A systematic review on the effects of social discrimination on telomere length.

Discrimination is unfair treatment against a certain group based on race, age, gender, sexual orientation, or other social identities. Discrimination is pervasive in society, elevates psychosocial stress, and is associated with negative mental and physical health outcomes. However, more research is needed to understand the biological mechanisms underlying discrimination-related health disparities. Telomere science may contribute to elucidate some of these aspects. Telomeres are protein-DNA complexes that shorten after cell division and are valuable markers of cellular aging. Short telomeres have been associated with the onset of age-related diseases. Evidence shows that chronic psychological stress may accelerate telomere shortening. Since discrimination can lead to psychological strain with cumulative impact on general health, we hypothesized that groups that report more discrimination show reduced telomere length (TL) as a consequence of psychosocial stress elevation. Through a systematic review of the literature we found 12 articles that met our criteria. Eligible studies measured racial, gender, unfair policing, and multiple forms of discrimination in association with TL. Our review showed mixed results, suggesting that there is weak evidence of a main association between discrimination and TL. However, discrimination may interact with several variables (such as depressive symptoms, acculturation, higher socioeconomic status, internalization of negative racial bias, and not discussing discrimination experiences with others) and contribute to shorten telomeres. Discrimination is a complex social construct composed of a vast sum of experiences, impressions, and contexts that in combination with other sources of stress may have an impact on TL. Telomeres may be a plausible pathway to investigate health discrepancies in discriminated groups in society, but more evidence is needed to investigate the potential harm of discrimination on cells.

Association between telomere length and neighborhood characteristics by race and region in US midlife and older adults.

Disadvantaged neighborhoods are correlated with worse health outcomes, particularly among US Blacks. However, less is known about the link between neighborhood characteristics and biomarkers of cellular age, such as telomere length (TL), which may be implicated in racial health inequities. Moreover, this relationship may vary across US region given patterns of racial segregation across the US. Therefore, this study analyzed 2008 Health and Retirement Study data on 3,869 US-born white and Black adults >50 years old to examine race differences in the relationship between salivary TL and (1) neighborhood safety, cleanliness, and social cohesion and (2) interactions between neighborhood characteristics and US region. Neighborhood characteristics were not associated with TL in whites. However, significant associations were found among Blacks with variation by region. Blacks living in less clean neighborhoods in the Northeast (b = -0.03, SE = 0.01, p < 0.05), Midwest (b = -0.04, SE = 0.01, p < 0.01), and South (b = -0.05, SE = 0.01, p < 0.01) as well as those reporting less neighborhood safety and social cohesion in the Midwest (b = -0.03, SE = 0.02, p < 0.05 and b = -0.03, SE = 0.01, p < 0.05) and South (b = -0.03, SE = 0.01, p < 0.05 for both characteristics) had shorter TL than Blacks in the West. Therefore, exposure to neighborhood level historical discrimination and neglect may be detrimental to TL in Blacks. Future research should further examine how neighborhoods contribute to aging disparities.

Quantitative assessment of changes in cell growth, size and morphology during telomere-initiated cellular senescence in Saccharomyces cerevisiae.

Telomerase-deficient cells of the budding yeast S. cerevisiae experience progressive telomere shortening and undergo senescence in a manner similar to that seen in cultured human fibroblasts. The cells exhibit a DNA damage checkpoint-like stress response, undergo changes in size and morphology, and eventually stop dividing. In this study, a new assay is described that allowed quantitation of senescence in telomerase-deficient est2 cells with applied statistics. Use of the new technique revealed that senescence was strongly accelerated in est2 mutants that had homologous recombination genes RAD51, RAD52 or RAD54 co-inactivated, but was only modestly affected when RAD55, RAD57 or RAD59 were knocked out. Additionally, a new approach for calculating population doublings indicated that loss of growth capacity occurred after approximately 64 generations in est2 cells but only 42 generations in est2 rad52 cells. Phase contrast microscopy experiments demonstrated that senescing est2 cells became enlarged in a time-dependent manner, ultimately exhibiting a 60% increase in cell size. Progressive alterations in physical properties were also observed, including striking changes in light scattering characteristics and cellular sedimentation rates. The results described herein will facilitate future studies of genetic and environmental factors that affect telomere shortening-associated cell senescence rates using the yeast model system.

Successful aging, cognitive function, socioeconomic status, and leukocyte telomere length.

In a rapidly greying world, the notion that some individuals maintain successful aging trajectories, viz. high physical, cognitive, emotional, and social functioning in older age, is increasingly germane. Biomarkers of such successful aging are increasingly sought. Leukocyte telomere length (LTL), an emerging yardstick of cellular aging that is influenced by but distinct from chronological age, may also be associated to successful aging. Furthermore, given that socio-economic status (SES) influences successful aging trajectories, socioeconomic status may also moderate the association between chronological age and LTL. The goals of this study are to examine 1) whether successful aging is associated with LTL; 2) whether successful aging accounts for age-related LTL and 3) whether SES moderates the effect of age on LTL. Singaporean Chinese (n = 353) aged 65-80 completed a multidimensional assessment of successful aging and provided blood samples for LTL analysis. Results show that LTL negatively correlates with chronological age and positively correlates with successful aging. Successful aging mediates the association between chronological age and LTL. Moderated mediation analyses show that lower SES is associated with stronger negative associations of chronological age with successful aging and LTL. Moreover, the cognitive functioning dimension of successful aging is uniquely associated with LTL and its association with chronological age is moderated by SES. This study provides evidence that among older Singaporean Chinese with lower SES, declines in successful aging and in cognitive functioning are linked to age-related LTL shortening and hence to accelerated aging at the cellular level.

Interpersonal-level discrimination indices, sociodemographic factors, and telomere length in African-Americans and Whites.

OBJECTIVE: Studies have linked self-reported discrimination to telomere attrition, a biological marker of accelerated cellular aging. However, it is unknown whether intersections between social categories-race, socioeconomic status (SES), sex, and age-influence the association of varying forms of discrimination with telomere length. We examined these associations in a socioeconomically and racially/ethnically diverse urban sample. METHODS: Cross-sectional data were from 341 middle-aged (30-64 years) African American and White, community participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span Study (HANDLS). Multiple regression models examined up to 3-way interactions between a discrimination measure (i.e., everyday, racial, gender, lifetime burden, and frequency of discrimination across sources) and two social categories. RESULTS: After adjusting for depressive symptoms, waist circumference, and lifetime substance use, two themes emerged: 1) among women with higher SES, a) greater lifetime discrimination burden (b = -0.23, p = .011), gender discrimination (b = -0.29, p = .040), and racial discrimination (b = -0.24, p = 0.023) and 2) among younger adults, irrespective of race and sex, greater frequency of discrimination across sources (b = 0.002, p = .008) was associated with shorter telomeres. CONCLUSIONS: Irrespective of race, women with higher SES and younger adults reporting greater discrimination may be at particular risk for accelerated aging. Telomere attrition promotes and accelerates chronic health conditions for which there are health disparities. Future research explicating intersections among specific discrimination indices and social categories is warranted.

Lifetime socioeconomic status and early life microbial environments predict adult blood telomere length in the Philippines.

OBJECTIVES: Psychosocial stress is postulated to hasten senescence in part by accelerating the shortening of telomere length (TL). One pathway through which this may happen is via increasing inflammation and innate immune system activation-a pathway which recent studies suggest acts more strongly for those who grew up in low microbial environments. Thus, we hypothesized that: (1) Psychosocial stress will be inversely associated with TL, (2) early life microbial environments will predict TL, and (3) microbial environments will moderate the association between psychosocial stress and TL. METHODS: We utilized data from the Cebu Longitudinal Health and Nutrition Survey based in the Philippines (N = 1410). We determined early life microbial environments by season of birth and exposure to animal feces. Psychosocial stress measures included perceived stress in adulthood, lifetime socioeconomic status (SES), and parental instability in childhood. TL was measured in blood from young adults by qPCR. RESULTS: Contrary to predictions, we found that higher SES was associated with shorter TL and no association of TL with the other stress variables. Individuals born in the higher microbial exposure season had shorter TL, but early life microbial environments did not moderate the association between psychosocial stress and TL. CONCLUSIONS: The unexpected inverse association between SES and TL suggests that higher SES, while indexing lower psychosocial stress, may impact TL more strongly through nonstress factors in the Philippines, such as unhealthy behavior. The inverse association between microbial environments and TL is consistent with other evidence connecting early life infections to decreased life expectancies.

Justice for all? Beliefs about justice for self and others and telomere length in African Americans.

OBJECTIVE: Believing in justice can protect health. Among marginalized racial minorities however, both endorsing and rejecting beliefs about justice might be critical. The current research examined links between African Americans' beliefs about justice for self and for others and telomere length (TL)-an indicator of biological aging that is increasingly implicated in racial health disparities, with shorter telomeres indicating poorer health. METHOD: Healthy African Americans (N = 118; 30% male; M age = 31.63 years) completed individual differences measures of justice beliefs for self and others and then provided dried blood spot samples that were assayed for TL. RESULTS: We expected that a belief in justice for self would be positively associated with TL, whereas a belief in justice for others would be negatively associated. A significant 3-way interaction with chronological age confirmed this hypothesis-among older African Americans, TL was positively associated with believing in justice for self, but only when this belief was accompanied by a weak endorsement of the belief in justice for others. CONCLUSION: Findings underscore that for racial minorities, health might be best protected when justice beliefs are both endorsed and rebuffed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Childhood adversity, social support, and telomere length among perinatal women.

Adverse perinatal health outcomes are heightened among women with psychosocial risk factors, including childhood adversity and a lack of social support. Biological aging could be one pathway by which such outcomes occur. However, data examining links between psychosocial factors and indicators of biological aging among perinatal women are limited. The current study examined the associations of childhood socioeconomic status (SES), childhood trauma, and current social support with telomere length in peripheral blood mononuclear cells (PBMCs) in a sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11 weeks postpartum. Childhood SES was defined as perceived childhood social class and parental educational attainment. Measures included the Childhood Trauma Questionnaire, Center for Epidemiologic Studies-Depression Scale, Multidimensional Scale of Perceived Social Support, and average telomere length in PBMCs. Per a linear mixed model, telomere length did not change across pregnancy and postpartum visits; thus, subsequent analyses defined telomere length as the average across all available timepoints. ANCOVAs showed group differences by perceived childhood social class, maternal and paternal educational attainment, and current family social support, with lower values corresponding with shorter telomeres, after adjustment for possible confounds. No effects of childhood trauma or social support from significant others or friends on telomere length were observed. Findings demonstrate that while current SES was not related to telomeres, low childhood SES, independent of current SES, and low family social support were distinct risk factors for cellular aging in women. These data have relevance for understanding potential mechanisms by which early life deprivation of socioeconomic and relationship resources affect maternal health. In turn, this has potential significance for intergenerational transmission of telomere length. The predictive value of markers of biological versus chronological age on birth outcomes warrants investigation.

Physical Activity Domains/Recommendations and Leukocyte Telomere Length in U.S. Adults.

PURPOSE: The purpose of this study was to examine the associations between different physical activity (PA) domains, PA recommendations, and leukocyte telomere length (LTL) using data from a nationally representative sample of U.S. adults in the National Health and Nutrition Examination Survey, 1999-2002. METHODS: A total of 6933 U.S. adults (3402 men, 3531 women; age range: 20-84 yr) who completed demographic, general health and PA questionnaires and provided a blood sample were included in the analyses. Multivariable-adjusted linear regression models were used to determine associations between PA (domain-specific PA [household/yard work PA, transportation PA, moderate leisure time PA (LTPA), and vigorous LTPA], total moderate PA and PA recommendation groups), and log-transformed LTL adjusting for age, gender, education, cigarette smoking, alcohol consumption, and body mass index. RESULTS: On average, an increase of 1 h·wk of vigorous LTPA was associated with a 0.31% (P < 0.001) longer LTL, and an increase of 1 h·wk of household/yard work PA was associated with a 0.21% (P = 0.03) shorter LTL while adjusted for sociodemographic and health behavior covariates. Neither transportation PA nor moderate LTPA was significantly associated with LTL. In addition, compared with not meeting the PA recommendation (<150 min·wk), exceeding the recommended PA levels (≥300 min·wk) was positively associated with longer LTL (P = 0.04), whereas there was no difference in telomere length between those not meeting versus those meeting the PA recommendation (150-299 min·wk). CONCLUSION: Greater engagement in vigorous LTPA and exceeding the PA recommendation may have a protective effect against telomere shortening. Future studies should examine the association between PA and LTL by exploring potential mediators such as sedentary behavior, genetics, nutrition, and chronic diseases.

Mean telomere length is not associated with current health status in a 50-year-old population sample.

OBJECTIVES: Telomeres are nucleoprotein complexes that cap the ends of linear chromosomes. Telomeric DNA decreases with age and shows considerable heterogeneity in the wider population. There is interest in the application of telomere length measures as a biomarker of general health or "biological age," and the possibility of using mean telomere length to gauge individual disease risk, and to promote lifestyle changes to improve health. This study examined the effectiveness of telomere length as a biomarker for an individual's current overall health status by assessing several measures of general health including SF-36v2 score, current smoking status and a comprehensive obesity phenotype. METHODS: Participants were from the Canterbury Health, Ageing and Lifecourse (CHALICE) cohort, a New Zealand population based multidisciplinary study of aging. Telomere length measurements were obtained on DNA from peripheral blood samples at age 49-51 (n = 351), using a quantitative polymerase chain reaction assay. RESULTS: No associations were found between telomere length measured at age 49-51 and any measures of current health status. The only significant association observed was between telomere length and gender, with females having longer telomere length than men. CONCLUSIONS: Our results suggest that telomere length measurements are unlikely to provide information of much predictive significance for an individual's health status.

Relationship Between Mean Leucocyte Telomere Length and Measures of Allostatic Load in US Reproductive-Aged Women, NHANES 1999-2002.

BACKGROUND: Reproductive health disparities may be partly explained by the cumulative effects of chronic stress experienced by socially disadvantaged groups. Although, telomere length (TL) and allostatic load score have each been used as biological markers of stress, the relationship between these two measures is unknown. METHODS: We investigated the association between leucocyte TL and allostatic load score in 1503 non-pregnant women (20-44 years) participating in the National Health and Nutrition Examination Survey, 1999-2002. We constructed six different allostatic load scores using either quartile- or clinical-based cut-points for 14 biomarkers based on previously published methods. We estimated associations between TL and allostatic load scores and component biomarkers using linear regression, also assessing interactions by race/ethnicity. RESULTS: After adjustment for age, longer TL was associated with higher HDL cholesterol and lower C-reactive protein and creatinine clearance; TL was not associated with the other component biomarkers. Shorter TL was associated with higher allostatic load scores for the two clinical cut-point-based scores after adjustment for age, but not the four scores based on quartile cut-points. Significant interactions by race/ethnicity were observed for TL and HbA1c and triglycerides, but not for other component biomarkers or allostatic load scores. CONCLUSIONS: Although TL and allostatic load score are both considered measures of cumulative stress, most component biomarkers and scores using quartile-based cut-points were not associated with TL. In reproductive-aged women, allostatic load scores using clinical-based cut-points were more strongly associated with TL compared with quartile-based scores.

Stochastic simulations of normal aging and Werner's syndrome.

Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner's syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling.

Socioeconomic status and cell aging in children.

Theory suggests that chronic stress associated with disadvantaged social status may lead to acceleration in the rate of decline in physiological functioning. The purpose of this study is to examine the association between parental socioeconomic status (SES) and leukocyte telomere length (LTL), a marker of cell aging, in children. We examined SES and LTL in 70 white and black US children aged 7-13 who participated in the community-based AMERICO (Admixture Mapping for Ethnic and Racial Insulin Complex Outcomes) study. LTL was assessed using the polymerase chain reaction (PCR) method. Parental education was positively associated with child LTL, net of controls for sex, age, race/ethnicity, and family income. Compared to children with at least one college-educated parent, children whose parents never attended college had telomeres shorter by 1,178 base pairs, which is roughly equivalent to 6 years of additional aging. Socioeconomic disparities in cell aging are evident in early life, long before the onset of age-related diseases.

Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis.

Telomere dysfunction and shortening induce chromosomal instability and tumorigenesis. In this study, we analyze the adrenocortical dysplasia (acd) mouse, harboring a mutation in Tpp1/Acd. Additional loss of p53 dramatically rescues the acd phenotype in an organ-specific manner, including skin hyperpigmentation and adrenal morphology, but not germ cell atrophy. Survival to weaning age is significantly increased in Acd(acd/acd) p53(-/-) mice. On the contrary, p53(-/-) and p53(+/-) mice with the Acd(acd/acd) genotype show a decreased tumor-free survival, compared with Acd(+/+) mice. Tumors from Acd(acd/acd) p53(+/-) mice show a striking switch from the classic spectrum of p53(-/-) mice toward carcinomas. The acd mouse model provides further support for an in vivo role of telomere deprotection in tumorigenesis.

The association between physical activity in leisure time and leukocyte telomere length.

BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.

No association between socio-economic status and white blood cell telomere length.

It has been hypothesized that more socio-economically deprived individuals age faster and, thus, have shorter telomeres than their more affluent counterparts. A weak association between white blood cell telomere length and socio-economic status in a large heterogeneous sample of females has recently been reported. In 318 individuals from a homogeneous birth cohort, we found no evidence of an association between any measure of socio-economic status and peripheral blood mononucleocyte telomere length at age 50 after control for lifestyle variables, gender and paternal age at birth. The results of this, and the previous study, suggest that there is little evidence of a strong or consistent correlation between white blood cell telomere length and markers of socio-economic status.

Assessment of telomere length and factors that contribute to its stability.

Short strands of tandem hexameric repeats known as telomeres cap the ends of linear chromosomes. These repeats protect chromosomes from degradation and prevent chromosomal end-joining, a phenomenon that could occur due to the end-replication problem. Telomeres are maintained by the activity of the enzyme telomerase. The total number of telomeric repeats at the terminal end of a chromosome determines the telomere length, which in addition to its importance in chromosomal stabilization is a useful indicator of telomerase activity in normal and malignant tissues. Telomere length stability is one of the important factors that contribute to the proliferative capacity of many cancer cell types; therefore, the detection and estimation of telomere length is extremely important. Until relatively recently, telomere lengths were analyzed primarily using the standard Southern blot technique. However, the complexities of this technique have led to the search for more simple and rapid detection methods. Improvements such as the use of fluorescent probes and the ability to sort cells have greatly enhanced the ease and sensitivity of telomere length measurements. Recent advances, and the limitations of these techniques are evaluated. Drugs that assist in telomere shortening may contribute to tumor regression. Therefore, factors that contribute to telomere stability may influence the efficiency of the drugs that have potential in cancer therapy. These factors in relation to telomere length are also examined in this analysis.