Lifestyle effects on telomeric shortening as a factor associated with biological aging: A systematic review

4.1Physical activity

Regular physical activity has been shown to have a positive effect on telomere length. Moderate levels of physical activity have been studied extensively and are most closely related to longer telomere lengths independent of other possible confounding factors such as: Body Mass Index, diseases, and demographic characteristics, among others [16, 17]. In a study conducted by Du et al. [5], older women (average age of 59 years old) who had moderate or high physical activity showed a significantly longer leukocyte telomere length (LTL) than less active women. For this study, this difference in telomere length is calculated as an average of 4.4 years of aging among participating women. In another study, Tucker [18] found that participants in NHANES (National Health and Nutrition Examination Survey) with high physical activity had significantly longer telomeres. On average, the participants’ telomeres were 140 bp (base pairs) longer than sedentary people, which is equ-ivalent to being an average of 9 years younger [18].

In addition to moderate or vigorous physical activity, higher intensity exercise levels also showed a positive correlation to telomere length. This may include resistance training, triathlon training at a competitive level, or almost any sport at a professional or elite level. The positive impact of this level of exercise is mainly due to the physiological processes activated by these levels of physical activity. Colon, et al. [19] found greater telomere lengths in competitive level triathletes in comparison to recreationally active people. This demonstrates a positive relationship between telomere length and athlete development parameters, such as VO2max or greater aerobic capacity in triathletes. The previous allows for greater performance, as well as reliance on oxidative metabolism pathways. These characteristics are part of the same phenotype as longer telomere lengths [19]. The relationship between telomere length and high intensity exercises is mainly due to the capacity of redox balance (oxidation-reduction) caused by the effects of this level of exercise on the body [20]. For example, resistance training has been shown to generate a higher availability of nitric oxide (NO) and an increase in the activity of SOD (superoxide dismutase enzyme), indicating a greater regulation of the levels of nitrogen free radicals (produced by the reaction NO with O2) and ROS, which is associated with an improvement in the oxidative response and a reduction in oxidative stress markers [20]. Likewise, an adaptation of specific antioxidants/oxidative stress markers, an improvement in the maintenance of LTL and a reduction in DNA methylation levels has been observed in resistance training practitioners, indicating a greater antioxidant capacity in the cell. which can provide better telomere maintenance and prevent DNA damage from oxidative stress [14]. Taking into account these effects on redox homeostasis and telomere length, maintaining regular physical activity at a moderate to intense level can be considered as a factor that helps reduce telomeric shortening, improving the oxidative response, thus contributing to prevent accelerated aging.

4.2Diet

Diet has shown to have different effects on telomere length depending primarily on the type of food consumed. Foods with unhealthy characteristics have been linked to shorter telomeres. In a study conducted by Fretts, et al. [9], American Indians of the Strong Heart Family tested the relationship between the consumption of processed and unprocessed red meat with LTL. They found that the consumption of processed red meat is related to shorter LTL. For each serving of meat consumed, telomere length shortened by approximately 4 years; however, no relationship was found regarding the consumption of unprocessed red meat [9]. Telomere shortening due to the consumption of processed red meat may be linked to high protein, fat, and AGE (Advanced Glycation End-products) contained within the meat. These substances cause oxidative stress and trigger an inflammatory response, which promotes the oxidation of DNA and the accelerated shortening of telomeres [9, 21].

Healthy foods and supplements have been shown to have a positive effect on telomere length. Tucker [22], for example, investigated the relationship between dietary fiber consumption (self-reported) and leukocyte telomere length (LTL) in participants of the NHANES study (National Health and Nutrition Examination Survey, USA). They found that a higher consumption of dietary fiber results in longer telomeres. For every 10g of fiber (per 1000 kcal) consumed, telomeres were 67 base pairs longer equivalent to 4.3 years less of aging [22]. Another study by Nonino, et al. [23] found a positive relationship between telomere length and drinking green tea in obese women. After an 8-week period of drinking green tea, obese women showed a significant increase in telomere length compared to telomere length before the intervention; effect that can be explained due to the antioxidant components present in green tea, such as flavonoids and mainly epigallocatechin-3-gallate (EGCG) [23].

Some nutrients have also been shown to increase telomere length, notably omega-3 fatty acids, vitamins, and minerals. This is due to their antioxidant capability (Omega 3, Vitamins C and E), oxidative stress control, inflammatory and immune response (Vitamins D, A, and B12), or DNA damage response action (Folate and Nicotinamide) which can control telomere length and aging [21, 24].

Diets rich in fruits and vegetables, such as the Mediterranean diet, have also been shown to have a positive effect on telomere length, thereby, decreasing the aging process [25, 26]. A study conducted by Gong et al. [27] found among 4 dietary patterns that only the ‘rich in vegetables’ pattern that was characterized by a major intake of fruits, whole grains, various groups of vegetables, dairy products, nuts, eggs and tea, was positively related to TL in women, while the other patterns did not show a statistical relationship with TL [27]. This positive effect of the dietary pattern on LT is largely due to the antioxidant capacity of these foods, which contributes to the reduction of oxidative stress, which has been related to the maintenance of telomeres [28]. In this way, it is advisable to increase the consumption of fruits and vegetables and other foods with antioxidant potential, in order to help regulate the length of telomeres, improve the response of cells to oxidative stress, and reduce damage to DNA that causes aging.

4.3Techniques for the control of psychological stress

Controlling psychological stress has been shown to have a positive effect on the maintenance of telomeres. Different techniques to control stress have shown an effect on reducing the length of telomeres over time, as well as improving complications from disease and age. Duan, et al. [29] found that Tai Chi has been related to increased telomerase activity in peripheral blood mononuclear cells after 6 months in middle-aged adults (55–65 years). This increase in telomerase activity may act as a contributing factor to the maintenance of telomeres [29]. Krishna, et al. [30] compared healthy and active yoga practitioners (30–40 years) to healthy non-yoga practitioners and found that regular practitioners of yoga had longer telomere lengths, a reduction in systemic oxidative stress markers (total antioxidant status), and lower Malondialdehyde and homocysteine levels [30].

Meditation and other techniques have been shown to maintain the length of telomeres and control the factors involved in their shortening. A follow-up study conducted by Ornish, et al. [13] found that a comprehensive 5-year lifestyle intervention, which included meditation, was associated with longer telo-meres, and an increase (at 3 months of intervention) and subsequent reduction (at 5 years of intervention) in telomerase activity among men diagnosed with low-risk prostate cancer through an active surveillance (biopsy). Dada, et al. [31] and Tolahunase, et al. [32] found that meditation during yoga practice resulted in longer telomeres, a reduction in oxidative stress markers, and lower DNA damage in sperm cells [13, 31, 32]. Meditation techniques alone have also demonstrated an effect on telomere length. Hoge, et al. [33] conducted a study on people (ages 18 or older) practicing Metta Meditation or love-kindness (which focuses on positive intention, kindness, and human warmth) in comparison to non-practitioners of yoga or meditation. They found a significantly higher leukocyte telomere length only in the women practicing this meditation technique [33]. In another study conducted by Conklin, et al. [34], the participants engaged in a month of Insight Meditation (a vipassana practice, based on meditative withdrawal and focus on deep and isolated concentration) showed an average increase in telomeric length of 104.2 bp in peripheral blood mononuclear cells (equivalent to a 4-year decrease in aging), in addition to presenting slightly higher patterns of telomerase activity and gene expression related to telomere biology, (mainly Atrip, Cct1, Cct6, Gar1 and Hnrnpa1) in meditating practitioners after 3-weeks of Insight meditative withdrawal [34].

The capability of these practices on telomere mai-ntenance is mainly linked to both physical and psychological qualities. Since these practices are mind-body interventions, they have moderate to intense levels and utilize various breathing techniques that contribute to the improvement of conditions related to lifestyle (Body Mass Index and glucose levels), inflammatory response, and the reduction of oxidative stress levels in the body. Therefore, cell damage is decreased, and telomere maintenance mechanism are activated. This contributes to the cell’s longevity and improves the health of the cell at the somatic and reproductive level. The appearance of aging in relation to diseases like cancer is reduced both at and early and future age [29–34]. Different stress management techniques have an important role in both psychological and physical health, which also contribute to the regulation of oxidative stress levels and telomere shortening. Thus, it is advisable to regularly practice these techniques and reduce the effects of psy-chological stress as a means to slow down one’s aging.

5.1Smoking and alcoholism

Although cigarette and alcohol consumption have been linked to other diseases (including cancer), their effect on telomere length is still unclear. While some studies generally report these factors as being negatively related to telomeric length, other studies report an insignificant or null relationship. For example, Latifovic et al. [35] conducted a cross-sectional study among men and women (20–50 years) to determine the influence of alcohol, cigarette consumption, and physical activity (self-reported) on the relative Length of Leukocyte Telomere (rLTL) measured by quantitative PCR. The findings showed that daily cigarette consumption was related to shorter rLTL (on average 0.096 relative units shorter than in non-smokers). However, they found no relationship between alcohol consumption (self-reported as moderate by the participants) and telomere length compared to other research studies [35]. Likewise, Muezzinler, et al. [36] studied a subsample of men and women (50–75 years) from the ESTHER study (Epidemiological Study on the Chances of Prevention, Early Recognition, and Optimized Treatment of Chronic Diseases in the Older Population). They found an inverse relationship between smoking and LTL, where current smokers had shorter telomeres than non-smokers. In addition, the intensity of the habit was related to lower LTL, but they found that smoking was associated with lower rates of telomere shortening during the 8-year follow-up. As a secondary result, shorter telomeres were found in association to increased alcohol consumption [36].

Although alcohol consumption is a major risk factor for morbidity and mortality, its link to telomere length is still unknown. Some studies have shown telomere shortening when alcohol consumption is increased, while others have reported beneficial health benefits with moderate consumption [24]. In the case of smoking, the intensity of consumption has been linked to telomere shortening [37]. Revesz et al. [38] found that smoking was associated with shorter telomeres, along with other factors. Huzen, et al. [39] found smoking as a factor related to telomeric length change, where active smokers had an annual shortening rate of three times over non-smokers. Moreover, people who quit smoking had an annual telomere shortening rate comparable to people who had never smoked. The negative effect of smoking on telomere length may be due to the free radicals it produces, which induce oxidative stress. This results in an accelerated shortening of the telomeres [37]. Even though the effect of these lifestyle factors on telomeric length may not be entirely clear, they can be considered as potential accelerators of telomeric shortening. Because of this, a reduction in their consumption is recommended in order to improve one’s health and slow down biological aging.

5.2Sedentary lifestyle and obesity

Sedentary behavior and obesity have also been associated with a negative effect on telomere length and aging [23, 40]. Sedentary behavior has been related to reduced mitochondrial activity (an important determinant of biological aging). It is also a predictor for conditions like obesity, which has been directly related to shorter telomeres [5, 40].

Joshu, et al. [41] conducted a study on 596 men (40–75 years) participating in the HPFS (Health Professionals Follow-up Study), who were surgically treated for prostate cancer. Prostatectomy tissue samples were measured, taking into account cell type and telomeric length. They found that the men with increased anthropometric measures (adiposity, hip circumference, and weight gain starting at 21 years of age) and lower amounts of physical activity had shorter telomeres only in stromal prostate cells. Additionally, they found that overweight or obese men, who were less active, had telomeres 20.7%shorter in stromal cells than active and normal-weight men. This ratio can be translated into a 29%increase of having fatal prostate cancer [41]. Likewise, another study conducted by Grun, et al. [42] in adults aged 18–65 discovered shorter telomeres in patients with severe or morbid obesity, as well as an increase in macromolecule oxidative damage (lipid peroxidation and protein oxidation) and antioxidant response systems non-enzymatic levels (total reactive antioxidant potential and total antioxidant reactivity). Also, they found increased levels of Shelterin complex (TRF1, TRF2, POT1 and DKC1) expression, where TRF1 levels were the main contributor to telomeric shortening in people with obesity [42]. The increase in Shelterin components expression indicated an adaptive antioxidant response insufficiency. Together with metabolic dysfunction and chronic inflammation, Shelterin components expression contributes to an increase in oxidative stress levels, accelerated telomeric shortening, and premature biological aging [23, 42]. In this way, it is crucial to control Body Mass Index, prevent obesity, and reduce sedentary habits. Therefore, accelerated aging and pathologies could be prevented early on.