Causes of telomere shortening and effects on aging

Many studies highlight the fact that telomere shortening is a phenomenon associated with age [1] [2]. However, the speed of shortening can vary from one individual to another, although this has not yet been fully clarified. Throughout this article, we will then focus on the numerous causes that could explain differences in telomere length from one individual to another.

Causes of accelerated telomere shortening leading to aging

Many factors accelerate telomere shortening and aging

Rates of telomere shortening are different between men and women [3]. Indeed, a study demonstrated that in a group of 48-year-old men and women, there was a significant difference in telomere length of approximately 320 bp [3]. Telomere shortening appears to be faster in men than in women. Telomere length being associated with biological age and aging (see:  Telomeres: at the heart of the aging process ), this difference in speed of shortening could be a factor explaining why life expectancy is on average greater in women than in men.

There are also external factors that can accentuate telomere shortening. We find, for example, tobacco, stress or even socio-professional conditions [4]. Factors relating to poor health such as obesity, inflammatory conditions or cardiovascular diseases [4] also come into play.

Other factors come directly from our genome, so that it seems to be programmed to cause the organism to age. For example, telomeric DNA has a high proportion of guanine in its sequence. However, guanine has a high risk of oxidation into “8 — oxo-guanine”, a compound causing numerous dysfunctions in the genome and difficult to repair [4]. The very composition of the telomere could then make its conservation over time difficult.

All of these factors can accelerate telomere shortening and accelerate aging.

Stress accelerates aging by shortening telomeres

A state of psychological stress at work occurs when there is an imbalance between a person's perception of the constraints imposed on them by their working conditions and their perception of their own resources to cope with them. If stress is not an illness, prolonged exposure to stress can be harmful to health, we then speak of chronic stress [5].

Numerous studies have demonstrated that there is a link between chronic stress at work and deterioration in health, through an increase in the risk of developing cardiovascular diseases and a weakening of the immune system [6]. Although the mechanism linking stress to health and aging has not yet been fully elucidated, we know that it causes disruptions in cellular functioning. However, the cellular environment plays an important role in the regulation of telomere length and telomerase activity. Researchers conducted a study in healthy women experiencing varying levels of chronic stress, to determine whether this had an impact on telomere length and an influence on physiological age [6].

It was observed that individuals experiencing greater stress had shorter telomeres. On average, there is a difference of 550 bp in the telomeric sequence, independent of age, between individuals experiencing high stress and those experiencing low stress at work [6]. This difference is associated with an increase of approximately 10 years in biological age [6].

Concerning telomerase activity in the group experiencing high stress, it was 48% lower compared to individuals experiencing lower stress. When this decline in telomerase activity becomes chronic, it also contributes to the accelerated shortening of telomeres [6].

Telomere shortening has therefore been shown to be influenced by extracellular factors, such as psychological stress at work. The latter would be strongly linked to the increase in oxidative stress, a decrease in telomerase activity and an accelerated shortening of telomeres. All these factors would result in the premature entry of cells into senescence [6], with a direct impact on the lifespan of cells and on physiological age.

Smoking and being overweight accelerate telomere shortening and aging

Being overweight and smoking are two factors that could increase the risk of developing age-related diseases. Indeed, in addition to having harmful consequences on health such as increased inflammation or the development of oxidative stress, it seems that these two factors are also able to accentuate the degradation of telomeres [7 ]. But what about their influence on physiological aging?

Effects of these two factors on telomere shortening and biological aging

Comparative studies of telomere length have been conducted in adult women between 18 and 76 years of age. It was first observed that the length of telomeres decreases regularly with age: approximately 27 bp per year [7].

However, in overweight women, telomeres were 240bp shorter compared to women with “normal” build. This difference in telomere length would correspond to an increase of 8.8 years in physiological age [7].

Concerning cigarettes, a dependence relationship with the dose consumed was observed. For the group of smokers, each year there is an additional loss of 5bp of telomeric DNA, or 18% more loss, than in a non-smoking individual. This was associated with 4.6 years of extra biological age for smokers and 7.4 years more for those who smoked 1 pack per day for 40 years or more [7].

This study is representative of the great diversity in the speed of telomere shortening between individuals. These two health risk factors, tobacco and obesity, then seem to have a direct influence on life expectancy.

Different rates of telomere shortening and aging depending on SES

Socioeconomic status (SES) determines the position an individual occupies in society, relating to the combination of several social and economic factors. Numerous studies have demonstrated that in people with a low SES level, there is a greater risk of developing cardiovascular, respiratory, joint and psychological diseases [8]. Unfavorable socio-economic conditions could then lead to a reduction in life expectancy.

Researchers used telomere length as a biological indicator of aging to test the link with SES. The study was carried out on the white blood cells of 1552 female twins, whose telomere length was measured. At the same time, a questionnaire about the participants' lifestyle was distributed concerning: profession, level of education, income, smoking, sporting activity, height and weight.

The origin of the link between SES and aging accelerated by telomere shortening

The hypothesis that this difference could be due to poverty or lack has not been proven. Indeed, there is no proven link between income level and telomere length [9]. However, another hypothesis could explain these disparities: that of the lack of access to information concerning health risks, despite the fact that there is no significant correlation between the level of education and telomere length [9], when all other parameters are equal. The origin of these differences in telomere length between the different SES levels therefore still remains to be determined.

However, this study highlighted the fact that unfavorable socio-economic conditions accentuate the influence of external factors such as tobacco, obesity and lack of exercise on the shortening of telomeres.

Thus, there are many factors that can influence telomere length [8]. One might think that it would be possible to increase life expectancy by acting directly on these different factors, even if the mechanisms explaining the link with aging physiology are not yet fully elucidated.

SOURCES:

Katidja Allaoui on http://www.longlonglife.org/

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[2] Shay, J. (2016). Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discovery, [online] 6(6), pp.584-593. DOI: 10.1016/j.semcancer.2011.10.001 [Accessed 22 May 2017].

[3] Wolkowitz, OM, Jeste, DV, Martin, AS, Lin, J., Daly, RE, Reuter, C., & Kraemer, H. (2017). Leukocyte telomere length: Effects of schizophrenia, age, and gender. Journal of psychiatric research , 85 , 42-48.

[4] Blasco, M.A. (2007). Telomere length, stem cells and aging. Nature chemical biology, 3(10), 640-649.

[5] http://www.journal-officiel.gouv.fr/publications/bocc/pdf/2009/0019/CCO_20090019_0019_0041.pdf

[6] Epel, ES, Blackburn, EH, Lin, J., Dhabhar, FS, Adler, NE, Morrow, JD, & Cawthon, RM (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences of the United States of America, 101(49), 17312-17315.

[7] Valdes, AM et al. Obesity, cigarette smoking, and telomere length in women. Lancet 366, 662–664 (2005).

[8] Balia, S., & Jones, A.M. (2008). Mortality, lifestyle and socio-economic status. Journal of health economics, 27(1), 1-26.

[9] Cherkas, LF, Aviv, A., Valdes, AM, Hunkin, JL, Gardner, JP, Surdulescu, GL, … & Spector, TD (2006). The effects of social status on biological aging as measured by white‐blood‐cell telomere length. Aging cell, 5(5), 361-365.