Telomeres Hold Considerable Sway Over Our Health

Telomeres, the DNA that cap the ends of our chromosomes, play a central role in the longevity of our cells, and they may also affect and be affected by psychiatric disorders, said Elizabeth Blackburn, Ph.D., at APA’s annual meeting in San Francisco in May.

David Hathcox

Left to their own devices, telomeres shorten with each cell division. Compromising telomere maintenance eventually impairs the cell replenishment and function. When they get too short, the cell ceases to divide, senescence sets in, and the cell puts out pro-inflammatory and tumorigenic factors, said Blackburn, a professor of biochemistry and biophysics at the University of California, San Francisco.

This wreaks havoc in the neighborhood, she said. “They’re like a rotten apple in a barrel, affecting the other cells around them.”

But humans live for decades, so something must counteract those ever-shrinking telomeres. That something is the enzyme telomerase. Discovering how telomeres and telomerase protect chromosomes led to the Nobel Prize in Physiology or Medicine in 2009 for Blackburn, Carol Greider, Ph.D., and Jack Szostak, Ph.D.

Telomerase acts to counter telomere shortening in cell division, said Blackburn. “Telomerase is trying to ‘rescue’ telomeres as they get too short.”

Given its critical role in physiology, telomerase is under “exquisite and tight control at every level of control you can think of,” said Blackburn. These include transcription, RNA splicing, assembly of ribonuclear proteins, trafficking, signaling inputs, and post-transcriptional modification.

Such control is important because telomerase abides by the Goldilocks principle. Too little allows telomeres to get shorter, but a combination of short telomeres and high telomerase levels is associated with worse health outcomes including risk of depression and cancer.

Telomere maintenance integrates many inputs, both genetic and nongenetic.

A broad range of environmental stressors can affect telomere length and the risk of mortality and morbidity: intrauterine stress, traumatic childhood events, lifetime duration of depression, and low educational attainment.

Perturbation in telomere maintenance, whether by causation or association, is linked to many age-related disorders, she said.

“Telomere length is both a cause or contributor to and a marker of disease,” said Blackburn. For instance, people with one rare, extreme mutation (dyskeratosis congenita) have higher rates of neuropsychiatric morbidity.

However, more complex relationships exist, as well.

Bladder cancer patients with both depression and short telomeres have an average survival of 31 months, compared with 60 months for those with depression alone and 200 months for those with neither condition.

Another study found that mothers stressed by caring for chronically ill children had shorter immune-cell telomere lengths. And the Whitehall study in Britain reported that “cynical hostility” was related to telomere shortness, Blackburn said.

A study of 100,000 Kaiser Permanente patients that included 20 years of clinical data, surveys, interviews, and environmental exposure data found higher risks of mortality in the lowest versus the highest quartile of telomere length.

Observational research, she noted, has suggested that short telomeres are associated in the general population with a number of illnesses, including cancers, pulmonary fibrosis, cardiovascular diseases, vascular dementia, and diabetes.

Stress reduction techniques like physical exercise, better sleep quality, or meditation may counteract telomere shortening, but these must be tested in controlled trials, said Blackburn. ■