toxins disproportionately impacting African American men are harmful to health,” Chae explained. “Our findings suggest that racism literally makes people old.”
(Image: Shutterstock)
Depression Linked to Telomere Enzyme, Aging, Chronic Disease
The first symptoms of major depression may be behavioral, but the common mental illness is based in biology — and not limited to the brain.
In recent years, some studies have linked major, long-term depression with life-threatening chronic disease and with earlier death, even after lifestyle risk factors have been taken into account.
Now a research team led by Owen Wolkowitz, MD, professor of psychiatry at UC San Francisco, has found that within cells of the immune system, activity of an enzyme called telomerase is greater, on average, in untreated individuals with major depression. The preliminary findings from his latest, ongoing study was reported Wednesday at the annual meeting of the American Psychiatric Association in San Francisco.
Telomerase is an enzyme that lengthens protective end caps on the chromosomes’ DNA, called telomeres. Shortened telomeres have been associated with earlier death and with chronic diseases in population studies.
The heightened telomerase activity in untreated major depression might represent the body’s attempt to fight back against the progression of disease, in order to prevent biological damage in long-depressed individuals, Wolkowitz said.
The researchers made another discovery that may suggest a protective role for telomerase. Using magnetic resonance imaging (MRI), they found that, in untreated, depressed study participants, the size of the hippocampus, a brain structure that is critical for learning and memory, was associated with the amount of telomerase activity measured in the white blood cells. Such an association at a single point in time cannot be used to conclude that there is a cause-and-effect relationship with telomerase helping to protect the hippocampus, but it is plausible, Wolkowitz said.
Telomerase Activity and Antidepressants
Remarkably, the researchers also found that the enzyme’s activity went up when some patients began taking an antidepressant. In fact, depressed participants with lower telomerase activity at baseline — as well as those in whom enzyme activity increased the most with treatment — were the most likely to become less depressed with treatment.
“Our results are consistent with the beneficial effect of telomerase when it is boosted in animal studies, where it has been associated with the growth of new nerve cells in the hippocampus and with antidepressant-like effects, evidenced by increased exploratory behavior,” Wolkowitz said. He cautions that his new findings are preliminary due to the small size of the study and must be confirmed through further research.
The researchers also measured telomere length in the same immune cells. Only very chronically depressed individuals showed telomere shortening, Wolkowitz said.
“The longer people had been depressed, the shorter their telomeres were,” he said. “Shortened telomere length has been previously demonstrated in major depression in most, but not all, studies that have examined it. The duration of depression may be a critical factor.”
Ongoing Study
The 20 depressed participants enrolled in the study had been untreated for at least six weeks and had an average lifetime duration of depression of about 13 years. After baseline evaluation and laboratory measures, 16 of the depressed participants were treated with sertraline, a member of the most popular class of antidepressants, the serotonin-selective-reuptake-inhibitors (SSRIs), and then evaluated again after eight weeks. There were 20 healthy participants who served as controls.
The ongoing study still is accepting depressed participants who are not now taking antidepressants.
Wolkowitz’s team also studies chronic inflammation and the biochemical phenomenon of oxidative stress, which he said have often been reported in major depression. Wolkowitz is exploring the hypothesis that inflammation and oxidative stress play a role in telomere shortening and accelerated aging in depression.
“New insights into the mechanisms of these processes may well lead to new treatments — both pharmacological and behavioral — that will be distinctly different from the current generation of drugs prescribed to treat depression,” he said. “Additional studies might lead to simple blood tests that can measure accelerated immune-cell aging.”
(Source: ucsf.edu)
Test that can predict death - with a terrifying degree of accuracy
A blood test to determine how fast someone is ageing has been shown to work on a population of wild birds, the first time the ageing test has been used successfully on animals living outside a laboratory setting.
The test measures the average length of tiny structures on the tips of chromosomes called telomeres which are known to get shorter each time a cell divides during an organism’s lifetime.
Telomeres are believed to act like internal clocks by providing a more accurate estimate of a person’s true biological age rather than their actual chronological age.
This has led some experts to suggest that telomere tests could be used to estimate not only how fast someone is ageing, but possibly how long they have left to live if they die of natural causes.
Telomere tests have been widely used on experimental animals and at least one company is offering a £400 blood test in the UK for people interested in seeing how fast they are ageing based on their average telomere length.
Now scientists have performed telomere tests on an isolated population of songbirds living on an island in the Seychelles and found that the test does indeed accurately predict an animal’s likely lifespan.
“We saw that telomere length is a better indicator of life expectancy than chronological age. So by measuring telomere length we have a way of estimating the biological age of an individual – how much of its life it has used up,” said David Richardson of the University of East Anglia.
Wandering Minds Associated With Aging Cells
Scientific studies have suggested that a wandering mind indicates unhappiness, whereas a mind that is present in the moment indicates well-being. Now a preliminary UCSF study suggests a possible link between mind wandering and aging, by looking at a biological measure of longevity.
In the study, telomere length, an emerging biomarker for cellular and general bodily aging, was assessed in association with the tendency to be present in the moment versus the tendency to mind wander, in research on 239 healthy, midlife women ranging in age from 50 to 65 years.
Being present in the moment was defined as an inclination to be focused on current tasks, while mind wandering was defined as the inclination to have thoughts about things other than the present or being elsewhere.
According to the findings, published online on Nov. 15 in the new Association for Psychological Science journal Clinical Psychological Science, those who reported more mind wandering had shorter telomeres, while those who reported more presence in the moment, or having a greater focus and engagement with their current activities, had longer telomeres, even after adjusting for current stress.
Omega-3 Supplements May Slow A Biological Effect of Aging
Taking enough omega-3 fatty acid supplements to change the balance of oils in the diet could slow a key biological process linked to aging, new research suggests.
The study showed that most overweight but healthy middle-aged and older adults who took omega-3 supplements for four months altered a ratio of their fatty acid consumption in a way that helped preserve tiny segments of DNA in their white blood cells.
These segments, called telomeres, are known to shorten over time in many types of cells as a consequence of aging. In the study, lengthening of telomeres in immune system cells was more prevalent in people who substantially improved the ratio of omega-3s to other fatty acids in their diet.
Omega-3 supplementation also reduced oxidative stress, caused by excessive free radicals in the blood, by about 15 percent compared to effects seen in the placebo group.
“The telomere finding is provocative in that it suggests the possibility that a nutritional supplement might actually make a difference in aging,” said Jan Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State and lead author of the study.