By Elissa S. Epel, The American Journal of Psychiatry, January 1, 2020
There has been growing scientific interest in telomere biology over the 35 years since its fundamental mechanisms were deciphered. Telomeres, the finely regulated protective caps at the tips of our chromosomes, play a critical role in aging, from yeast to humans. Telomeres are made of long, winding strands of repeat sequences of noncoding DNA, covered with protective proteins. Although their regulation and functions are complex, we can summarize their actions related to cell survival: they shorten with cell division and with exposure to biochemical stressors, such as oxidative stress, and when they become critically short or damaged, there is DNA-damage signaling and a menu of actions in place, likely to protect the rest of the genome. The cell can no longer replicate and replenish tissue, and in fact becomes senescent, inflammatory, or apoptotic. Fortunately, the process of telomere shortening is regulated by several factors, mainly telomerase. Telomerase is the special ribonucleoprotein enzyme that can restore telomere length, adding back the base pairs, making telomere length a malleable marker of aging.
Telomeres are good predictors of life span in some species, like birds, and poor predictors in rodents, which are born with very long telomeres. We are still trying to determine exactly how important telomeres are to the physical health, mental health, and life span of humans. So far, more progress has been made on the physical health compared with the mental health side. Unlike many other biomarkers, telomeres play a causal role in aging cells. Clinically short telomeres, caused, for example, by mutated telomerase, prematurely exhaust certain stem cells, contributing to diseases like aplastic anemia, lung fibrosis, and early death. Additionally, having a higher genetic propensity for shorter telomeres, through commonly occurring genetic variants, predicts greater risk of heart disease and dementia. Meta-analyses show that shorter telomeres measured in blood in midlife (and typically not in the elderly years) predict greater risk for earlier mortality. However, it is safe to say that these effects of measured telomeres, and especially the effect sizes of purely genetic loadings for telomeres, while reliable across diverse samples, are small compared with other clinical risk factors.
The importance of long, stable telomeres in relation to the health span makes it critical to understand the malleable nongenetic factors that shape telomere length. Shorter telomeres are reliably associated with psychiatric diseases, especially depression. As reviewed elsewhere, there is now a strong translational research base demonstrating that distress (stressor exposure, stress-induced depression) precedes telomere shortening. In terms of life span health, psychopathology often occurs early in adulthood and precedes and contributes to earlier biological aging and mortality. It is also possible that impaired telomere biology precedes and plays a causal role in psychopathology, as people with telomere-related genetic disorders tend to have psychiatric disorders as well. We do not yet know whether telomeres predict mental health outcomes, although there are suggestions that short telomeres may precede depression.
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