The Link Between Childhood Adversity and Cellular Aging

Neglected childAdversity and stress are known risk factors for psychiatric disorders, cardiovascular and immune disease, cognitive decline and other health problems. The long-term negative effects of adversity seem to be greatest if the traumatic events were experienced during childhood, when the brain and other biological systems are developing and maturing. Researchers are working to identify the mechanisms involved and have identified telomere shortening as one possible mechanism by which adversity increases morbidity and mortality.

Telomeres are regions of repetitive DNA that protect the ends of chromosomes from deterioration and fusion with neighboring chromosomes and ensure that genetic information is not lost during cell division. When a cell divides, the entire genome is replicated, and a copy is passed to each daughter cell. However, DNA polymerases cannot replicate DNA at the ends of chromosomes effectively, so chromosomes are shortened each time a cell divides. In essence, telomeres act as sacrificial DNA so that telomere sequences, not functional genes, are lost. Telomere shortening is thought to limit the number of times that a cell can divide. Once telomeres reach a critical length, cellular senescence is triggered, and a cell stops dividing and dies. As a result, telomere length can act as a gauge of cellular age.

Telomere length can be linked to health problems. Short telomeres are associated with premature aging syndromes and some types of cancer. Accelerated telomere shortening, and thus accelerated cellular aging, is more common in people with cardiovascular disease, diabetes, psychiatric disorders and some other health problems.

Telomeres naturally shorten as we age. Researchers have shown that rates of telomere shortening are greatest during infancy and early childhood and that regulation of telomere length may be programmed during early development. Telomere length can be influenced by factors other than age, including heredity, epigenetics and environmental factors such as exposure to radiation, toxins, and oxidative and psychological stress (reviewed in reference 1). Chronic stress, serious illness or neglect during childhood can have lasting effects on telomere length: Adults who were subjected to abuse or neglect as children have significantly shorter telomeres than adults with no history of mistreatment (2). Chronic stress as an adult also can shorten telomeres, as shown in studies of healthy adult females who acted as caregivers of chronically ill people (3,4).

The most recent research on this topic used young children living in Romanian institutions as a model of childhood adversity (5). As part of the Bucharest Early Intervention Program, children between the ages of 6 and 30 months were split into two groups: Some were placed in foster care and some remained at the institution, where they received much less individual attention and lower-quality care and had fewer opportunities for social interaction and a higher risk of malnutrition. Researchers analyzed DNA samples taken from both groups of children and showed that institutionalized children tended to have shorter telomeres and that, in general, the longer a child received institutionalized care, the shorter his telomeres. Although telomere length did not differ significantly by gender, the window of time when adversity had the greatest effect did. For girls, the percent of time spent in an institution at the initial assessment (mean age of 22 months) was more predictive of the reduction in telomere length, as measured during middle childhood, than the percent of time at 54 months. The opposite was true for boys. The percent of time spent at an institution at 54 months had a greater effect than the percent of time at the initial assessment. Knowing that timing can be an important factor allows caregivers to give children the most attention when they are the most vulnerable.

The results of this study lend support to the idea that childhood adversity leads to premature cellular aging and higher risks for health problems later in life. If this is true, what is the biological mechanism?

Scientists have shown that childhood is a period of extensive epigenetic modification of DNA, such as methylation, which can greatly affect gene expression. Children who experience serious adversity exhibit changes in epigenetic modifications—changes that persist long after the adversity is overcome. These changes can even be triggered by prenatal events such as maternal depression. Drury et al. offer a hypothesis to explain the shorter telomeres: Changes in DNA methylation patterns in institutionalized children affect not only gene expression but also telomere length and the rate of telomere shortening.

Thus, these children face a potential epigenetic double whammy of altered gene expression and more advanced cellular age. It is too soon to know exactly what are the long-term health risks because many of these negative effects do not manifest until much later in life, and it is not clear from existing research whether the epigenetic changes are reversible by enriching the child’s environment. To date there have been no lifelong studies with neglected or abused children to show that shortened telomeres during childhood correlate with shortened telomeres and increased health problems in adulthood. Regardless of the biological mechanism, whether it is telomere shortening or something else, the data are clear about one thing: These children face a higher risk of adversity in the future.

References

  1. Shammas, M.A. (2011) Telomeres, lifestyle, cancer, and aging. Cur. Opin. Clin. Nutr. Metab. Care 14, 28–34.
  2. Tyrka, A.R. et al. (2010) Childhood maltreatment and telomere shortening: Preliminary support for an effect of early stress on cellular aging. Biol. Psychiatry 67, 531–4.
  3. Epel, E.S. et al. (2004) Accelerated telomere shortening in response to life stress. Proc. Natl. Acad. Sci. USA 101, 17312–5.
  4. Damjanovic, A.K. et al. (2007) Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. J. Immunol. 179, 4249–54.
  5. Drury, S.S. et al. (2011). Telomere length and early severe social deprivation: Linking early adversity and cellular aging. Mol. Psychiatry epub ahead of print. doi:10.1038/mp.2011.53.
    1. The following two tabs change content below.

      Terri Sundquist

      Terri has worked as a Scientific Communications Specialist at Promega Corporation for more than 13 years, and prior to that, spent more than 5 years solving problems and answering questions as a Promega Technical Services Scientist. She graduated with B.S. degrees in Chemistry and Biology at the University of Wisconsin—River Falls, then earned her M.S. in Molecular Biology from the Mayo Graduate School in Rochester Minnesota.

2 thoughts on “The Link Between Childhood Adversity and Cellular Aging

Leave a Reply