The structure of long telomeres in chromosomes of the Iberian shrew

It is shown that the size, localization, and structure of telomeres in the Iberian shrew (Sorex granarius) are not characteristic of mammals. In this species, long telomeres of an average size of 213 kb are localized on the short arms of all 32 acrocentrics; ribosomal blocks and active nucleolus-organizing regions (NORs) were also discovered there. At the remaining chromosome ends the average size of telomeres is 3.8 kb. However, in a closely related species, Sorex araneus, all telomeres have size similar to that of human telomeres, i.e., 6.8–15.2 kb. Despite the fact that some long telomeres contain ribosomal repeats in addition to telomeric ones, the long telomeres have preserved asymmetry of G- and C-rich strands as in functional telomeres. It is probable that long telomeres were formed in meiosis at the stage of chromosome bouquet as a result of global reorganization of the chromosome ends. The provoking factors for such reorganization might be the fission of several metacentrics and the necessity of telomerization of the resulting acrocentrics.     

ESCRTing in cereals: still a long way to go

The multivesicular body(MVB) sorting pathway provides a mechanism for the delivery of cargo destined for degradation to the vacuole or lysosome. The endosomal sorting complex required for transport(ESCRT) is essential for the MVB sorting pathway by driving the cargo sorting to its destination. Many efforts in plant research have identified the ESCRT machinery and functionally characterised the first plant ESCRT proteins. However, most studies have been performed in the model plant Arabidopsis thaliana that is genetically and physiologically different to crops. Cereal crops are important for animal feed and human nutrition and have further been utilized as promising candidates for recombinant protein production. In this review, I summarize the role of plant ESCRT components in cereals that are involved in efficient adaptation to environmental stress and grain development. A special focus is on barley(Hordeum vulgare L.) ESCRT proteins, where recent studies show their quantitative mapping during grain development, e.g. associating HvSNF7.1 with protein trafficking to protein bodies(PBs) in starchy endosperm. Thus, it is indispensable to identify the molecular key-players within the endomembrane system including ESCRT proteins to optimize and possibly enhance tolerance to environmental stress, grain yield and recombinant protein production in cereal grains.     

DNA vaccine against malaria: a long way to go

Vaccination is the attempt to mimic certain aspects of an infection for the purpose of causing an immune response that will protect the individual from that infection. Malaria, a disease responsible for immense human suffering, is caused by infection with Plasmodium spp. parasites, which have a very complex life cycle--antigenically unique stages infect different tissues of the body. It is a parasitic disease for which no successful vaccine has been developed so far, despite considerable efforts to develop a subunit vaccine that offers protective immunity. Due to the spread of drug-resistant malaria, efforts to develop an effective vaccine have become increasingly critical. DNA vaccination provides a stable and long-lived source of protein vaccine capable of inducing both antibody- and cell-mediated immune responses to a wide variety of antigens. Injected DNA enters the cells of the host and makes the protein, which triggers the immune response. According to present needs, the flexibility of DNA vaccine technology permits the combination of multiple antigens from both the preerythrocytic and erythrocytic stages of malaria parasite. DNA vaccines with genes coding for different antigenic parts of malaria proteins have been created and presently some of these are undergoing field trials. The results from these trials will help to determine the likelihood of success of this technology in humans. This review presents an update of the studies carried out in malaria using DNA vaccine approach, the challenges, and the future prospects.     

Embryonic axes: the long and short of it in the mouse

Contrary to conventional wisdom, recent studies indicate that, during mouse development, the embryo's anterior-posterior axis shifts from the shorter transverse axis to the orthogonal longer one as the shape of the pre-gastrula-stage embryo is remodelled.     

Wildlife consumption and conservation awareness in China: a long way to go

An attitudinal survey on wildlife consumption and conservation awareness was conducted in Beijing, Shanghai, Guangzhou, Kunming and Nanning of China recently. Comparison with the results from a similar survey we did in 2004, after 8 years, the proportion of respondents who had consumed wildlife was dropped slightly from 31.3 % down to 29.6 %. It showed that the rates of wildlife consumed as food and as ingredients for traditional medicines in Guangzhou and Nanning ranked in the top. The consumptions in these two cities were mostly driven by utilitarian motivation, and mainly for food. Meanwhile, the rate of consumers taking wildlife as food was declining significantly in Beijing after 8 years. The results also showed that 52.7 % agreed that wildlife should not be consumed, which was significantly increased comparison with the survey result of 42.7 % in 2004. In addition, respondents agreed that wildlife could be used significantly decline from 42.8 to 34.8 %. It’s indicated that wildlife conservation awareness was raised in China in the past years. We also founded that consumers with higher income and higher educational background were having higher wildlife consumption rate. It suggested that to strengthen the law enforcement and to promote the public awareness were keys to reduce wildlife consumption in China.     

Telomere elongation (Tel), a new mutation in Drosophila melanogaster that produces long telomeres.

In most eukaryotes telomeres are extended by telomerase. Drosophila melanogaster, however, lacks telomerase, and telomere-specific non-LTR retrotransposons, HeT-A and TART, transpose specifically to chromosome ends. A Drosophila strain, Gaiano, that has long telomeres has been identified. We extracted the major Gaiano chromosomes into an Oregon-R genetic background and examined the resulting stocks after 60 generations. In situ hybridization using HeT-A and TART sequences showed that, in stocks carrying either the X or the second chromosome from Gaiano, only the Gaiano-derived chromosomes display long telomeres. However, in stocks carrying the Gaiano third chromosome, all telomeres are substantially elongated, indicating that the Gaiano chromosome 3 carries a factor that increases HeT-A and TART addition to the telomeres. We show that this factor, termed Telomere elongation (Tel), is dominant and localizes as a single unit to 69 on the genetic map. The long telomeres tend to associate with each other in both polytene and mitotic cells. These associations depend on telomere length rather than the presence of Tel. Associations between metaphase chromosomes are resolved during anaphase, suggesting that they are mediated by either proteinaceous links or DNA hydrogen bonding, rather than covalent DNA-DNA bonds.     

Women and telomeres

Last year''s Nobel Prizes for Carol Greider and Elizabeth Blackburn should be encouraging for all female scientists with childrenCarol Greider, a molecular biologist at Johns Hopkins University (Baltimore, MD, USA), recalled that when she received a phone call from the Nobel Foundation early in October last year, she was staring down a large pile of laundry. The caller informed her that she had won the 2009 Nobel Prize in Physiology or Medicine along with Elizabeth Blackburn, her mentor and co-discoverer of the enzyme telomerase, and Jack Szostak. The Prize was not only the ultimate reward for her own achievements, but it also highlighted a research field in biology that, unlike most others, is renowned for attracting a significant number of women.Indeed, the 2009 awards stood out in particular, as five women received Nobel prizes. In addition to the Prize for Greider and Blackburn, Ada E. Yonath received one in chemistry, Elinor Ostrom became the first female Prize-winner in economics, and Herta Müller won for literature (Fig 1).Open in a separate windowFigure 1The 2009 Nobel Laureates assembled for a photo during their visit to the Nobel Foundation on 12 December 2009. Back row, left to right: Nobel Laureates in Chemistry Ada E. Yonath and Venkatraman Ramakrishnan, Nobel Laureates in Physiology or Medicine Jack W. Szostak and Carol W. Greider, Nobel Laureate in Chemistry Thomas A. Steitz, Nobel Laureate in Physiology or Medicine Elizabeth H. Blackburn, and Nobel Laureate in Physics George E. Smith. Front row, left to right: Nobel Laureate in Physics Willard S. Boyle, Nobel Laureate in Economic Sciences Elinor Ostrom, Nobel Laureate in Literature Herta Müller, and Nobel Laureate in Economic Sciences Oliver E. Williamson. © The Nobel Foundation 2009. Photo: Orasis.Greider, the daughter of scientists, has overcome many obstacles during her career. She had dyslexia that placed her in remedial classes; “I thought I was stupid,” she told The New York Times (Dreifus, 2009). Yet, by far the biggest challenge she has tackled is being a woman with children in a man''s world. When she attended a press conference at Johns Hopkins to announce the Prize, she brought her children Gwendolyn and Charles with her (Fig 2). “How many men have won the Nobel in the last few years, and they have kids the same age as mine, and their kids aren''t in the picture? That''s a big difference, right? And that makes a statement,” she said.The Prize […] highlighted a research field in biology that, unlike most others, is renowned for attracting a significant number of womenOpen in a separate windowFigure 2Mother, scientist and Nobel Prize-winner: Carol Greider is greeted by her lab and her children. © Johns Hopkins Medicine 2009. Photo: Keith Weller.Marie Curie (1867–1934), the Polish–French physicist and chemist, was the first woman to win the Prize in 1903 for physics, together with her husband Pierre, and again for chemistry in 1911—the only woman to twice achieve such recognition. Curie''s daughter Irène Joliot-Curie (1897–1956), a French chemist, also won the Prize with her husband Frédéric in 1935. Since Curie''s 1911 prize, 347 Nobel Prizes in Physiology or Medicine and Chemistry (the fields in which biologists are recognized) have been awarded, but only 14—just 4%—have gone to women, with 9 of these awarded since 1979. That is a far cry from women holding up half the sky.Yet, despite the dominance of men in biology and the other natural sciences, telomere research has a reputation as a field dominated by women. Daniela Rhodes, a structural biologist and senior scientist at the MRC Laboratory of Molecular Biology (Cambridge, UK) recalls joining the field in 1993. “When I went to my first meeting, my world changed because I was used to being one of the few female speakers,” she said. “Most of the speakers there were female.” She estimated that 80% of the speakers at meetings at Cold Spring Harbour Laboratory in those early days were women, while the ratio in the audience was more balanced.Since Curie''s 1911 prize, 347 Nobel Prizes in Physiology or Medicine and Chemistry […] have been awarded, but only 14—just 4%—have gone to women…“There''s nothing particularly interesting about telomeres to women,” Rhodes explained. “[The] field covers some people like me who do structural biology, to cell biology, to people interested in cancers […] It could be any other field in biology. I think it''s [a result of] having women start it and [including] other women.” Greider comes to a similar conclusion: “I really see it as a founder effect. It started with Joe Gall [who originally recruited Blackburn to work in his lab].”Gall, a cell biologist, […] welcomed women to his lab at a time when the overall situation for women in science was “reasonably glum”…Gall, a cell biologist, earned a reputation for being gender neutral while working at Yale University in the 1950s and 1960s; he welcomed women to his lab at a time when the overall situation for women in science was “reasonably glum,” as he put it. “It wasn''t that women were not accepted into PhD programs. It''s just that the opportunities for them afterwards were pretty slim,” he explained.“Very early on he was very supportive to a number of women who went on and then had their own labs and […] many of those women [went] out in the world [to] train other women,” Greider commented. “A whole tree that then grows up that in the end there are many more women in that particular field simply because of that historical event.Thomas Cech, who won the Nobel Prize for Chemistry in 1989 and who worked in Gall''s lab with Blackburn, agreed: “In biochemistry and metabolism, we talk about positive feedback loops. This was a positive feedback loop. Joe Gall''s lab at Yale was an environment that was free of bias against women, and it was scientifically supportive.”Gall, now 81 and working at the Carnegie Institution of Washington (Baltimore, MD, USA), is somewhat dismissive about his positive role. “It never occurred to me that I was doing anything unusual. It literally, really did not. And it''s only been in the last 10 or 20 years that anyone made much of it,” he said. “If you look back, […] my laboratory [was] very close to [half] men and [half] women.”During the 1970s and 1980s; “[w]hen I entered graduate school,” Greider recalled, “it was a time when the number of graduate students [who] were women was about 50%. And it wasn''t unusual at all.” What has changed, though, is the number of women choosing to pursue a scientific career further. According to the US National Science Foundation (Arlington, VA, USA), women received 51.8% of doctorates in the life sciences in 2006, compared with 43.8% in 1996, 34.6% in 1986, 20.7% in 1976 and 11.9% in 1966 (www.nsf.gov/statistics).In fact, Gall suspects that biology tends to attract more women than the other sciences. “I think if you look in biology departments that you would find a higher percentage [of women] than you would in physics and chemistry,” he said. “I think […] it''s hard to dissociate societal effects from specific effects, but probably fewer women are inclined to go into chemistry [or] physics. Certainly, there is no lack of women going into biology.” However, the representation of women falls off at each level, from postdoc to assistant professor and tenured professor. Cech estimated that only about 20% of the biology faculty in the USA are women.“[It] is a leaky pipeline,” Greider explained. “People exit the system. Women exit at a much higher proportion than do men. I don''t see it as a [supply] pipeline issue at all, getting the trainees in, because for 25 years there have been a great number of women trainees.“We all thought that with civil rights and affirmative action you''d open the doors and women would come in and everything would just follow. And it turned out that was not true.”Nancy Hopkins, a molecular biologist and long-time advocate on issues affecting women faculty members at the Massachusetts Institute of Technology (Cambridge, MA, USA), said that the situation in the USA has improved because of civil rights laws and affirmative action. “I was hired—almost every woman of my generation was hired—as a result of affirmative action. Without it, there wouldn''t have been any women on the faculty,” she said, but added that: “We all thought that with civil rights and affirmative action you''d open the doors and women would come in and everything would just follow. And it turned out that was not true.”Indeed, in a speech at an academic conference in 2005, Harvard President Lawrence Summers said that innate differences between males and females might be one reason why fewer women than men succeeded in science and mathematics. The economist, who served as Secretary of Treasury under President William Clinton, told The Boston Globe that “[r]esearch in behavioural genetics is showing that things people previously attributed to socialization weren''t [due to socialization after all]” (Bombardieri, 2005).Some attendees of the meeting were angered by Summers''s remarks that women do not have the same ‘innate ability'' as men in some fields. Hopkins said she left the meeting as a protest and in “a state of shock and rage”. “It isn''t a question of political correctness, it''s about making unscientific, unfounded and damaging comments. It''s what discrimination is,” she said, adding that Summers''s views reflect the problems women face in moving up the ladder in academia. “To have the president of Harvard say that the second most important reason for their not being equal was really their intrinsic genetic inferiority is so shocking that no matter how many times I think back to his comments, I''m still shocked. These women were not asking to be considered better or special. They were just asking to have their gender be invisible.”Nonetheless, women are making inroads into academia, despite lingering prejudice and discrimination. One field of biology that counts a relatively high number of successful women among its upper ranks is developmental biology. Christiane Nüsslein-Volhard, for example, is Director of the Max Planck Institute for Developmental Biology in Tübingen, Germany, and won the Nobel Prize for Physiology or Medicine in 1995 for her work on the development of Drosophila embryos. She estimated that about 30% of speakers at conferences in her field are women.…for many women, the recent Nobel Prize for Greider […] and Blackburn […] therefore comes as much needed reassurance that it is possible to combine family life and a career in scienceHowever, she also noted that women have never been the majority in her own lab owing to the social constraints of German society. She explained that in Germany, Switzerland and Austria, family issues pose barriers for many women who want to have children and advance professionally because the pressure for women to not use day care is extremely strong. As such, “[w]omen want to stay home because they want to be an ideal mother, and then at the same time they want to go to work and do an ideal job and somehow this is really very difficult,” she said. “I don''t know a single case where the husband stays at home and takes care of the kids and the household. This doesn''t happen. So women are now in an unequal situation because if they want to do the job, they cannot; they don''t have a chance to find someone to do the work for them. […] The wives need wives.” In response to this situation, Nüsslein-Volhard has established the CNV Foundation to financially support young women scientists with children in Germany, to help pay for assistance with household chores and child care.Rhodes, an Italian native who grew up in Sweden, agreed with Nüsslein-Volhard''s assessment of the situation for many European female scientists with children. “Some European countries are very old-fashioned. If you look at the Protestant countries like Holland, women still do not really go out and have a career. It tends to be the man,” she said. “What I find depressing is [that in] a country like Sweden where I grew up, which is a very liberated country, there has been equality between men and women for a couple of generations, and if you look at the percentage of female professors at the universities, it''s still only 10%.” In fact, studies both from Europe and the USA show that academic science is not a welcoming environment for women with children; less so than for childless women and fathers, who are more likely to succeed in academic research (Ledin et al, 2007; Martinez et al, 2007).For Hopkins, her divorce at the age of 30 made a choice between children or a career unavoidable. Offered a position at MIT, she recalled that she very deliberately chose science. She said that she thought to herself: “Okay, I''m going to take the job, not have children and not even get married again because I couldn''t imagine combining that career with any kind of decent family life.” As such, for many women, the recent Nobel Prize for Greider, who raised two children, and Blackburn (Fig 3), who raised one, therefore comes as much needed reassurance that it is possible to combine family life and a career in science. Hopkins said the appearance of Greider and her children at the press conference sent “the message to young women that they can do it, even though very few women in my generation could do it. The ways in which some women are managing to do it are going to become the role models for the women who follow them.”Open in a separate windowFigure 3Elizabeth Blackburn greets colleagues and the media at a reception held in Genentech Hall at UCSF Mission Bay to celebrate her award of the Nobel Prize in Physiology or Medicine. © University of California, San Francisco 2009. Photo: Susan Merrell.     

Chinese hamster telomeres are comparable in size to mouse telomeres.

We report here the results of a telomere length analysis in four male Chinese hamsters by quantitative fluorescence in situ hybridization (Q-FISH). We were able to measure telomere length of 64 (73%) of 88 Chinese hamster telomeres. We could not measure telomere length in chromosome 10 or in the short arms of chromosomes 5, 6, 7 and 8 because of the overlaps between the interstitial and terminal telomeric signals. Our analysis in the 73% of Chinese hamster telomeres indicate that their average length is approximately 38 kb. Therefore, Chinese hamster telomeres are comparable in length to mouse telomeres, but are much longer than human telomeres. Similar to previous Q-FISH studies on human and mouse chromosomes, our results indicate that individual Chinese hamster chromosomes may have specific telomere lengths, suggesting that chromosome-specific factors may be involved in telomere length regulation.     

Testing time for telomeres

Our knowledge of the importance of telomeres to health and ageing continues to grow. Some scientists are therefore commercializing their research, whereas others believe we need an even deeper understanding before we can interpret the results.After 30 years of research, the analysis of telomere length is emerging as a commercial biomarker for ageing and disease, as well as a tool in the search for new medications. Several companies offer tests for telomere length, and more are due to launch their products shortly. Even so, and despite the commercial enthusiasm, interpreting precisely what an individual''s telomeres mean for their health and longevity remains challenging. As a result, there is some division within the research community between those who are pushing ahead with ventures to offer tests to the public, and those who feel that telomere testing is not yet ready for prime time.Peter Lansdorp, a scientist at the British Columbia Cancer Agency and a professor at the University of British Columbia (Vancouver, Canada), founded his company, Repeat Diagnostics, in response to the number of questions and requests he received from physicians for tests for telomere length. The company became the first to offer commercial telomere testing in 2005 and now mainly serves medical researchers, although it makes its test available to the public through their physicians for C $400. Nevertheless, Lansdorp thinks that testing is of limited use for the public. “Testing [...] outside the context of research studies is in my view premature. Unfortunately I think some scientists are exploiting it,” he said. “At this point, I would discourage people from getting their telomeres tested unless there are symptoms in the family that may point to a telomere problem, or a disease related to a telomere problem. I don''t see why on Earth you would want to do that for normal individuals.”“Testing [...] outside the context of research studies is in my view premature. Unfortunately I think some scientists are exploiting it”Others are more convinced of the general utility of telomere tests, when used in combination with other diagnostic tools. Elizabeth Blackburn, Professor of Biology and Physiology at the University of California (San Francisco, USA), was a co-recipient of the Nobel Prize for Physiology or Medicine in 2009 for her part in the discovery of telomerase, the enzyme that replenishes telomeres (Sidebar A). She stressed that the point of telomere testing is to obtain an overall picture “using a marker that integrates many inputs, and produces a robust statistical association with [...] disease risks. It is not a specific diagnostic.” Telome Health, Inc. (Menlo Park, California, USA)—the company that Blackburn helped found and that she now advises in a scientific capacity—plans to begin selling its own US $200 telomere test later this year. “The science has been emerging at a rapid pace recently [...] for those who are familiar with the wealth of the evidence and the accumulated data, the overwhelming pattern is that there are clear associations with telomere maintenance, including longitudinal patterns, and health measures that have had well-tested clinical relevance,” she explained.

Sidebar A | Telomeres and telomerase

Telomeres are regions of repetitive DNA sequence that prevent the DNA replication process or damage from degrading the ends of chromosomes, essentially acting as buffers and protecting the genes closest to the chromosome ends. Russian biologist Alexei Olovnikov first hypothesized in the early 1970s that chromosomes could not completely replicate their ends, and that such losses could ultimately lead to the end of cell division (Olovnikov, 1973). Some years later, Elizabeth Blackburn, then a postdoctoral fellow in Joseph Gall''s lab at Yale University (New Haven, Connecticut, USA), and her colleagues published work suggesting that telomere shortening was linked with ageing at the cellular level, affected lifespan and could lead to cancer (Blackburn & Gall, 1978; Szostak & Blackburn, 1982). In 1984, Carol Greider, working as a postdoc in Blackburn''s lab at the University of California (Berkeley, USA), discovered telomerase, the enzyme that replenishes telomeres. Blackburn and Greider, together with Jack Szostak, were awarded the 2009 Nobel Prize in Physiology or Medicine for “the discovery of how chromosomes are protected by telomeres and the enzyme telomerase” (http://nobelprize.org/nobel_prizes/medicine/laureates/2009/).María Blasco, Director of the Centro Nacional de Investigaciones Oncológicas (CNIO; Spanish National Cancer Research Centre; Madrid, Spain), is similarly optimistic about the prospect of telomere testing becoming a routine health test. “As an analogy, telomere length testing could be similar to what has occurred with cholesterol tests, which went in [the] early 80s from being an expensive test for which no direct drug treatment was available to being a routine test in general health check-ups,” she said.Carol Greider, Professor and Director of Molecular Biology and Genetics at Johns Hopkins University (Baltimore, Maryland, USA) and co-recipient of the 2009 Nobel Prize with Blackburn, however, does not believe that testing is ready for widespread use, although she agreed that telomere length can reveal a lot about disease and is an important subject for research. “Certainly, right now, I think it''s very premature to be offering this kind of testing to the public. I don''t think that the research has yet told us about the risks, what we can actually say statistically with high confidence, so it''s unclear to me if there is any real value to the general public to testing telomeres,” she said.Blasco is Chief Scientific Advisor to Life Length, a CNIO spin-off company that launched its test last year to a storm of media attention. “For some scientists, there is always a question that needs to be solved or has not been sufficiently evaluated,” she said. “We have lots of information showing that telomere length is important for understanding ageing and certain diseases [...] New technologies have been developed that allow us now to measure telomere length in a large scale using a simple blood sample or a spit sample. The fact that the technology is here and the science is here makes this a good moment to market this testing.”“We have lots of information showing that telomere length is important for understanding ageing and certain diseases [...] the technology is here and the science is here”Apart from discussion of the science, companies that offer telomere testing are also encountering scepticism from ethicists and other scientists about the value of telomere-length testing for normal healthy people.Lansdorp, who is a medical doctor by training, thinks that practitioners are not yet ready to use and interpret the tests. “It''s a new field and there are good clinical papers out there, but the irony is that our work [that] has highlighted the value of these tests for specific clinical conditions [is] now being used [...] to make the point that it''s really important to have your telomeres tested, but the dots are not connected by a straight line,” he said.Jonathan Stein, Director of Science and Research at SpectraCell Laboratories (Houston, Texas, USA)—which offers its US $250 telomere test as an extension of its nutritional product line that is sold to family physicians, chiropractors and naturopaths—said that there has only really been demand for the telomere test from his company among physicians and their spouses, but not for use in the clinic. “Doctors are incredibly curious about [the test] and then when we do follow-ups in general, they tell us it''s interesting and they know it''s valuable, but they''re not entirely sure what it means to people. Where we go from the bench to bedside, there seems to be a real sticking point,” he said, adding that he thinks demand will increase as the public becomes increasingly educated about telomeres and health.Arthur Caplan, Professor of Bioethics and Director of the Center for Bioethics at the University of Pennsylvania (Philadelphia, USA), is not clear that even an educated public will be interested in what the test can tell them. “We don''t have any great reason to think that people will be interested in knowing facts about themselves [...] if they can''t do anything about it. I think most people would say ''I''m not going to spend money on this until you tell me if there''s something I can do to slow this process or expand my life''.” As such, he thinks that companies that are getting in early to ''cash in'' on the novelty of telomere testing are unlikely to see huge success, partly because the science is not yet settled.Calvin Harley, President and Chief Science Officer at Telome Health, disagrees. He thinks that two things will drive demand for telomere testing: the growing number of clinical studies validating the utility of the test, and the growing interest in lifestyle changes and interventions that help to maintain telomeres....two things will drive demand for telomere testing: the growing number of clinical studies [...] and [...] interest in lifestyle changes and interventions that help maintain telomeresBut these are early days. Jerry Shay, Professor of Cell Biology and Neuroscience at the University of Texas Southwestern Medical Center (Dallas, USA) and an adviser to the company Life Length, said that early adopters are likely to be the health conscious and the curious. “Some people will say, ''Well, look, I had my telomeres measured: I''m a 60 year old with 50-year-old telomeres'',” he explained. “It will have ''My telomeres are longer than your telomeres'' type of cocktail talk appeal. That''s fine. I have no problem with that as long as we can follow this sort of population and individuals over decades.”“It will have ''My telomeres are longer than your telomeres'' type of cocktail talk appeal [...] I have no problem with that as long as we can follow this sort of population and individuals...”Shay''s last point is the key—research and data collection. Even those commercializing telomere-length tests agree that our understanding of telomere biology, although extensive, is incomplete and that we have yet to unpick fully the links between telomeres and disease. Stefan Kiechl, a telomere researcher in the Department of Neurology at Innsbruck Medical University (Austria), published an article last year on telomere length and cancer (Willeit et al, 2010). “The appealing thing with telomere length measurements is that they allow the estimation of the biological—in contrast to the chronological—age of an organism. This was previously not possible. Moreover, long telomere length has been linked with a low risk of advanced atherosclerosis, cardiovascular disease and cancer, and, vice versa, short telomere length is associated with a higher risk of these diseases.”But, he said that problems remain to be resolved, such as whether telomere length can only be measured in cells that are readily available, such as leukocytes, and whether telomere length in leukocytes varies substantially from telomere length in other tissues and cells. “Moreover, there is still insufficient knowledge on which lifestyle behaviours and other factors affect telomere length,” he concluded.This might be a bumpy road. When Life Length announced its launch in May, newspapers carried headlines such as ''The £400 test that tells you how long you''ll live'', reporting: “A blood test that can show how fast someone is ageing—and offers the tantalizing possibility of estimating how long they have left to live—is to go on sale to the general public in Britain later this year” (Connor, 2011).The story was catchy, but Life Length officials are determined to explain that, despite the name of the company, its tests do not predict longevity for individuals. Blasco said that the word ''life'' in the name is meant as an analogy between telomeres and life. “A British newspaper chose to use this headline, but the company name has no intention to predict longevity,” she said. Instead, the name refers to extensive research correlating the shortened chromosome tips with the risk for certain diseases and personal habits, such as smoking, obesity, lack of exercise and stress, Blasco explained.Life Length''s test measures the abundance of short telomeres, as they claim that there is genetic evidence that short telomeres are the ones that are relevant to disease. “The preliminary results are exciting: we are observing that the percent of short telomeres with increasing age is more divergent between individuals than average telomere length for the same group of individuals,” Blasco explained. “This is exactly what you would expect from a parameter [abundance of short telomeres] that reflects the effects of environmental factors and lifestyle on people''s telomeres.” She noted that being in a lower quartile of average telomere length and the higher quartile of abundance of short telomeres would indicate that telomeres are shorter than normal for a given age, which has been correlated with a higher risk of developing certain diseases.So, what can be done about an abundance of short telomeres? Lansdorp said that, as a physician, he would be hard pressed to know what to tell patients to do about it. “The best measure of someone''s age and life expectancy is the date on their birth certificate. Telomere length, as a biomarker, shows a clear correlation with age at the population level. For an individual the value of telomere length is very limited,” he said. “I suspect there''s going to be a lot of false alarms based on biological variation as well as measurement errors using these less accurate tests.”“The best measure of someone''s age and life expectancy is the date on their birth certificate. [...] For an individual the value of telomere length is very limited”Harley, however, said that if telomere length were perfectly correlated with age, it would be a useless biomarker, except for in forensic work. “The differences in telomere length between individuals at any given age is where the utility lies [...] people with shorter telomeres are at higher risk for morbidity and mortality. In addition, there is emerging data suggesting that people with shorter telomeres respond differently to certain drugs than people with longer telomeres. This fits into the paradigm of personalized medicine,” he said....if telomere length were perfectly correlated with age, it would be a useless biomarker, except for in forensic workWhile he was at Geron Corporation, Harley was the lead discoverer of telomerase activators purified from the root of Astragalus membranaceus. Harley, Blasco and colleagues have published two peer-reviewed papers on one of those molecules, TA-65—one in humans and the other in mice (de Jesus et al, 2011; Harley et al, 2011). Both showed positive effects on certain health measures, and Blasco''s lab found that mice treated with TA-65 had improved health status compared with those given a placebo. “However, we did not see significant effects on longevity,” Blasco said.In the meantime, researchers are squabbling about the techniques used by the testing companies. Greider maintains that Flow-FISH (fluorescence in situ hybridization), which was developed by Lansdorp, is the gold standard used by clinical researchers and that it is the most reliable technique. Harley argues that the quantitative real-time (qRT)-PCR assay developed by the Blackburn lab is just as reliable, and easier to scale-up for commercial use. Blasco pointed out that, similarly to its rivals, the qFISH used by Life Length offers measurements of average telomere length, but that it is the only company to report the percentage of short telomeres in individual cells. In the end, Lansdorp suggested that the errors inherent in the tests, along with biological variations and cost, should give healthy people pause for thought about being tested.Ultimately, whichever test for telomere length is used and whatever the results can tell us about longevity and health, it is unlikely that manipulating telomere length will unlock the fountain of youth, à la Spanish explorer Juan Ponce de León y Figueroa (1474–1521). Nevertheless, telomere testing could become a key diagnostic tool for getting a few more years out of life, and it could motivate people to follow healthier lifestyles. As Kiechl pointed out, “[t]here is convincing evidence that calculation of an individual''s risk of cardiovascular disease [...] substantially enhances compliance for taking medicines and the willingness to change lifestyle. Knowing one''s biological age may well have similar favourable effects.”     

Those dam-aged telomeres!

Telomere integrity plays a crucial role in the capacity for continuous cell proliferation. In some circumstances, shortened telomeres contribute to cell arrest or death, but in others, shortened telomeres may actually enhance the incidence and spectrum of tumors. Resolution of this apparent paradox requires a more detailed understanding of a non-functional telomere. Recent evidence reveals that critically shortened or uncapped telomeres share molecular hallmarks of damaged DNA. It is likely that the cellular response to this DNA damage, influenced by the nature of the damage itself, affects the outcome of loss of telomere function.