In the 2006 film The Holiday, actress Cameron Diaz, playing a woman whose life is spiraling out of control, says: “Severe stress … causes the DNA in our cells to shrink until That they can’t repeat anymore. So when we’re under stress we look lethargic.”
Hollywood got that science right. The DNA to which Diaz’s character points is the segment that forms telomeres, the structures that cap and protect the ends of chromosomes. She was referring to our 2004 publication 1 – the first to link chronic psychological stress to compromised telomere maintenance.
Since that paper, researchers have consistently found that different types of chronic stress are associated with – and probably cause – shorter telomeres. Meanwhile, telomere shortening and stress are both independently associated with several common conditions, such as heart disease and diabetes.
These associations are so broad and consistent that the message is clear even without a detailed understanding of the biochemical pathways involved. Failure to mitigate the severe stress caused by prolonged threats such as war, financial hardship, abuse and emotional neglect, especially in children, will result in increasingly high costs down the line, personal, economic and otherwise.
Human telomeres are several kilobases of repetitive sequences of DNA bound by special protective proteins. A feature of the DNA-replication mechanism is the shortening of telomeres as cells divide. Sometimes the enzyme telomerase can make up for lost DNA, but as we age, our telomeres shorten.
If they become too short, due to aging or because telomere maintenance is disturbed, cells can stop dividing. Such cells also get damaged. For example, they may begin to secrete factors that cause inflammation or trigger tumor growth.
In 2004, we compared telomere length in the white blood cells of mothers of chronically ill children with those of mothers of healthy children. The longer a woman spent being the main caregiver of her sick child (children’s conditions ranged from gut disorders to autism), the shorter her telomeres were.
Furthermore, in both groups, the more severe her psychological stress—as evidenced by her answers to standardized questions, for example, how much control she felt over her life—the shorter her telomeres. The ‘most stressed’ mothers (compared to the ‘least stressed’ mothers) had additional telomere shortening equivalent to at least a decade of aging.
The relationship between stress and telomere length continues to be visible: a study of kindergarten-aged children to adults up to age 80; From small clinical samples of less than 100 people to large population-based samples of thousands,3 .
Under stress, the body accelerates the production of certain hormones, such as cortisol, and other biochemical factors. These compounds help to mediate the appropriate response to short-term stress. But when produced in excess for months or years, they can alter gene expression, possibly with harmful effects (see page 171).
In the laboratory, the same factors can shorten telomeres—in the case of cortisol, by reducing the activity of telomerase. It is likely that pathways mediating changes in gene expression interact with those affecting telomere maintenance, although this remains to be explored.
Although several studies have explored (and continue to uncover) links between stress and shortened telomeres, others have forged links between telomere shortening and common disorders. Rare mutations of genes encoding components of telomerase cause telomeres to become very short.
This results in immune-system disorders such as aplastic anemia, and other conditions including pulmonary fibrosis, diabetes, some heart diseases, and some cancers. Remarkably, many of these inherited diseases, more recently named ‘telomere syndromes’, are those most commonly associated with aging.
Telomere shortening can also predict people’s statistical risk of developing certain conditions. For example, after 10 years of having their telomeres measured, men and women with shorter telomeres were three times more likely to develop certain types of cancer, such as pancreatic cancer. If the elderly, people with shorter telomeres were also 50% more likely to develop dementia and 50% more likely to die from a specific cause than those with longer telomeres.
Evidence that lifestyle, well-being and other environmental factors can contribute significantly to disease has been accumulating for decades.
But now we have three pair-wise links involving three factors: tension with telomere shortening; stress with disease risk; And with the risk of these diseases comes telomere shortening. It is hard to avoid the conclusion that stress is at least one of the ways in which chronic diseases cause telomeres to shorten.