CHICAGO—Telomere length is considered an important biomarker in human aging and disease, but most studies on the relationship between telomere length and health have only looked at a single tissue type — blood. This limitation raised questions of whether blood cells are a reliable proxy for other tissues.
“Most studies on human telomere length focus on tissue types that are easy to collect from living subjects, like whole blood or saliva,” said Kathryn Demanelis, Ph.D., a postdoctoral scholar in the Department of Public Health Sciences at the University of Chicago and first author of a new study. “We wanted to see how well the length of telomeres found in whole blood cells aligned with those found in other tissues.”
The study, which was published in Science, has examined telomere length in 23 different human tissue types from nearly 1,000 individual post-mortem donors. The results show that indeed, telomere length in whole blood can serve as a stand-in for telomere length in many other tissues. This research also bolsters existing research on the relationship between telomere length, ancestry and aging.
Aging is associated with telomere shortening, and telomere shortening has been linked to mortality and age-related diseases. But the relationship between telomere shortening, aging and disease isn’t entirely clear — partly because the ways in which telomeres vary between different tissue types aren’t fully understood.
For this study, the scientists took advantage of the Genotype-Tissue Expression (GTEx) project, a massive public resource focused on collecting samples from many different tissues from hundreds of human subjects.
“The GTEx study was originally designed to study how inherited genetic variation regulates gene activity in different tissues, and how tissues differ from one another. We saw the GTEx tissue bank as an opportunity to access tissue types that we normally can’t study easily, and to look at an important biomarker — telomere length — and start to ask deeper questions about the relationship between telomere length and diseases like lung cancer, and how telomeres shorten with age in different kinds of tissue,” noted senior author Brandon Pierce, Ph.D., associate professor of Public Health Sciences and Human Genetics at University of Chicago.
The researchers used a new type of assay for measuring telomere length that was comparable in cost to traditional methods but more precise, with higher throughput.
“We were able to find statistically significant tissue-to-tissue differences in telomere length within the sample set,” added study co-author Muhammad Kibriya, M.D., Ph.D., research associate professor at the Institute for Population and Precision Health at University of Chicago.
Investigators compared telomere length in skin, brain, lung, colon and kidney tissues to telomere length in blood cells. They found that out of the 23 tissues studied, telomere length in 15 tissues showed a clear, positive correlation with telomere length in whole blood cells. This information supports the use of whole blood cell telomere length as a proxy for telomere length in harder to access tissues like brain and kidney.
“We were also able to look across all of these tissue types to answer questions that have been looked at repeatedly for blood cell telomeres,” Pierce pointed out. “Some patterns held up across different tissues, like shorter telomeres in aging and longer telomeres in people of African ancestry, but others didn’t, like longer telomeres in females. We observed shorter telomeres among smokers in only a few tissues.”
This clarifies conflicting results from past studies indicating relationships between individual traits and telomere length, or a lack thereof. The results will help elucidate which aspects of telomere length are consistently due to genetic inheritance, versus those that could be affected by lifestyle, environmental exposures or epigenetic changes during a person’s lifetime.
“As epidemiologists, we’re often trying to answer questions by studying blood samples, so we have to be aware of how these biomarkers might vary across different tissue types. It’s a big limitation. But we know that the inherited genome sequence is the same in every tissue, so if we can understand how certain genetic variations affect biomarkers like telomere length in specific tissue types, that makes it easier to study those biomarkers in human populations,” continued Pierce. “We can use inherited genetic variation to predict tissue-specific biomarkers.”
“This first study provides a resource to better understand what telomere length looks like in various tissues and will allow other researchers to compare their data against our results,” Demanelis concluded. “In the future, we’ll be looking at other markers like DNA methylation and somatic mutations in different types of tissues to try and understand their relationship to telomere length and aging.”