Short telomeres confer risk of degenerative diseases. Chronic psychological stress can lead to disease through many pathways, and research from in vitro studies to human longitudinal studies has pointed to stress-induced telomere damage as an important pathway. However, there has not been a comprehensive model to describe how changes in stress physiology and neuroendocrine pathways can lead to changes in telomere biology. Critically short telomeres or the collapse of the telomere structure caused by displacement of telomere binding protein complex shelterin elicit a DNA damage response and lead to senescence or apoptosis. In this narrative review, we summarize the key roles glucocorticoids, reactive oxygen species (ROS) and mitochondria, and inflammation play in mediating the relationship between psychological stress and telomere maintenance. We emphasis that these mediators are interconnected and reinforce each other in positive feedback loops. Telomere length has not been studied across the lifespan yet, but the initial setting point at birth appears to be the most influential point, as it sets the lifetime trajectory, and is influenced by stress. We describe two types of intergenerational stress effects on telomeres - prenatal stress effects on telomeres during fetal development, and 'telotype transmission" -the directly inherited transmission of short telomeres from parental germline. It is clear that the initial simplistic view of telomere length as a mitotic clock has evolved into a far more complex picture of both transgenerational telomere influences, and of interconnected molecular and cellular pathways and networks, as hallmarks of aging where telomere maintenance is a key player interacting with mitochondria. Further mechanistic investigations testing this comprehensive model of stress mediators shaping telomere biology and the telomere-mitochondrial nexus will lead to better understanding from cell to human lifespan aging, and could lead to anti-aging interventions.

OBJECTIVE: Several studies have found associations between a diagnosis or symptoms of major depressive disorder and markers of cellular aging and dysfunction. These investigations, however, are predominantly cross-sectional and focus on adults. In the present study, we used a prospective longitudinal design to test the cross-sectional association between depressive symptoms in adolescents and telomere length (TL) as well as mitochondrial DNA copy number (mtDNA-cn). METHOD: A total of 121 adolescents (mean age = 11.38 years, SD = 1.03; 39% male adolescents and 61% female adolescents) were followed for approximately 2 years. At baseline and follow-up, participants provided saliva for DNA extraction, from which measures of TL and mtDNA-cn were obtained. Depressive symptoms were obtained via the Childrens Depression Inventory. RESULTS: There was no association between depressive symptoms and markers of cellular aging at baseline; however, depressive symptoms at baseline predicted higher rates of telomere erosion (β = -0.201, p = .016) and greater increases in mtDNA-cn (β = 0.190, p = .012) over the follow-up period. Markers of cellular aging at baseline did not predict subsequent changes in depressive symptoms. Furthermore, including the number of stressful life events did not alter these patterns of findings. CONCLUSION: These results indicate that depressive symptoms precede changes in cellular aging and dysfunction, rather than the reverse.

Research in the last decade has explored the length of telomeres, the protective ends of eukaryotic chromosomes, as a biomarker for the cumulative effects of environmental exposures and life experiences as well as a risk factor for major diseases. With a growing interest in telomere biology across biomedical, epidemiological and public health research, it is critical to ensure that the measurement of telomere length is performed with high precision and accuracy. Of the several major methods utilized to determine telomere length, quantitative PCR (qPCR) remains the most cost-effective and suitable method for large-scale epidemiological and population studies. However, inconsistencies in recent reports utilizing the qPCR method highlight the need for a careful methodological analysis of each step of this process. In this review, we summarize each critical step in qPCR telomere length assay, including sample type selection, sample collection, storage, processing issues and assay procedures. We provide guidance and recommendations for each step based on current knowledge. It is clear that a collaborative and rigorous effort is needed to characterize and resolve existing issues related to sample storage, both before and after DNA extraction, as well as the impact of different extraction protocols, reagents and post extraction processing across all tissue types (e.g. blood, saliva, buccal swabs, etc.) to provide the needed data upon which best practices for TL analyses can be agreed upon. Additionally, we suggest that the whole telomere research community be invited to collaborate on the development and implementation of standardized protocols for the assay itself as well as for reporting in scientific journals. The existing evidence provides substantial support for the continuation of telomere research across a range of different exposures and health outcomes. However, as with any technological or methodologic advance in science, reproducibility, reliability and rigor need to be established to ensure the highest quality research.

Background

Previous studies in adults and older children find that sugar-sweetened beverage (SSB) consumption increases risk for obesity and cellular aging, as measured by leukocyte telomere length (LTL).

Methods

In a previously described, San Francisco-based Latino birth cohort, where telomere length was measured at birth, we evaluate the relationship between beverage consumption (including SSB and 100% fruit juice), obesity, and LTL at 2-3 years old, as well as change in LTL from birth. LTL (T/S Ratio) was measured in 61 children (mean 2.4 years ±0.6 standard deviation). Multivariable linear regression models are used to ascertain beverage type and obesity as independent predictors of LTL and change in LTL.

Results

Mean telomere length was 1.58 ± 0.20 (T/S Ratio) and mean yearly change was -0.08 ± -0.09 (T/S Ratio). Predictors of shorter telomere length at age 2-3 included increased consumption of SSB (Beta Coeff = -0.009 95% CI [-0.02 to -0.0008]; p = 0.03). Telomere length at birth was the strongest predictor of rate of attrition from birth to 2-3 years of age and males tended to have more rapid attrition.

Conclusion

Excessive SSB consumption impacts early childhood immune system health adversely, possibly before the development of obesity.

OBJECTIVE: Family members are typically the primary caregivers of patients with chronic illnesses. Family caregivers of adult relatives with cancer are a fast-growing population, yet the physical consequences of their stress due to the cancer in the family have been poorly understood. This study examined the bidirectional relations of the perceived stress of family caregivers of individuals recently diagnosed with cancer and leukocyte cellular aging indexed by telomere length for 2 years. METHODS: Family caregivers ( N = 168; mean age = 51 years, 70% female, 46% Hispanic, 36% spouse to the patient) of patients with colorectal cancer provided psychological data and peripheral blood samples approximately 4 (T1), 12 (T2), and 21 months (T3) after diagnosis. Time-lagged cross-panel modeling was used to test the associations of perceived cancer-related stress and telomere length, controlling for age, sex, and body mass index. RESULTS: Cancer-related stress was highest at T1 and decreased by 1 year. Greater cancer-related stress predicted longer telomere length at subsequent assessments for 2 years ( β ≥ 0.911, p ≤ .019). However, telomere length did not change significantly for 2 years overall and did not prospectively predict cancer-related stress over this period. CONCLUSIONS: Findings suggest the need to better understand how the perceived stress of colorectal cancer caregivers, which tends to be intense for a relatively short period compared with dementia caregiving, may impact immune cell distributions and telomere length. These findings emphasize the need for further knowledge about psychobiological mechanisms of how cancer caregiving may impact cellular aging.

PURPOSE: We sought to assess the association of reports of discrimination with leukocyte telomere length (LTL) and effect measure modification by social support. METHODS: This study used data from the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (n = 1153). Discrimination was measured using the everyday discrimination and the major experiences of discrimination scales. LTL was defined as the ratio of telomeric DNA to single-copy control gene (mean = 0.916, SD = 0.205). Linear regression models were used to examine the relationship between discrimination and LTL. RESULTS: We found no association between either measure of discrimination and LTL, but there was evidence of effect modification by social support (P (χ2) = 0.001) for everyday discrimination only. Among those with low social support, reporting moderate and high everyday discrimination was associated with a 0.35 (95% CI: -0.54 to -0.16) and a 0.17 (95% CI: -0.34 to -0.01) shorter telomere length, respectively, compared to reporting no discrimination, after adjusting for demographic factors, health behaviors, and health conditions. There were no associations between discrimination and LTL among those reporting moderate or high social support. CONCLUSIONS: These findings underscore the importance of continued investigation of the potential health consequences of chronic unfair treatment in the absence of supportive resources.

Aims

Shorter telomere length is associated with increased chronic disease risk in adulthood including diabetes mellitus and cardiovascular risk. Few studies have evaluated the relationship between telomere length change and incident disease risk in populations with a high percentage of overweight and obesity.

Results

In an urban Latina population recruited in San Francisco (n = 82) with a high prevalence of overweight and obesity (78.4%), we assessed leukocyte telomere length and telomere length change over a 1-year period in relation to obesity, chronicity of obesity, and incident metabolic disease risk 5-6 years later. We also assessed the relationship between telomere length change over a 1-year period and weight loss. There were no significant associations between baseline telomere length and socio-demographics including age and ethnicity, or current weight status. Telomere length change, however, was associated with being obese at baseline and previous years of chronic obesity. A high percentage of women who were obese at baseline were also obese the year before (90%) and 2 years before (85%). Obesity at baseline was an independent predictor for increased telomere length attrition (β = -346.9, -568.4 to -125.4; P < 0.01). Similarly, chronic obesity was associated with increased risk for accelerated attrition (β = -280.6, -518.4 to -42.8; P < 0.01).

Innovation

We speculate that accelerated attrition may be a harbinger of metabolic disease. We also found that those who had or developed hypertension had accelerated attrition [-407.4 ± 464.0 vs. -168.1 ± 643.6 (P = 0.03)].

Conclusion

In populations with chronic and long-standing obesity, telomere length attrition rate, rather than baseline telomere length may be a more sensitive indicator of health status including chronic disease development.

Background

Telomere length (TL) is a marker of cellular aging, with the majority of lifetime attrition occurring during the first 4 y. Little is known about risk factors for telomere shortening in childhood.

Objective

We evaluated the relation between early life feeding variables and preschool TL.

Design

We assessed the relation between dietary, feeding, and weight-associated risk factors measured from birth and TL from blood samples taken at 4 y of age (n = 108) and 5 y of age (n = 92) in a cohort of urban, Latino children (n = 121 individual children). Feeding variables were evaluated in children with repeat measurements (n = 77).

Results

Mean TL (in bp) was associated with exclusive breastfeeding at 4-6 wk of age (adjusted coefficient: 353.85; 95% CI: 72.81, 634.89; P = 0.01), maternal TL (adjusted coefficient: 0.32; 95% CI: 0.11, 0.54; P < 0.01), and older paternal age (adjusted coefficient: 33.27; 95% CI: 4.10, 62.44; P = 0.03). The introduction of other foods or drinks in addition to breast-milk or replacement-milk substitutes before 4-6 wk of age was associated with mean TL at 4 and 5 y of age (adjusted coefficient: -457.01; 95% CI: -720.50, -193.51; P < 0.01). Infant obesity at 6 mo of age and soda consumption at 4 y of age mediated the relation in part between exclusive breastfeeding at 4-6 wk of age and mean TL at 4 and 5 y of age. High soda consumption at 3 y of age was associated with an accelerated attrition from 4 to 5 y of age (adjusted coefficient: -515.14; 95% CI: -986.06, -41.22; P = 0.03).

Conclusion

Exclusive breastfeeding at 4-6 wk of age may have long-term effects on child health as evidenced by longer TL at 4 and 5 y of age.

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva. Methods: TL was measured in 24 healthy young adults using three modes of sample collection for each participant: venous whole blood, finger prick dried blood spot and saliva. Relative TL was measured using quantitative polymerase chain reaction. Results: TL in finger prick dried blood spots (DBS) washighly correlated with TL in whole blood (r = 0.84, p < 0.001). Salivary TL was also correlated with whole blood TL (r = 0.56, p = 0.005), but this association was not as strong as that of dried blood spot TL (Steigers Z = 2.12, p = 0.034). TL was longer in saliva than in whole blood or DBS (ps < 0.001). Conclusions: These findings have important implications for future study design by supporting the validity of less-invasive methods that can be implemented with vulnerable populations or in the field. Further, these findings aid in interpreting the burgeoning area of biological aging research and may shed light on our understanding of inconsistencies in the empirical literature.