Throughout her paper, Mona El Gendi chemically breaks down the components of telomeres and describes how their size is altered by childhood stress.
Mona El Gendi
Telomeres are caps at the end of eukaryotic chromosomes that protect and prevent chromosomes from losing important information during cellular replication, keep cells viable, and allow proteins to continue to be produced. They are essential for protecting the chromatin from DNA damage during the process of recombination (Palmos et al., 2018). They are made of repetitive DNA or RNA (and sometimes protein) sequences (repeats of bases TTAGGG) that do not code for anything. In most somatic cells, telomeres shorten after each cycle of replication, going through about 60-70 replication cycles before they are considered too short (Coimbra et al., 2017). Once too short, the telomeres reach a point called the “Hayflick limit” where the cell either undergoes apoptosis or enters a stage of cellular senescence in which it can no longer divide, to prevent impending DNA damage and to reduce the risk of cancer. Some cells have an enzyme called telomerase which adds back bases to the telomeres, however, this enzyme is only present in a small portion of cells such as stem cells. Therefore the old cells are incapable of replacing the old, damaged cell, and the body becomes more vulnerable. For most people telomeres decrease with age, therefore they have been used to determine biological age and are established markers of cell stress and aging.
Not only are telomeres considered to be a good biological clock, they are also good biomarkers for susceptibility to various health conditions. According to a 2017 study by Coimbra Et. Al, shortened telomeres have been shown to be a proxy for accelerated aging and having a linkage to death. Health complications that have been linked to shortened telomeres include diabetes mellitus, cardiovascular disease, depression, dementia, osteoarthritis, and many more (Coimbra Et. Al, 2017). In a 2020 study by Esteves et al., telomere length was shown to be influenced by physiological stress, oxidative stress, genotoxic stress, and neuroendocrine hormones (Esteves et al., 2020). Shorter telomere length has also been shown to be associated with environmental stress exposure (Humphries et al., 2018). Now that the importance and detrimental effects of telomere shortening are understood, this paper will explore what the effects of early adversity and life stress are on telomere length and what can be done about it.
Early Life Stress
It goes without saying that difficulties in childhood can psychologically affect an individual
for the rest of their life, however, research is also now showing that early childhood stress can also cause physical health issues as well. Adverse childhood experiences (ACE) and pathophysiology have been proven to have effects on telomere length within and throughout generations that in turn cause physical complications (Esteves et al., 2020). Life adversity is a broad notion and can come in different forms such as maternal depression, violence, low socioeconomic status, family disruption, institutionalization, and more (Coimbra et al., 2017). A study in 2017 examined the association between stress and telomere length in children ages three to fifteen. These various types of stress can also be intertwined as children can and usually are affected by more than one. One review concluded that low socioeconomic status accelerates cellular aging in children. Furthermore, the children with the worst economic situations had the greatest amount of rapid telomere erosion (Coimbra et al., 2017). Similarly, in 2018, Gerritsen et. Al published a 25 year-old longitudinal study where the early and late life stress and their effects were compared between twins. The study found that participants with early life stress showed a significantly steeper decline in the length of their leukocyte telomeres (LTL) at around the age of 69. Leukocytes, also known as white blood cells, make up the immune system thus their premature senescence can potentially act as an indicator of abnormalities in the body. When zooming into the monozygotic twin pairs the study found that, specifically early life stress, has a notable influence on accelerated LTL decline both before and after the age of 69 while later life stress did not have a significant decrease in LTL. Their findings suggest that early life stress is more consequential and has longer lasting effects in comparison to later life stress (Gerritsen Et. Al, 2018).
As mentioned earlier, life adversity is a rather general term and there are many different types of stress that can affect a child. An important one to look at is stress caused by parents as they play a large role in the development of a child. Through looking at salivary telomere length, a study in 2017 by Mitchell et al., was done to investigate how father loss influences telomere length. The study determined that at the age of nine children with father loss had about a 14% reduction in the length of their telomeres. Something to note is that there are different types of father loss, the study specifically found that paternal death has the largest association (16%), followed by incarceration (10%), and separation and/or divorce (6%) to telomere shortening. In addition, the study explains that though the children were all missing their fathers, the main stressor, indirectly, was the income loss and that is what explains the shortening of telomeres for most of the children (Mitchell et al., 2017). Income loss can have a tremendous impact on many different aspects of a child's life including their education, time spent with others, relationships with their parents, nutrition, and many others thus it can be categorized as a stressor.
Besides direct stress to the child's life, early life adversity caused by parents can be maternally related through when they are pregnant. In a 2020 study, pregnant women were psychologically analyzed by filling out a questionnaire about their ACE’s and their socioeconomic statuses. Not only did the women with the highest ACE’s have shortened telomeres but their infants did as well (Esteves et al., 2020). This shows that early life stress and its effects on telomere length are not limited to the lifetime of the child but also their time in the womb. This puts an importance in looking at the mothers experiences and stress levels to predict the mental and physical well beings of their children.
In addition, stress alone did not prove to cause shortened telomere lengths, there were also other factors, one of which being gender. One study done in 2018 by Xavier et al., looked at child maltreatment, which the World Health Organization defines as all forms of physical or emotional ill-treatment, sexual abuse, neglect, and negligent treatment that can stunt or threaten the safety and development as a child. They found that specifically males with higher child maltreatment exhibited shortened telomere length. They also determined that premature aging and psychiatric disorders, due to the shortening of telomeres caused by childhood stress, was more common in adult males (Xavier et al., 2018). This influence of sex on telomere length may potentially be due to discrepancies in hormonal processes, as it is known that estrogen is capable of activating telomerase. This means that the estrogen present in women protects their telomeres from erosion. On the other hand, testosterone has been known to increase the susceptibility to oxidative stress which could potentially expedite the shortening of telomeres, thus it makes sense that males seem to be more affected (in terms of telomere shortening) by life adversity (Xavier et al., 2018).
In addition, in the aforementioned study done on the effects of father loss by Mitchell et al., in 2017, the results similarly found a discrepancy within sexes; the effects were 40% greater in boys (Mitchell et al., 2017).
Though these deductions are rational, there are not many studies done on this topic and more research should be done to confirm that there is a correlation between sex and the effects of life stress on telomere length.
There were also studies on the relationship between telomere length and the risk for psychiatric disorders. A study done in 2018 by Palmos et al., did not find that there was any link between shortened telomere length, however it did find that antidepressants used for psychiatric disorders did affect telomere length. The study demonstrated that antidepressant use was significantly linked to shorter telomere length, independent of depression diagnosis (Palmos et al., 2018). Another study, however, found that children who had a history of early institutionalized care from severe psychological issues showed significantly shortened telomere length in contrast to children who were never institutionalized (Humpries et al., 2018). This shows that there have been varied results in whether or not shortened telomere length is caused by or causes mental health issues and psychopathology, and more research should be done.
Significance of Shortened Telomere Length
By now one can understand that there is enough evidence to support that early life adversity has a role in telomere shortening. This in turn shows that early life adversity is directly correlated to many negative outcomes later in life. There is one obvious deduction that can be taken away from this, and that is that telomere length can be used as a biological marker for predicting health outcomes and determining the stress levels of children. By using telomere length and early life adversity as a marker we can predict a child’s long term-health and overall well being, as well as their susceptibility to diseases and premature mortality. Not only can telomere shortening be used to determine physical ssues such as cardiovascular diseases, but it can also be used as a psychological biomarker (Coimbra et al., 2017).. Children with shorter telomeres have been found to have more psychiatric issues such as bipolar disorder, schizophrenia, major depression, and post trauma stress disorder (Coimbra et al., 2017). Another study supported these findings, as it also determined that in children ages 8 to 10 shorter telomere length was associated with internalizing psychopathology issues which includes anxiety, depression and phobias. The study also found that in children ages 12 to 14, shorter telomeres were associated with higher general psychopathology. This study concluded by stating that telomere erosion could be due to distress related psychopathology instead of what causes it later in life (Wade et al., 2020).
Conclusion
As mentioned, not only was early life stress shown to be more consequential in telomere length than later life stress, but there is a large amount of evidence that confirms that the acceleration of telomere shortening is evident in children shortly after they are exposed to trauma and adversity. By using this knowledge, as well as by using stress levels and telomere length as a biomarker, we can predict which children are going to be affected in the long term. Since early life adversity has such an impact, it is important to prevent early life stress as much as possible. As a population we have a responsibility to try to prevent as much damage to the health of future generations, and the best way this can be done is by trying to avert as much adversity as possible during childhood. This concept that early life adversity can cause detrimental long term effects in children should be advertised and become common knowledge throughout the world. In an ideal society it would hopefully make people think twice about what they say or do around a child if they know that their actions can have consequences that follow the child for the rest of their lives.
Caregivers, community members, and mental health professionals have a fundamental role and a responsibility in nurturing children and preventing stress to ensure their health for the rest of their life. This puts the importance of parental responsiveness in moderating early-life stress in children into perspective.This can be done by caregivers attending to the child’s needs in a timely manner and to diffuse and avoid stressful and traumatic situations for the child. In addition, the importance of financial and emotional stability should be stressed to couples who are considering having children as socioeconomic status proved to be one of the most influential types of adversity on the shortening of telomeres.
In addition to that, as previously mentioned, sometimes parents prove to be the issue and the cause for stress in children, whether that is through physical, emotional, sexual abuse or any other form of maltreatment. Due to that, schools should have a greater role in evaluating the stress levels of children through psychological checkups without their parents present.
This can ensure that the parents are not causing psychological and physical long term damage to their children. This is not limited to the actual life of children, telomere length and stress should also be evaluated and used as markers in mothers. Wide-spread screening should be done on women who are pregnant to look at potential stressors during pregnancy and to prevent any type of acceleration of telomere shortening in the offspring. This can be done as a preventative measure to reduce as much mental and physical complications later in life. In addition, it should become a common fact that women should also try to avoid putting themselves in any sort of stressful situation. A potential way to decrease maternal stress is through the normalization of paid paternal and maternal leave. This will limit the amount of stress that women have whether it is physical, work, or financially related. There are several countries in the world who already have this institution in place such as Canada, Israel, Slovakia, Switzerland, and Costa Rica. A potential way to determine if this would be a good idea would be to do a study to see how the telomere lengths of people who live in countries with paid parental leave (and have had it for a while) differ from those who live in countries that do not have it. Moreover, the government can also provide additional assistance to single parents as the study about paternal absence showed that there was acceleration in telomere length in children whose fathers were absent and that it was mainly due to financial reasons. By having more financial support, the stress burden on both mothers and children can be reduced.
Another aspect of life stress that was discussed was boys specifically demonstrating accelerated telomere shortening. As a whole we can normalize the importance of mental health check-ups on
males. Oftentimes males are expected to be strong and to not show weakness and this is unfortunately something that as a society has become a norm. However, by encouraging speaking about stress we can get a better psychological understanding of males life, and potentially predict and prevent any long term effects of their stress.
Various different studies have confirmed that early life stress does in fact cause a shortening of telomere length especially in contrast to later life stress which has a significantly reduced effect. This life stress includes maltreatment, abuse, low economic status, the absence of parents and much more. There has also been evidence that stress effects cause greater acceleration of telomere shortening in males than in females. There is also a link between the effects of parental caused stress on their children, specifically the absence of fathers which has been shown to cause a reduction in telomere length. Evidence also suggests that there is a link between higher maternal stress and shortened telomere length in their offspring.
By concluding that early life adversity causes telomere length, various psychological and physical diseases such as diabetes, bipolarism, schizophrenia, and many other complications that have been linked to shortened telomere length can be prevented (Esteves et al., 2020).
Life stress (including the mothers) and telomere length can serve as a marker to determine the long term health of a child. Many things can be done to potentially prevent telomere lengthening such as maternal screening and psychological checkups on children. Though there seems to be a copious amount of information something discovered within the research of the effects of early life stress on telomere length is that there are very few longitudinal studies, thus it is integral to the health of future generations that more research is done, and more initiative is taken in trying to reduce early life adversity.
References
1.Coimbra, B. M., Carvalho, C. M., Moretti, P. N., Mello, M. F., & Belangero, S. I. (2017). . Journal of Psychiatric Research, 92(1), Stress-related telomere length in children: A systematic review 47–54.
2. Esteves, K. C., Jones, C. W., Wade, M., Callerame, K., Smith, A. K., Theall, K. P., & Drury, S. S. (2020). Adverse Childhood Experiences: Implications for Offspring Telomere Length and Psychopathology. The American Journal of Psychiatry, 177(1), 47–57.
3. Gerritsen, L., Hagg, S., Reynolds, C., & Pedersen, N. (2019). Early and late-life stress and longitudinal telomere length in old twins. European Neuropsychopharmacology, 29(1, Number 1 Supplement 1), S218.
Humphreys, K. L., Esteves, K., Zeanah, C. H., Fox, N. A., Nelson, C. A., & Drury, S. S. (2016). Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level. Psychiatry Research, 246(1), 95–100.
5. Mitchell, C., McLanahan, S., Schneper, L., Garfinkel, I., Brooks-Gunn, J., & Notterman, D. (2017). Father Loss and Child Telomere Length. Pediatrics, 140(2), e20163245.
6. Palmos AB, Breen G, Goodwin L, Frissa S, Hatch SL, Hotopf M, Thuret S, Lewis CM and Powell TR (2018) Genetic Risk for Psychiatric Disorders and Telomere Length. Front. Genet. 9:468. doi: 10.3389/fgene.2018.00468
7. Wade, M., Fox, N. A., Zeanah, C. H., Nelson, C. A., & Drury, S. S. (2020). Telomere Length and Psychopathology: Specificity and Direction of Effects Within the Bucharest Early Intervention Project. Journal of the American Academy of Child & Adolescent Psychiatry, 59(1), 140–148.e3.
8. Xavier, G., Spindola, L. M., Ota, V. K., Carvalho, C. M., Maurya, P. K., Tempaku, P. F., Moretti, P. N., Mazotti, D. R., Sato, J. R., Brietzke, E., Miguel, E. C., Grassi-Oliveira, R., Mari, J., Bressan, R. A., Gadelha, A., Pan, P. M., & Belangero, S. I. (2018). Effect of male-specific childhood trauma on telomere length. Journal of Psychiatric Research, 107(1), 104–109.
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