Biomedical Sciences Blog

On Tuesday, November 16, 2010, part 3 of the Translational Research Seminar Series for Duke postdocs occurred at Duke University (T1 Translation Research is the process of moving from laboratory findings to clinical practice, or "from bench to bedside"). In this session, a moderator and panel discussed the nuts and bolts of forming and maintaining relationships with clinicians that will serve to catalyze the translation of your discoveries to the bedside. Dr. Christy Ahn was joined by 3 panelists who shared their stories of collaborating (successes and hurdles), and who were all open to new research ventures.

Moderator/Lead: Christy Ahn, PhD, Director, Faculty Enrichment Programs, Duke School of Medicine

Panelists:
Dawn Bowles, PhD-Assistant Professor, Department of Surgery, Duke School of Medicine
Herman Staats, PhD: Professor, Department of Pathology, Duke School of Medicine
John Sundy, MD, PhD-Associate Professor, Pulmonary, Allergy, and Critical Care Medicine, Duke Department of Medicine

Ewen Callaway

Premature ageing can be reversed by reactivating an enzyme that protects the tips of chromosomes, a study in mice suggests.

Mice engineered to lack the enzyme, called telomerase, become prematurely decrepit. But they bounced back to health when the enzyme was replaced. The finding, published online today in Nature¹, hints that some disorders characterized by early ageing could be treated by boosting telomerase activity.

It also offers the possibility that normal human ageing could be slowed by reawakening the enzyme in cells where it has stopped working, says Ronald DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, who led the new study. "This has implications for thinking about telomerase as a serious anti-ageing intervention."

Other scientists, however, point out that mice lacking telomerase are a poor stand-in for the normal ageing process. Moreover, ramping up telomerase in humans could potentially encourage the growth of tumours.

Eternal youth

After its discovery in the 1980s, telomerase gained a reputation as a fountain of youth. Chromosomes have caps of repetitive DNA called telomeres at their ends. Every time cells divide, their telomeres shorten, which eventually prompts them to stop dividing and die. Telomerase prevents this decline in some kinds of cells, including stem cells, by lengthening telomeres, and the hope was that activating the enzyme could slow cellular ageing.

Two decades on, researchers are realizing that telomerase's role in ageing is far more nuanced than first thought. Some studies have uncovered an association between short telomeres and early death, whereas others have failed to back up this link. People with rare diseases characterized by shortened telomeres or telomerase mutations seem to age prematurely, although some tissues are more affected than others.

When mice are engineered to lack telomerase completely, their telomeres progressively shorten over several generations. These animals age much faster than normal mice — they are barely fertile and suffer from age-related conditions such as osteoporosis, diabetes and neurodegeneration. They also die young. "If you look at all those data together, you walk away with the idea that the loss of telomerase could be a very important instigator of the ageing process," says DePinho.

To find out if these dramatic effects are reversible, DePinho's team engineered mice such that the inactivated telomerase could be switched back on by feeding the mice a chemical called 4-OHT. The researchers allowed the mice to grow to adulthood without the enzyme, then reactivated it for a month. They assessed the health of the mice another month later.

"What really caught us by surprise was the dramatic reversal of the effects we saw in these animals," says DePinho. He describes the outcome as "a near 'Ponce de Leon' effect" — a reference to the Spanish explorer Juan Ponce de Leon, who went in search of the mythical Fountain of Youth. Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver and intestines, recuperated from their degenerated state.

The one-month pulse of telomerase also reversed effects of ageing in the brain. Mice with restored telomerase activity had noticeably larger brains than animals still lacking the enzyme, and neural progenitor cells, which produce new neurons and supporting brain cells, started working again.

"It gives us a sense that there's a point of return for age-associated disorders," says DePinho. Drugs that ramp up telomerase activity are worth pursuing as a potential treatment for rare disorders characterized by premature ageing, he says, and perhaps even for more common age-related conditions.

Cancer link

The downside is that telomerase is often mutated in human cancers, and seems to help existing tumours grow faster. But DePinho argues that telomerase should prevent healthy cells from becoming cancerous in the first place by preventing DNA damage.

David Sinclair, a molecular biologist at Harvard Medical School in Boston, agrees there is evidence that activating telomerase might prevent tumours. If the treatment can be made safe, he adds, "it could lead to breakthroughs in restoring organ function in the elderly and treating a variety of diseases of aging."

Other researchers are less confident that telomerase can be safely harnessed. "Telomere rejuvenation is potentially very dangerous unless you make sure that it does not stimulate cancer," says David Harrison, who researches ageing at the Jackson Laboratory in Bar Harbor, Maine.

Harrison also questions whether mice lacking telomerase are a good model for human ageing. "They are not studying normal ageing, but ageing in mice made grossly abnormal," he says. Tom Kirkwood, who directs the Institute for Ageing and Health at Newcastle University, UK, agrees, pointing out that telomere erosion "is surely not the only, or even dominant, cause" of ageing in humans.

DePinho says he recognizes that there is more to ageing than shortened telomeres, particularly late in life, but argues that telomerase therapy could one day be combined with other therapies that target the biochemical pathways of ageing. "This may be one of several things you need to do in order to extend lifespan and extend healthy living," he says.

References

• 1. Jaskelioff, M. et al. Nature doi:10.1038/nature09603 (2010).

2011 Call for Applications

The L'Oréal USA Fellowships for Women in Science program announces the 2011 call for applications.

The L’Oréal USA Fellowships for Women in Science program is a national awards program that annually recognizes and rewards five U.S.-based women researchers at the beginning of their scientific careers. Recipients each receive up to $60,000 that must put towards their postdoctoral research.

Launched in 2003 as the U.S. component of the L'Oréal-UNESCO for Women in Science International Fellowship program, the U.S. Fellowships aim to:

• Raise awareness of the contribution of women to the sciences
• Identify exceptional female researchers in the U.S. to serve as role models for younger generations

Candidates who would like to apply may visit: http://lorealfwis.aaas.org. Applications are now being accepted online.

Eligibility Requirements:

• Candidates must be female scientists, who will have completed their Ph.D. by the time of their application submission and have started in a postdoctoral research position by September 1, 2011
• Applicants must be American born, naturalized citizens, or permanent residents
• Applicants must be affiliated with a U.S.-based academic or research institution
• Applicants must conduct their postdoctoral studies and research in the U.S.
• Applicants must be involved in life or physical/material sciences, engineering, technology, computer science or mathematics

The application period will close on December 13, 2010, and awards will be announced by May 2011.

For more information about the Fellowships, visit the L'Oréal USA Fellowships for Women in Science Program webpage.

To view a PDF of the frequently asked questions regarding the program, please click here.


The American Association for the Advancement of Science (AAAS), which is dedicated to advancing science around the world, is the official administrator for the L'Oréal USA Fellowships for Women in Science Program. In this capacity they:

• Process fellowship grants payments
• Collect and review interim and final progress reports
• Facilitate professional networking opportunities for all interested L’Oréal USA Fellowships for Women in Science grant recipients

Background

There is a great social, medical and economic challenge of historic proportion due to the dramatic increase in life expectancy. This welcome increase in survivorship brings with it a higher probability that multiple and interactive health problems, both chronic and acute will occur. Significant breakthroughs in understanding the basic biological processes that underlie aging-related diseases and disorders are the most promising approach to achieving genuine prevention or improvement of age-related debilitation and disease and it is now believed that such breakthroughs in understanding these processes are not only possible, but in fact are the likely consequence of the application of modern biological research techniques.

To pursue this new knowledge, talented investigators must be attracted to aging research. However, given the current funding climate, concerns about an adequate funding base for post-doctoral fellows exist and can be potentially detrimental to the quality of research in the area. We need to continue to nurture the research base that will be necessary to ensure the health of millions of older people. Serious gaps in biomedical and clinical research are placing the healthy aging and independence of older people at risk.

The Program

The Ellison Medical Foundation, in partnership with the American Federation for Aging Research (AFAR), created the Ellison/AFAR Postdoctoral Fellows in Aging Research Program to encourage and further the careers of postdoctoral fellows with outstanding promise in the basic biological and biomedical sciences relevant to understanding aging processes and age-related diseases and disabilities. The award is intended to provide significant support to permit these postdoctoral fellows to become established in the field of aging. Projects concerned with understanding the basic mechanisms of aging will be considered. Projects investigating age-related diseases are also supported, if approached from the point of view of how basic aging processes may lead to these outcomes. Projects concerning mechanisms underlying common geriatric functional disorders are also considered. Projects that deal strictly with clinical problems such as the diagnosis and treatment of disease, health outcomes, or the social context of aging are not eligible.

It is anticipated that up to 15 one-year grants will be awarded in 2011, ranging from $45,218 for a first-year fellow to up to $59,402 for a fellow with more than 7 years of training. Of the award, up to $7,850 may be requested for expenses such as research supplies, equipment, health insurance and travel to scientific meetings.

Recipients of this award are expected to attend the AFAR Grantee Conference; funds will be withheld from the grant for this purpose. The goal of the meeting is to promote scientific and personal exchanges among recent AFAR grantees and experts in aging research.

Eligibility Criteria

• The applicant must be a postdoctoral fellow (MD and/or PhD degree) at the start date of the award (July 1, 2011.) The proposed research must be conducted at any type of not-for-profit setting in the United States. Individuals who are employees in the NIH Intramural program are not eligible.
• Fellows may not hold any concurrent foundation or not-for-profit funding.

Former Ellison/AFAR postdoctoral fellowship awardees may apply if the criteria above are met.

Application Guidelines

The following criteria are used to determine the merit of an application:

• Qualifications of the applicant
• Quality of the proposed research and relevance to aging
• Excellence of the research environment
• Likelihood that the project will advance the applicant's career in aging research
• Mentor's strength and qualifications to guide the applicant's research and career planning
• Proposed training opportunities

If you are using animals in your research, please review Principles of Animal Use for Gerontological Research.

Application Procedures

The deadline for receipt of all applications and supporting materials is December 15, 2010 at 5:00 p.m. EST. Please refer to the Ellison/AFAR instruction sheet and application for complete application procedures. Incomplete applications cannot be considered.

All candidates must submit applications endorsed by their institution. Applications are reviewed in two stages: An initial screening is made by an international team of reviewers after which candidates are advised of the status of their applications via email by mid-April. Proposals that are successful in the initial screening are then reviewed by members of a second committee and final awards are announced by early June. The award start date is July 1, 2011. AFAR can only provide critiques for those applications that went through to the second level of review.

For an application, click here.