Understanding how telomere length affects disease risk later in life

BUFFALO, N.Y. – We don’t often, if ever, associate babies with aging. They may have adorable wrinkles, but those aren’t the same as the ones frequently associated with, say, an octogenarian.

But the reality is that biological aging is happening shortly after (or even before) birth – it’s just occurring in cells, such as the ends of chromosomes known as telomeres. Think of telomeres like an aglet, the short sheath of plastic or metal that keeps the end of a shoelace from fraying.

Just like the end of your shoelace might shrink or fray over time, so, too, do telomeres. They are a marker of biological aging. In fact, shorter telomere length has been associated with many diseases, including cardiovascular disease, as well as death.

Funded by the National Heart, Lung, and Blood Institute — part of the National Institutes of Health (NIH) — a University at Buffalo researcher is examining how early-life factors such as growth patterns and exposure to air pollution affect telomere length from birth to young adulthood. The five-year, $2.6 million project is also looking at how telomere length can impact measures of subclinical atherosclerosis, the underlying cause of heart attack and stroke.

“I think a lot about why people have different telomere length. If we know this answer, maybe we can better understand how to prevent biological aging and some age-related diseases,” says Zhongzheng “Jason” Niu, PhD, the principal investigator on the study and an assistant professor in the Department of Epidemiology and Environmental Health in UB’s School of Public Health and Health Professions.

“Our findings will inform how early changes in biological aging markers may respond to growth and environmental stressors and may subsequently influence the development of aging-related diseases, ultimately offering innovative treatment and prevention strategies to transform public health approaches, targeting the early-life origins of disease with the aim of extending healthy lifespan,” says Niu.

In recent years, scientists have begun to learn much more about telomere length, most notably, that the difference in telomere length between two people may already be distinguishable at birth and amplified as they grow up. Studies have also found that telomere length shortens much faster in childhood than later life, and that it is responsive to many environmental factors, including air pollution.

Niu’s previous work revealed that telomere length at birth is associated with risk for atherosclerosis — the condition in which fatty deposits called plaque accumulate in the artery walls — in midlife. With this current research project, Niu and his team are obtaining more data to quantify telomere length not only at birth but through childhood to adulthood.

“Telomere length trajectory from birth to early adulthood lays the foundation for future telomere length, and this may be associated with future risk of diseases,” says Niu. “This trajectory helps us to understand how telomere length changes in this critical period of life.”

Research has also shown that exposure to air pollution may shorten a person’s telomere length. However, Niu points out, most of these studies examined telomere length at only one point in time, a snapshot that may be explained by numerous other factors besides air pollution.

Niu’s study will contribute new evidence by examining telomere length trajectory. His team will use data on air pollution from conception to 25 years, enabling the researchers to explore if there are periods when people’s telomere length may be more susceptible to air pollution, such as in the uterus, during infancy or perhaps puberty.

“Our project tackles a typically older age disease, atherosclerosis, by examining early-life biological mechanisms and determinants,” Niu says. “The findings may change how people think of and prevent aging-related diseases.”

It is also unique in that another major component of the project involves the repeated measure of subclinical atherosclerosis by taking ultrasound measures of how thick the blood vessel wall is, known as intima media thickness (IMT). Higher IMT can be indicative of atherosclerosis.

“Our study is among the very few that has repeatedly measured IMT in the same person from childhood into adulthood,” Niu explains, adding that alone will fill important gaps in scientists’ understanding of how atherosclerosis develops before any symptoms arise.

By linking telomere length trajectory to IMT changes, Niu and his team hope to answer an important question: As a biomarker of aging, does telomere length trajectory in early life shift the subclinical development of atherosclerosis?

“If the answer is yes, we may need to rethink how we prevent heart disease,” Niu says, “because if the disease process is already shifting in early life through biological aging processes, perhaps we need to allocate more resources toward helping children grow healthier and breathe cleaner air.”

Niu’s study collaborators include Lili Tian, PhD, professor and associate chair of biostatistics at UB; Carrie Breton, ScD, professor, Washington University in St. Louis School of Public Health; Shohreh Farzan, PhD, associate professor of population and public health sciences, and Rima Habre, ScD, associate professor of population and public health sciences and spatial sciences, both in the Keck School of Medicine at the University of Southern California.