Heacock said the workshop aims were to review the science on links between telomere status and disease susceptibility, as well as to develop research recommendations to strengthen methods. (Photo courtesy of Steve McCaw)

At NIEHS Sept. 6-7, scientific experts discussed the potential of telomeres as valuable markers of exposure to pollutants or stress, and vulnerability to disease. Telomeres are caps on the ends of chromosomes that shorten each time a cell divides. They decrease in length as people age.

The workshop, “Telomeres as Sentinels for Environmental Exposures, Psychosocial Stress, and Disease Susceptibility,” was organized by Michelle Heacock, Ph.D., of the NIEHS Hazardous Substance Research Branch, and Lisbeth Nielsen, Ph.D., of the National Institute on Aging (NIA) Division of Behavioral and Social Research. Both institutes are part of the National Institutes of Health.

“We are here to generate a strong vision for the rapidly developing field of telomere research,” said NIEHS and National Toxicology Program Director Linda Birnbaum, Ph.D., in opening remarks. “There are many questions in the field, and we need to advance collaboratively, basic scientists together with clinicians and epidemiologists.”

Basic scientists are uncovering the details of telomere biology in the laboratory, as clinicians and epidemiologists explore telomere length as a marker of human health. Studies suggest that excessively shortened telomeres may be associated with an increased risk of cardiovascular disease and some degenerative diseases. Extra-long telomeres may be associated with an increased risk of certain cancers. However, these conclusions are far from settled.

Methods for measuring telomere length

Lansdorp said the biggest decline in telomere length occurs early in life, likely because of high turnover of stem cells during early development. (Photo courtesy of Steve McCaw)

The discussion quickly turned to questions of how to precisely and reliably measure telomere length. Some scientists are concerned that differences in results among studies may represent variations in measurement.

“We need to address the questions of method,” said Peter Lansdorp, M.D., Ph.D., of the British Columbia Cancer Agency.

Frequently used techniques include quantitative polymerase chain reaction (qPCR), and a combination of flow cytometry and fluorescent in situ hybridization (Flow-FISH). Although some scientists criticized the potential for error in measurement of telomere length using qPCR, others said it was not credible that measurement error alone would produce the effects on telomere length observed using the method.

Stacy Drury, M.D., Ph.D., of Tulane University, suggested that there needs to be a balance between use of qPCR and Flow-FISH, and close monitoring of the reproducibility of measurements.

Telomere length established in early childhood

One point of consensus at the meeting was that telomere length during childhood is one of the most important determinants of telomere length in adults. This means that some data on telomere length in adults may reflect patterns set in early childhood, unless scientists have the information to control for childhood length, according to Elissa Epel, Ph.D., from University of California at San Francisco.

Pathik Wadhwa, M.D., Ph.D., from the University of California at Irvine, said a person’s telomere length may initially be set in the womb. “There is preliminary evidence that maternal stress and nutrition-related factors during pregnancy may influence telomere length,” he said.

From left, Wadhwa; Drury; Belinda Needham, Ph.D., from University of Michigan; and Idan Shalev, M.D., Ph.D., of Pennsylvania State University, not shown, joined a panel about the effects of stress. (Photo courtesy of Steve McCaw)

There is also evidence that telomere length may be partly inherited, according to Chandra Reynolds, Ph.D., from the University of California at Riverside, and others at the workshop. Abraham Aviv, M.D., from Rutgers University, emphasized that unless scientists account for heritability, for example, by knowing parental telomere lengths, it can be hard to look at the potential effects of environmental factors on telomere length.

In addition, several scientists suggested that exposure to stress or environmental factors like ionizing radiation may have a more damaging effect on telomere length during childhood than during adulthood. According to Epel, this underscores the need to understand the biology of telomere length at different life stages.

Telomere length — a marker of exposures?

Nielsen said that telomeres are of increasing interest in studies that follow people as they age, especially as NIA tries to understand premature aging and the early stages of disease. (Photo courtesy of Steve McCaw)

The question of whether telomere length can serve as a marker of exposure to environmental pollutants and stress remains unsettled. Some scientists proposed that telomeres may indicate vulnerability to environmentally induced disease. Others, who supported the potential for telomere length to be a marker, acknowledged that challenges with measurement need to be resolved.

Colter Mitchell, Ph.D., from the University of Michigan, reflected that developing a new biomarker always involves a lengthy scientific process, starting with initial excitement about the method, then disillusionment as challenges are realized, and then solid methods emerge.

(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison and a regular contributor to the Environmental Factor)