Aging is a risk factor for several pathologies, restricting one’s health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance.
1. Introduction
Aging is defined as a diminishing of biological functions over time, in which there is a progressive loss of the function and structure of tissues and systems [
6,
18]. The underlying mechanisms of the this process have been studied in depth and it seems they are related with genetic and epigenetic alterations, proteostasis loss, telomere shortening, autophagy deterioration, and mitochondrial dysfunction, among others [
1,
4,
18,
19]. However, the specific role of each mechanism remains unknown. Furthermore, these mechanisms may be modulated by other risk factors, such as diet, tobacco smoking, physical activity (PA), stress, or sleep, which, in turn, have been associated with certain diseases related to aging [
18].
Currently, several biomarkers of biological aging have been developed. Telomeres are regions of repetitive sequences (TTAGGG)
n and associated protective proteins located at the ends of the cap-shaped linear chromosomes that preserve the integrity and stability of chromosomes during DNA replication. They are essential to chromosome stability and protect genomic DNA through various mechanisms [
20,
21,
22,
23,
24]. Usually, a relative quantification protocol by calculating the telomere/single copy gene ratio is undertaken.
The telomere is stabilized by a six-protein complex called “shelterin”, including the TRF (telomeric repeat binding factor)1, TRF2, POT1 (protection of telomeres 1), TINF2 (TERF1-interacting nuclear factor 2), RAP1 (repressor activator protein 1 and TPP1 (tripeptidyl peptidase 1) [
21,
22]. Telomeres are subject to shortening during each cell division as the DNA replication mechanism cannot copy the DNA in its entirely. The enzyme telomerase, however, can solve this problem by adding the repetitive sequences and maintaining telomere length (TL). Telomere shortening is one of the most frequently studied mechanisms in the aging process. Telomere attrition reflects the cumulative load of oxidative, inflammatory, and mechanical stress [
18,
25]. Hence, TL has been proposed as a biomarker of biological age and a risk factor for chronic diseases [
4,
18,
25,
26,
27,
28,
29,
30] and total mortality [
22,
25,
28,
29,
31,
32]. Nevertheless, the association between these outcomes and the TL marker are still under discussion due to inconsistent results [
19,
25,
33,
34,
35,
36,
37,
38,
39,
40].
One of the factors potentially contributing to the heterogeneous results is the measurement approach used to determine TL. This is an important issue given the fact that TL differs in leukocyte subtypes isolated from the same individual. Although blood leukocytes are the most commonly used samples to determine TL, it is known that TL may substantially vary across various tissue types. The terminal restriction fragment (TRF) approach is the oldest method for analyzing TL and remains the “gold standard” even in current studies. It uses the southern blot or in-gel hybridization with a specific proof for telomere DNA [
17,
18]. Other methods include the fluorescent in situ hybridization (FISH) by using digital microscopy (quantitative FISH as Q-FISH) and flow cytometry (Flow-FISH). Another method, telomere shortest length assay (TeSLA), measures the distribution of shortest telomeres in heterogeneous situations. It provides a better measurement of the shortest length of telomeres. However, the quantitative polymerase chain reaction (PCR) is most widely used for its high throughput. Despite the fast, highly sensitive nature of PCR approach, which requires low amounts of DNA, the distribution of long and short telomeres cannot be obtained, and it is not possible to evaluate TL of individual cells or chromosomes [
17,
18]. This method is often chosen for large cohort studies, using DNA from leukocytes. Additionally, telomerase activity, gene expression, or epigenetic regulation of telomere-related genes are analyzed to delve deeper on the mechanisms [
20,
21,
24].
TL is determined by the interaction between endogenous and external factors that explain greater or lesser susceptibility to accelerated aging [
22]. Therefore, the exposome could well play a fundamental role through various biological mechanisms in the maintenance of the telomeres during aging [
41,
42]. Several studies have analyzed the association between lifestyle and TL, both as a protective factor [
16,
43,
44], and as inducer of their shortening [
36,
45,
46]. Diet has been one of the most commonly studied lifestyle factors with regard to TL. Several studies have shown the benefit of consuming foods rich in antioxidants or the benefits of various diets, such as Mediterranean type diets, on telomere attrition, as witnessed in a number of the already published reviews [
47,
48,
49,
50,
51,
52].
2. Association between PA and TL
The impact of PA as a relevant factor in preventing diseases associated with aging was reported in several studies [
53,
54,
55,
56,
57,
58,
59]. However, the underlying mechanism remains to be clarified. One of the possible mechanisms could be lower telomere attrition. To date, the optimum amount of PA and the type of exercise for maintaining TL remains under debate.
An important consideration for intervention trials is the length of the intervention. Brandao et al. [95] observed that an 8-w intervention combining aerobic and strength training in sedentary women with obesity increased TL. However, it has been reported that different training modalities may exert different effects. Thus, Werner et al. [44] in a complex intervention showed that endurance and interval training increased TL, but not endurance training. In this study, telomerase activity was also measured and was positively correlated with TL. Similarly, Zietzer et al. [104] in an intervention study carried out in youth and elderly participants showed that in the youngest population, telomerase activity increased significantly in a single session of aerobic exercise [104]. When endurance athletes were compared with individuals with an average level of activity, a greater TL was observed compared with the control group.
3. Association between Telomere Length and Tobacco Smoking
Only 2 of the 21 cross-sectional studies report no association between tobacco smoking and TL [60,105]; in one additional study, the initial association between tobacco smoking and TL was non-significant after adjusting for BMI [120]. In another report [108], although smoking status was not associated with TL, there was an inverse association between the number of cigarettes smoked and TL. The initial investigation by the NHS, analyzing the association between smoking and TL in 2284 women, found no relationship between both variables [60]. Two years later, in 5862 women, that same study observed a slight association between TL and smoking, specifically 8% greater TL in subjects who had never smoked as opposed to smokers [117] The authors stated that the combined effect of various risk factors (diet, PA, weight, alcohol, and tobacco) was much greater than the individual additive effect [117]. Various authors have also found greater telomere shortening in smokers as opposed to non-smokers [119,121,122,123]. Tobacco possibly accounts for 0.64–1.23% of TL variation [116]. More specifically, there could exist 50 bp of variation between smokers and non-smokers [119], 73 bp [125], or 190 bp according to others [112].
4. Association between Telomere Length and Sleep
The influence of sleep quality and sleep disorders on aging and on physical and mental health has been recognized more recently [
138,
139]. In general, aging is associated with poor sleep. Sleep quantity and efficiency vary across the lifespan, sleep duration being shorter, and sleep efficiency being lower at older ages; these difficulties worsen after 60 years, and with some differences between men and women [
139,
140,
141]. Sex-specific differences are complex and vary by outcome [
140]. A recent review including 1.1 million people from the Netherlands, United Kingdom and United States, noted that women aged 41 years and older, despite self-reporting shorter sleep duration and lower sleep efficiency than men, had longer and more efficient sleep objectively measured by actigraphy [
142], suggesting that the studies analyzing the association between sleep and TL should consider this heterogeneity.
This entry is adapted from the peer-reviewed paper 10.3390/jcm11010076
Encyclopedia
