Causes of telomere shortening and effects on aging

Numerous studies highlight the fact that telomere shortening is a phenomenon associated with age [1] [2]. However, the rate of shortening may vary from one individual to another, without this being fully clarified. Throughout this article, we will then look at the many causes that could explain the differences in telomere length from one individual to another.

Causes of accelerated telomere shortening leading to ageing

Many factors accelerate telomere shortening and aging

Telomere shortening rates differ between men and women [3]. Indeed, one study showed that in a group of 48-year-old men and women, there was a significant difference in telomere length of about 320 bp [3]. Telomere shortening appears to be more rapid in men than in women. Since telomere length is associated with biological age and ageing (see : Telomeres: at the heart of the ageing process), this difference in shortening speed could be a factor in the fact that life expectancy is on average greater in women than in men.

There are also external factors that may accentuate telomere shortening. These include smoking, stress and socio-professional conditions [4]. Factors related to poor health such as obesity, inflammatory conditions or cardiovascular disease [4] are also taken into account.

Other factors come directly from our genome, so that it seems to be programmed to cause the body 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 that causes many malfunctions in the genome and is difficult to repair [4]. The very composition of the telomere could then make its conservation over time difficult.

All these factors can accelerate telomere shortening and accelerate aging.

Stress accelerates aging by shortening telomeres

A state of psychological stress in the workplace occurs when there is an imbalance between a person's perception of the constraints imposed by his or her working conditions and the perception of his or her own resources for coping with them. If stress is not an illness, prolonged exposure to stress can be deleterious to one's health; this is referred to as chronic stress [5].

Numerous studies have shown that there is a link between chronic stress in the workplace and poor health, with an increased risk of developing cardiovascular disease and a weakened immune system [6]. Although the mechanism linking stress to health and ageing has not yet been fully elucidated, it is known to cause disturbances in cellular functioning. The cellular environment plays an important role in the regulation of telomere length and telomerase activity. Researchers have conducted a study in healthy women with different levels of chronic stress to determine whether this has an impact on telomere length and an influence on physiological age [6].

Individuals under greater stress were found to have shorter telomeres. On average, there is a difference of 550 bp in the telomere sequence, regardless of age, between individuals with high and low job stress [6]. This difference is associated with an increase in biological age of about 10 years [6].

Telomerase activity in the high-stress group is 48% lower than in the low-stress group. When this decrease in telomerase activity becomes chronic, it also contributes to the accelerated shortening of telomeres [6].

It has therefore been shown that telomere shortening is influenced by extracellular factors, such as psychological stress in the workplace. The latter is believed to be strongly related to increased oxidative stress, decreased telomerase activity and accelerated telomere shortening. All these factors are thought to result in premature senescence [6], with a direct impact on cell life and physiological age.

Tobacco and being overweight accelerate telomere shortening and aging.

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

Effects of these two factors on telomere shortening and biological aging

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

However, in overweight women, telomeres were 240bp shorter than in overweight women " normale ". This difference in telomere length would correspond to an 8.8 year increase in physiological age [7].

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

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

Different rates of telomere shortening and aging as a function of ESS

Socio-economic status (SES) determines an individual's position in society by referring to the combination of several social and economic factors. Numerous studies have shown that people with low SES have a higher risk of developing cardiovascular, respiratory, joint and psychological diseases [8]. 8] Adverse socio-economic conditions may then lead to reduced life expectancy.

Researchers have used telomere length as a biological indicator of aging to verify the link with SES. The study was conducted on the white blood cells of 1552 twin women, whose telomere length was measured. At the same time, a questionnaire about the lifestyle of the participants was distributed regarding: occupation, education, income, smoking, sports activity, height and weight.

The origin of the link between ESS and accelerated ageing through 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 lack of access to information about health risks, despite the fact that there is no significant correlation between education level and telomere length [9], when all other parameters are equal. The origin of these differences in telomere length between different SES levels has yet to be determined.

However, this study highlighted the fact that adverse socio-economic conditions increase the influence of external factors such as smoking, obesity and lack of exercise on telomere shortening.

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 physiological ageing are not yet fully elucidated.

SOURCES: 

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

1] Blasco, M. (2007). Telomere length, stem cells and aging. Nature Chemical Biology, [online] 3 (10), pp.640-649. DOI :10.1038/nchembio.2007.38 [Accessed 22 May 2017]

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

3] Wolkowitz, O. M., Jeste, D. V., Martin, A. S., Lin, J., Daly, R. E., 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, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (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, A.M. 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, L. F., Aviv, A., Valdes, A. M., Hunkin, J. L., Gardner, J. P., Surdulescu, G. L., & Spector, T. D. (2006). The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging cell, 5(5), 361-365.