Publications by authors named "Jue Lin"

159 Publications

Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes.

Neurobiol Stress 2021 Nov 9;15:100407. Epub 2021 Oct 9.

Center for Neuroscience in Women's Health, Stanford University, Palo Alto, USA.

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone. Herein, we report that i) subjects with MDD and shorter leukocyte telomere length (LTL) show decreased levels of LAC, increased BMI, and a history of specific types of childhood trauma; and that ii) these multidimensional factors spanning mitochondrial metabolism, cellular aging, metabolic function, and childhood trauma provide more detailed signatures to predict longitudinal changes in depression severity in response to pioglitazone than individual factors. The findings of multidimensional signatures involved in the pathophysiology of depression and their role in predicting treatment outcomes provide a starting point for the development of a mechanistic framework linking biological networks and environmental factors to clinical outcomes in pursuit of personalized medicine strategies to effectively treat MDD.
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http://dx.doi.org/10.1016/j.ynstr.2021.100407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592929PMC
November 2021

Blood-based mitochondrial respiratory chain function in major depression.

Transl Psychiatry 2021 Nov 17;11(1):593. Epub 2021 Nov 17.

Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Psychiatry, Lund, Sweden.

Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity-the Mitochondrial Health Index (MHI)-has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.
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http://dx.doi.org/10.1038/s41398-021-01723-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599473PMC
November 2021

Stress and telomere shortening: Insights from cellular mechanisms.

Authors:
Jue Lin Elissa Epel

Ageing Res Rev 2021 Nov 1;73:101507. Epub 2021 Nov 1.

UCSF Department of Psychiatry and Behavioral Sciences, San Francisco, CA, United States.

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.
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http://dx.doi.org/10.1016/j.arr.2021.101507DOI Listing
November 2021

The COVID-19 Vaccination Hesitancy Among the People With Inflammatory Bowel Disease in China: A Questionnaire Study.

Front Public Health 2021 11;9:731578. Epub 2021 Oct 11.

Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

To explore the attitudes and views of patients with inflammatory bowel disease (IBD) on COVID-19 vaccination. An online interview questionnaire concerning the acceptance or hesitancy toward vaccination for COVID-19 was designed and 543 patients with IBD in China were invited to complete the structured self-administered anonymous questionnaire. Of all the participants, 50.7% were indecisive about the vaccination and only 16.0% opted for it. Vaccination hesitancy was significantly associated with women and those without medical or biomedical backgrounds. The acceptance of COVID-19 vaccination was higher in participants with no history of immune-modifying therapies, especially in those without immunosuppressants. Participants who considered vaccination critically important to self-health or the health of others were more likely to choose immediately or later vaccination. Safety and potential adverse reactions, personal hypoimmunity, efficacy, and reliability of COVID-19 vaccines were the top three concerns of the participants that were independent of their willingness for vaccination. This study discloses the presence of hesitancy for COVID-19 vaccination in patients with IBD. Further studies are warranted to evaluate the efficacy and safety of COVID-19 vaccines in IBD individuals, with a specific focus on the impact of immune-modifying therapies. Health education and recommendation from authoritative sources may facilitate COVID-19 vaccination efforts.
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http://dx.doi.org/10.3389/fpubh.2021.731578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542757PMC
November 2021

Telomere length is associated with growth in children in rural Bangladesh.

Elife 2021 09 8;10. Epub 2021 Sep 8.

Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, United States.

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.

Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.

Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.

Conclusions: Consistent with the , our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.

Funding: Funded by the Bill and Melinda Gates Foundation.

Clinical Trial Number: NCT01590095.
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http://dx.doi.org/10.7554/eLife.60389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494482PMC
September 2021

Longitudinal Associations Between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis.

J Gerontol A Biol Sci Med Sci 2021 Jul 20. Epub 2021 Jul 20.

Division of Epidemiology, School of Public Health, University of California Berkeley, USA.

Background: We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in leukocyte telomere length (LTL).

Methods: Data are from the Multi-Ethnic Study of Atherosclerosis (N = 1064; age range 45-84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, ≥2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract-defined neighborhoods. 10-year change in LTL was defined as regression to the mean-corrected 10-year difference in the ratio of telomeric DNA to a single-copy gene (T/S).

Results: In linear mixed-effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(χ 2) = .01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in ≥2 domains was associated with faster LTL attrition over 10 years, compared to reporting no discrimination (β = -0.03; 95% confidence interval: -0.06, -0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.

Conclusions: Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.
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http://dx.doi.org/10.1093/gerona/glab193DOI Listing
July 2021

Alterations of cellular aging markers in obsessive- compulsive disorder: mitochondrial DNA copy number and telomere length.

J Psychiatry Neurosci 2021 Jul 22;46(4):E451-E458. Epub 2021 Jul 22.

From the Department of Psychiatry and Institute of Behavioural Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea (Kang, S.-T. Kim, S.-J. Kim); the Department of Psychiatry, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea (Park); the Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA (Lin); and the Department of Medical Education, Yonsei University College of Medicine, Seoul, South Korea (H.-W. Kim).

Background: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length - key markers of cellular aging - were altered in male and female participants with obsessive-compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index.

Methods: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts.

Results: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks λ = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks λ = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio.

Limitations: The present cross-sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers.

Conclusion: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD.
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http://dx.doi.org/10.1503/jpn.200238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519490PMC
July 2021

Longitudinal Associations between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis (MESA).

J Gerontol A Biol Sci Med Sci 2021 Jul 20. Epub 2021 Jul 20.

Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, CA.

Background: We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in Leukocyte Telomere Length (LTL).

Methods: Data are from the Multi-Ethnic Study of Atherosclerosis (MESA; N=1,064; age range 45-84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, ≥2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract defined neighborhoods. 10-year change in LTL was defined as Regression to the Mean corrected 10-year difference in the ratio of telomeric DNA to a single copy gene (T/S).

Results: In linear mixed effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(χ 2)=0.01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in ≥2 domains was associated with faster LTL attrition over 10-years, compared to reporting no discrimination (β=-0.03; 95% CI: -0.06, -0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion.

Conclusions: Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.
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http://dx.doi.org/10.1093/gerona/glab193DOI Listing
July 2021

Longer Leukocyte Telomere Length Predicts Stronger Response to a Workplace Sugar-Sweetened Beverage Sales Ban: An Exploratory Study.

Curr Dev Nutr 2021 Jul 26;5(7):nzab084. Epub 2021 May 26.

Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.

Background: Shorter leukocyte telomere length (LTL) is associated with increased risk of a number of metabolic diseases including insulin resistance and the development of type 2 diabetes mellitus. Shorter LTL is also associated with stress reactivity suggestive of a possible role for LTL to predict response to behavioral interventions. However, few studies have evaluated how interventions, such as weight loss or dietary changes, are associated with LTL changes or whether LTL can predict behavioral responses to interventions.

Objectives: We evaluated metabolic changes in relation to LTL changes and LTL at baseline in a cohort of at-risk adults in response to a 10-mo workplace-based sugar-sweetened beverage (SSB) intervention.

Methods: At baseline, metabolic health and LTL measurements were assessed through standard blood draws on 212 participants. Multivariable linear regression models were used to assess changes in anthropometrics, SSB consumption, and 13 blood-based metabolic risk factors, in relation to LTL at baseline and changes in LTL.

Results: Longer LTL at baseline was associated with decreases in SSB consumption over the 6-mo follow-up period (B = -29.67; = 0.04). Slower LTL attrition rates were associated with decreases in waist circumference (B = -0.27;   = 0.03), HDL cholesterol (B = -0.20;   = 0.05), and apoA1 (B = -0.09;  = 0.01).

Conclusions: Longer LTL at baseline predicted a favorable overall response to a behavioral intervention: decreases in SSB consumption. Abdominal adiposity losses paralleled slower declines in LTL suggestive of overall health benefits, but we found differences in the relations between metabolic changes and LTL at baseline compared with LTL attrition rates. Longer LTL may be a proxy marker of a positive behavioral response.This trial was registered at clinicaltrials.gov as NCT02585336.
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http://dx.doi.org/10.1093/cdn/nzab084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257411PMC
July 2021

Family socioeconomic status and child telomere length among the Samburu of Kenya.

Soc Sci Med 2021 08 1;283:114182. Epub 2021 Jul 1.

Department of Biochemistry and Biophysics, University of California, San Francisco, USA.

Previous research in high-income countries suggests that children from families with lower socioeconomic status (SES) tend to have shorter telomere length - a biomarker of stress and cell aging - than children from families with greater social and economic resources. However, little is known about predictors of child telomere length in low-income settings. Data for the current study are from a sample of 214 Samburu children aged 1-9 years. The Samburu are semi-nomadic pastoralists who live in the Rift Valley of north-central Kenya. Samburu livelihood is based primarily on livestock, and polygynous marriage is common. Drawing on prior ethnographic research, we measured 14 culturally relevant indicators of family SES, including mother's education, head of household's education, whether the child is currently attending school, household spending, mother's employment history, head of household's employment history, mother's perceived wealth, whether the child lives in a modern house, livestock holdings (total, cows, sheep/goats, and camels), mother's wife number, and whether the child lives in a polygynous household. Telomere length was measured in salivary DNA by the quantitative polymerase chain reaction (qPCR) method. Using latent class analysis, we identified four groups of children that are similar based on the 14 indicators of family SES: Lower SES; Middle SES, Traditional; Middle SES, Modern; and Higher SES. SES classes were not significantly associated with child telomere length. In models examining individual indicators of SES, we found that telomere length was 0.57 standard deviations greater for children who lived in families in the lowest quartile of total livestock holdings compared to those in the highest quartile (b = 0.57, p = 0.03). While additional research is needed to identify the mechanisms underlying this counterintuitive finding, the current study highlights the importance of cultural context in shaping the social gradient in health.
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http://dx.doi.org/10.1016/j.socscimed.2021.114182DOI Listing
August 2021

Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults.

Mol Psychiatry 2021 Jul 20;26(7):3034-3042. Epub 2021 Apr 20.

Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH, USA.

Higher levels of omega-3 track with longer telomeres, lower inflammation, and blunted sympathetic and cardiovascular stress reactivity. Whether omega-3 supplementation alters the stress responsivity of telomerase, cortisol, and inflammation is unknown. This randomized, controlled trial examined the impact of omega-3 supplementation on cellular aging-related biomarkers following a laboratory speech stressor. In total, 138 sedentary, overweight, middle-aged participants (n = 93 women, n = 45 men) received either 2.5 g/d of omega-3, 1.25 g/d of omega-3, or a placebo for 4 months. Before and after the trial, participants underwent the Trier Social Stress Test. Saliva and blood samples were collected once before and repeatedly after the stressor to measure salivary cortisol, telomerase in peripheral blood lymphocytes, and serum anti-inflammatory (interleukin-10; IL-10) and pro-inflammatory (interleukin-6; IL-6, interleukin-12, tumor necrosis factor-alpha) cytokines. Adjusting for pre-supplementation reactivity, age, sagittal abdominal diameter, and sex, omega-3 supplementation altered telomerase (p = 0.05) and IL-10 (p = 0.05) stress reactivity; both supplementation groups were protected from the placebo group's 24% and 26% post-stress declines in the geometric means of telomerase and IL-10, respectively. Omega-3 also reduced overall cortisol (p = 0.03) and IL-6 (p = 0.03) throughout the stressor; the 2.5 g/d group had 19% and 33% lower overall cortisol levels and IL-6 geometric mean levels, respectively, compared to the placebo group. By lowering overall inflammation and cortisol levels during stress and boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and reduce depression risk. ClinicalTrials.gov identifier: NCT00385723.
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http://dx.doi.org/10.1038/s41380-021-01077-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510994PMC
July 2021

Telomere length is associated with HIV infection, methamphetamine use, inflammation, and comorbid disease risk.

Drug Alcohol Depend 2021 04 16;221:108639. Epub 2021 Feb 16.

Department of Medicine University of California San Diego, 9500 Gilman Drive La Jolla, CA, 92093, USA.

Background: HIV infection and methamphetamine dependence (METH) are each associated with inflammation and premature aging, but their impact on biological aging is difficult to measure. Here we examined the impact of HIV and METH on leukocyte telomere lengths (LTL), and the correlations between LTL and other aging biomarkers.

Methods: The study was a cross-sectional analysis of 161 individuals categorized by HIV and methamphetamine (METH) dependence status into four groups: HIV-METH- (n = 50), HIV-METH+ (n = 29), HIV + METH- (n = 40), and HIV + METH+ (n = 42). We analyzed the relationships of leukocyte telomere length (telomere to single copy gene [T/S] ratio) with demographic and clinical data as well as a panel of biomarkers of inflammation and endothelial activation measured in blood and cerebrospinal fluid (CSF).

Results: HIV and METH were independently associated with shorter T/S ratio, even after adjusting for demographics and leukocyte count (R = 0·59, p < 0·0001). Higher plasma C-reactive protein (p = 0·0036) and CSF VCAM-1 (p = 0·0080) were also associated with shorter T/S ratio. A shorter T/S ratio was associated with higher risk for cardiovascular disease (p < 0·0001) and stroke (p < 0·0001), worse motor functioning (p = 0·037) and processing speed (p = 0·023), more depressive symptoms (p = 0·013), and higher CSF neurofilament-light (p = 0·003).

Conclusions: HIV and METH dependence were each associated with shorter telomeres. After adjusting for demographics, HIV, and METH, T/S ratio remained associated with aging-related outcomes including neurocognitive impairment, neurodegeneration, risks of cardiovascular disease and stroke. While not establishing causality, this study supports using the T/S ratio as a biomarker for estimating the impact of HIV and comorbidities on long-term health.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026664PMC
April 2021

The association of maternal psychosocial stress with newborn telomere length.

PLoS One 2020 10;15(12):e0242064. Epub 2020 Dec 10.

Department of Environmental Science, Policy and Management and School of Public Health, University of California, Berkeley, CA, United States of America.

Background: Telomere length in early life predicts later length, and shortened telomere length among adults and children has been linked to increased risk of chronic disease and mortality. Maternal stress during pregnancy may impact telomere length of the newborn.

Methods: In a diverse cohort of 355 pregnant women receiving prenatal and delivery care services at two hospitals in San Francisco, California, we investigated the relationship between self-reported maternal psychosocial stressors during the 2nd trimester of pregnancy and telomere length (T/S ratio) in newborn umbilical cord blood leukocytes. We examined financial strain, food insecurity, high job strain, poor neighborhood quality, low standing in one's community, experience of stressful/traumatic life events, caregiving for a dependent family member, perceived stress, and unplanned pregnancy. We used linear regression and Targeted Minimum Loss-Based Estimation (TMLE) to evaluate the change in the T/S ratio associated with exposure to each stressor controlling for maternal age, education, parity, race/ethnicity, and delivery hospital.

Results: In TMLE analyses, low community standing (-0.09; 95% confidence interval [CI]-0.19 to 0.00) and perceived stress (-0.07; 95% CI -0.15 to 0.021 was marginally associated with shorter newborn telomere length, but the associations were not significant after adjusting for multiple comparisons. All linear regression estimates were not statistically significant. Our results also suggest that the association between some maternal stressors and newborn telomere length varies by race/ethnicity and infant sex.

Conclusions: This study is the first to examine the joint effect of multiple stressors during pregnancy on newborn TL using a flexible modeling approach.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242064PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728273PMC
January 2021

Neighborhood social environment and changes in leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA).

Health Place 2021 01 1;67:102488. Epub 2020 Dec 1.

Division of Epidemiology, School of Public Health, University of California Berkeley, 2121 Berkeley Way West #5302, Berkeley, CA, 94720, USA.

Given limited research on the impact of neighborhood environments on accelerated biological aging, we examined whether changes in neighborhood socioeconomic and social conditions were associated with change in leukocyte telomere length using 10 years of longitudinal data from the Multi-Ethnic Study of Atherosclerosis (years 2000-2011; N = 1031; mean age = 61, SD = 9.4). Leukocyte telomere length change was corrected for regression to the mean and neighborhood was defined as census tract. Neighborhood socioeconomic indicators (factor-based score of income, education, occupation, and wealth of neighborhood) and neighborhood social environment indicators (aesthetic quality, social cohesion, safety) were obtained from the U.S Census/American Community Survey and via study questionnaire, respectively. Results of linear mixed-effects models showed that independent of individual sociodemographic characteristics, each unit of improvement in neighborhood socioeconomic status was associated with slower telomere length attrition over 10-years (β = 0.002; 95% Confidence Interval (CI): 0.0001, 0.004); whereas each unit of increase in safety (β = -0.043; 95% CI: -0.069, -0.016) and overall neighborhood social environment score (β = -0.005; 95% CI: -0.009, -0.0004) were associated with more pronounced telomere attrition, after additionally adjusting for neighborhood socioeconomic status. This study provides support for considerations of the broader social and socioeconomic contexts in relation to biological aging. Future research should explore potential psychosocial mechanisms underlying these associations using longitudinal study designs with repeated observations.
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http://dx.doi.org/10.1016/j.healthplace.2020.102488DOI Listing
January 2021

HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women.

Brain Behav Immun 2021 02 19;92:49-56. Epub 2020 Nov 19.

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA; Carolina Stress Initiative, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address:

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been associated with altered immune function, but the underlying molecular mechanisms are unclear. Epigenetic processes, including DNA methylation, respond to the glucocorticoid end-products of the HPA axis (cortisol in humans) and could be involved in this neuroendocrine-immune crosstalk. Here we examined the extent to which variations in HPA axis regulation are associated with peripheral blood DNA (CpG) methylation changes in 57 chronically stressed caregivers and 67 control women. DNA methylation was determined with the Illumina 450k array for a panel of genes involved in HPA axis and immune function. HPA axis feedback was assessed with the low-dose dexamethasone suppression test (DST), measuring the extent to which cortisol secretion is suppressed by the synthetic glucocorticoid dexamethasone. After multiple testing correction in the entire cohort, higher post-DST cortisol, reflecting blunted HPA axis negative feedback, but not baseline waking cortisol, was associated with lower DNA methylation at eight TNF and two FKBP5 CpG sites. Caregiver group status was associated with lower methylation at two IL6 CpG sites. Since associations were most robust with TNF methylation (32% of the 450k-covered sites), we further examined functionality of this epigenetic signature in cultured peripheral blood mononuclear cells in 33 participants; intriguingly, lower TNF methylation resulted in higher ex vivo TNF mRNA following immune stimulation. Taken together, our findings link chronic stress and HPA axis regulation with epigenetic signatures at immune-related genes, thereby providing novel insights into how aberrant HPA axis function may contribute to heightened inflammation and disease risk.
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http://dx.doi.org/10.1016/j.bbi.2020.11.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897273PMC
February 2021

Association between micronutrients and maternal leukocyte telomere length in early pregnancy in Rwanda.

BMC Pregnancy Childbirth 2020 Nov 13;20(1):692. Epub 2020 Nov 13.

Department of Pediatrics, University of California San Francisco, San Francisco, USA.

Background: Exposure to environmental stressors can lead to shorter leukocyte telomere length and increase the risk of chronic diseases. Preservation of leukocyte telomere length by reducing oxidative stress exposure and reinforcing immunity may be a mechanism by which nutritional factors delay or prevent chronic disease development.

Methods: Healthy pregnant women (aged 18-45 years) at 9-15 weeks of gestation living in Gasabo District, Kigali, Rwanda, were recruited from 10 health centers for a prospective, longitudinal study from September to October 2017 to determine possible associations between nutrition health, infectious disease and leukocyte telomere length. Anthropometric and laboratory measurements were performed using standard procedures; sociodemographic parameters and health histories were assessed via surveys, and leukocyte telomere length was assessed using quantitative PCR expressed as the ratio of a telomeric product to a single-copy gene product (T/S).

Results: Mean gestational age of participants (n = 297) at enrollment was 13.04 ± 3.50 weeks, age was 28.16 ± 6.10 years and leukocyte telomere length was 1.16 ± 0.22 (T/S). Younger age; no schooling vs. primary schooling; and lower levels of ferritin, soluble transferrin receptors and retinol-binding protein were independent predictors of longer telomere length in multivariable models.

Conclusions: Leukocyte telomere length is an indicator of biological aging in pregnant Rwandan women. Maternal micronutrient status, specifically lower ferritin, soluble transferrin receptor levels, and retinol-binding protein levels were associated with longer maternal telomere length in contrast with some studies from North America and Europe. There were no associations between inflammation and infectious disease status and maternal leukocyte telomere length. Further studies are needed to enhance our understanding of the interplay between maternal nutritional status and infectious disease in relation to leukocyte telomere length in developing countries.
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http://dx.doi.org/10.1186/s12884-020-03330-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664098PMC
November 2020

Associations of prenatal maternal stress with measures of cognition in 7.5-month-old infants.

Dev Psychobiol 2021 Jul 9;63(5):960-972. Epub 2020 Nov 9.

Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Studies have shown that prenatal stress can negatively impact neurodevelopment, but little is known about its effect on early cognitive development. We assessed the impact of prenatal stress on cognition in 152 7.5-month-old infants using Cohen's Perceived Stress Scale (PSS), maternal telomere length (MTL), and a Stressful Life Events (SLE) Scale. A visual recognition memory task consisting of nine blocks, each with one familiarization trial (two identical stimuli) followed by two test trials (one familiar stimulus, one novel), was administered. Outcomes assessed included: average time looking at stimuli (measure: processing speed), time to reach looking time criterion (measure: attention), and the proportion of time looking at the novel stimulus (measure: recognition memory). We examined the association of each stress measure with each outcome adjusted for infant age and sex, which of the two stimuli in each set was novel, household income, and maternal age, education, and IQ. Higher prenatal stress was associated with shorter looking durations [PSS (β = -1.6, 95% CI: -2.5, -0.58); SLE (β = 0.58, 95% CI: -0.08, 1.24); MTL (β = 1.81, 95% CI: 0.18, 3.44)] and longer time to reach criterion [PSS (β = 9.1, 95% CI: 1.6, 16.6); SLE (β = 12.2, 95% CI: 1.9, 24.1); MTL (β = -23.1, 95% CI: -45.3, -0.9)], suggesting that higher prenatal stress is associated with decreased visual attention in infancy.
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http://dx.doi.org/10.1002/dev.22059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278565PMC
July 2021

Are long telomeres better than short? Relative contributions of genetically predicted telomere length to neoplastic and non-neoplastic disease risk and population health burden.

PLoS One 2020 8;15(10):e0240185. Epub 2020 Oct 8.

UCSF Department of Biochemistry and Biophysics, San Francisco, CA, United States of America.

Background: Mendelian Randomization (MR) studies exploiting single nucleotide polymorphisms (SNPs) predictive of leukocyte telomere length (LTL) have suggested that shorter genetically determined telomere length (gTL) is associated with increased risks of degenerative diseases, including cardiovascular and Alzheimer's diseases, while longer gTL is associated with increased cancer risks. These varying directions of disease risk have long begged the question: when it comes to telomeres, is it better to be long or short? We propose to operationalize and answer this question by considering the relative impact of long gTL vs. short gTL on disease incidence and burden in a population.

Methods And Findings: We used odds ratios (OR) of disease associated with gTL from a recently published MR meta-analysis to approximate the relative contributions of gTL to the incidence and burden of neoplastic and non-neoplastic disease in a European population. We obtained incidence data of the 9 cancers associated with long gTL and 4 non-neoplastic diseases associated with short gTL from the Institute of Health Metrics (IHME). Incidence rates of individual cancers from SEER, a database of United States cancer records, were used to weight the ORs in order to align with the available IHME data. These data were used to estimate the excess incidences due to long vs. short gTL, expressed as per 100,000 persons per standard deviation (SD) change in gTL. To estimate the population disease burden, we used the Disability Adjusted Life Years (DALY) metric from the IHME, a measure of overall disease burden that accounts for both mortality and morbidity, and similarly calculated the excess DALY associated with long vs. short gTL.

Results: Our analysis shows that, despite the markedly larger ORs of neoplastic disease, the large incidence of degenerative diseases causes the excess incidence attributable to gTL to balance that of neoplastic diseases. Long gTL is associated with an excess incidence of 94.04 cases/100,000 persons/SD (45.49-168.84, 95%CI) from the 9 cancer, while short gTL is associated with an excess incidence of 121.49 cases/100,000 persons/SD (48.40-228.58, 95%CI) from the 4 non-neoplastic diseases. When considering disease burden using the DALY metric, long gTL is associated with an excess 1255.25 DALYs/100,000 persons/SD (662.71-2163.83, 95%CI) due to the 9 cancers, while short gTL is associated with an excess 1007.75 DALYs/100,000 persons/SD (411.63-1847.34, 95%CI) due to 4 non-neoplastic diseases.

Conclusions: Our results show that genetically determined long and short telomere length are associated with disease risk and burden of approximately equal magnitude. These results provide quantitative estimates of the relative impact of genetically-predicted short vs. long TL in a human population, and provide evidence in support of the cancer-aging paradox, wherein human telomere length is balanced by opposing evolutionary forces acting to minimize both neoplastic and non-neoplastic diseases. Importantly, our results indicate that odds ratios alone can be misleading in different clinical scenarios, and disease risk should be assessed from both an individual and population level in order to draw appropriate conclusions about the risk factor's role in human health.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240185PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544094PMC
December 2020

Maternal Psychological Resilience During Pregnancy and Newborn Telomere Length: A Prospective Study.

Am J Psychiatry 2021 02 11;178(2):183-192. Epub 2020 Sep 11.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin (Verner, Buss, Entringer); Department of Psychiatry, San Francisco School of Medicine, University of California, San Francisco (Epel); Department of Psychology and Logopedics, University of Helsinki, Helsinki (Lahti-Pulkkinen, Räikkönen); Department of Public Health Solutions, THL National Institute for Health and Welfare, Helsinki and Oulu, Finland, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, and Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki (Kajantie); Department of Pediatrics and UC Irvine Development, Health, and Disease Research Program, University of California, Irvine (Buss, Wadhwa, Entringer); Department of Biochemistry and Biophysics (Lin, Blackburn) and Department of Microbiology and Immunology (Blackburn), University of California, San Francisco; Department of Psychiatry and Human Behavior, Department of Obstetrics and Gynecology, and Department of Epidemiology, School of Medicine, University of California, Irvine (Wadhwa).

Objective: In the context of the importance of elucidating the determinants of the initial, newborn setting of telomere length (TL), it is increasingly evident that maternal stress and stress-related processes during pregnancy play a major role. Although psychological resilience may function as a buffer, research in this area has not yet examined its potential role vis-à-vis that of stress. The authors examined the relationship between maternal psychological resilience during pregnancy and newborn TL.

Methods: In a sample of 656 mother-child dyads from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction cohort, multiple serial assessments were conducted over the course of pregnancy to quantify maternal stress, negative and positive emotional responses to pregnancy events, positive affect, and perceived social support. Principal component analysis identified two latent factors: stress and positivity. A measure of resilience was computed by regressing the positivity factor on the stress factor, in order to quantify positivity after accounting for stress. TL was measured using quantitative polymerase chain reaction in leukocytes extracted from cord blood shortly after birth. Linear regression was used to predict newborn TL from maternal resilience during pregnancy, adjusting for other potential determinants.

Results: Maternal stress significantly predicted shorter newborn TL (β=-0.079), and positivity significantly predicted longer TL (β=0.135). Maternal resilience (positivity accounting for stress) was significantly and positively associated with newborn TL (β=0.114, 95% CI=0.035, 0.189), with each standard deviation increase in resilience predicting 12% longer newborn TL.

Conclusions: The results indicate that maternal psychological resilience may exert a salubrious effect on offspring telomere biology and highlight the importance of enhancing maternal mental health and well-being during pregnancy.
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http://dx.doi.org/10.1176/appi.ajp.2020.19101003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855094PMC
February 2021

Effect of Combat Exposure and Posttraumatic Stress Disorder on Telomere Length and Amygdala Volume.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 07 31;5(7):678-687. Epub 2020 Mar 31.

Department of Psychiatry, University of California, San Francisco School of Medicine, San Francisco, California.

Background: Traumatic stress can adversely affect physical and mental health through neurobiological stress response systems. We examined the effects of trauma exposure and posttraumatic stress disorder (PTSD) on telomere length, a biomarker of cellular aging, and volume of the amygdala, a key structure of stress regulation, in combat-exposed veterans. In addition, the relationships of psychopathological symptoms and autonomic function with telomere length and amygdala volume were examined.

Methods: Male combat veterans were categorized as having PTSD diagnosis (n = 102) or no lifetime PTSD diagnosis (n = 111) based on the Clinician-Administered PTSD Scale. Subjects were assessed for stress-related psychopathology, trauma severity, autonomic function, and amygdala volumes by magnetic resonance imaging.

Results: A significant interaction was found between trauma severity and PTSD status for telomere length and amygdala volume after adjusting for multiple confounders. Subjects with PTSD showed shorter telomere length and larger amygdala volume than those without PTSD among veterans exposed to high trauma, while there was no significant group difference in these parameters among those exposed to low trauma. Among veterans exposed to high trauma, greater telomere shortening was significantly correlated with greater norepinephrine, and larger amygdala volume was correlated with more severe psychological symptoms and higher heart rates.

Conclusions: These data suggest that the intensity of the index trauma event plays an important role in interacting with PTSD symptomatology and autonomic activity in predicting telomere length and amygdala volume. These results highlight the importance of trauma severity and PTSD status in predicting certain biological outcomes.
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http://dx.doi.org/10.1016/j.bpsc.2020.03.007DOI Listing
July 2020

Deep Retinal Capillary Plexus Decreasing Correlated With the Outer Retinal Layer Alteration and Visual Acuity Impairment in Pathological Myopia.

Invest Ophthalmol Vis Sci 2020 04;61(4):45

,.

Purpose: The purpose of this study was to measure alterations of inner retinal microvascular density and outer retinal sublayer thicknesses in pathological myopia, and to correlate the measured parameters with best corrected visual acuity (BCVA).

Methods: Optical coherence tomography (OCT) and OCT angiography (OCTA) images of 21 control, 48 simple high myopia, and 22 pathological myopia eyes were analyzed to quantify the thicknesses of the outer retinal sublayers and the density of the inner retinal microvascular network that includes the superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP). Retinal sublayer thicknesses and microvascular densities were compared among the three groups, and correlations of sublayer thicknesses and microvascular densities with BCVA were determined.

Results: In pathological myopia, density of the DRCP, thicknesses of myoid and ellipsoid zone (MEZ), interdigitation zone and retinal pigment epithelium/Bruch complex (IZ + RPE), and choroid were lower than in simple high myopia (P < 0.05). The decreased DRCP density was correlated with thinner MEZ and IZ+RPE in pathological myopia (P < 0.05), but not in simple high myopia (P > 0.05). Simple linear regression showed that axial length, female, thicknesses of outer plexiform layer (OPL), MEZ, IZ + RPE, choroid, and density of the SRCP and DRCP were correlated with BCVA. In multiple regression analysis, worse BCVA was associated only with thinner MEZ, thinner choroid, and decreased DRCP (P < 0.05).

Conclusions: Alteration of inner retinal microvascular density and outer retinal sublayer thicknesses occurred in pathological myopia, especially decreased DRCP and thinner MEZ, which were significantly associated with worse BCVA.
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http://dx.doi.org/10.1167/iovs.61.4.45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401930PMC
April 2020

Early Life Stress, Frontoamygdala Connectivity, and Biological Aging in Adolescence: A Longitudinal Investigation.

Cereb Cortex 2020 06;30(7):4269-4280

Department of Psychology, Stanford University, Stanford, CA 94305, USA.

Early life stress (ELS) may accelerate frontoamygdala development related to socioemotional processing, serving as a potential source of resilience. Whether this circuit is associated with other proposed measures of accelerated development is unknown. In a sample of young adolescents, we examined the relations among ELS, frontoamygdala circuitry during viewing of emotional faces, cellular aging as measured by telomere shortening, and pubertal tempo. We found that greater cumulative severity of ELS was associated with stronger negative coupling between bilateral centromedial amygdala and the ventromedial prefrontal cortex, a pattern that may reflect more mature connectivity. More negative frontoamygdala coupling (for distinct amygdala subdivisions) was associated with slower telomere shortening and pubertal tempo over 2 years. These potentially protective associations of negative frontoamygdala connectivity were most pronounced in adolescents who had been exposed to higher ELS. Our findings provide support for the formulation that ELS accelerates maturation of frontoamygdala connectivity and provide novel evidence that this neural circuitry confers protection against accelerated biological aging, particularly for adolescents who have experienced higher ELS. Although negative frontoamygdala connectivity may be an adaptation to ELS, frontoamygdala connectivity, cellular aging, and pubertal tempo do not appear to be measures of the same developmental process.
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http://dx.doi.org/10.1093/cercor/bhaa057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264647PMC
June 2020

Telomere length analysis from minimally-invasively collected samples: Methods development and meta-analysis of the validity of different sampling techniques: American Journal of Human Biology.

Am J Hum Biol 2021 01 18;33(1):e23410. Epub 2020 Mar 18.

Department of Anthropology, University of Washington, Seattle, Washington, USA.

Objectives: Telomeres are the protective caps of chromosomes. They shorten with cell replication, age, and possibly environmental stimuli (eg, infection and stress). Short telomere length (TL) predicts subsequent worse health. Although venous whole blood (VWB) is most commonly used for TL measurement, other, more minimally invasive, sampling techniques are becoming increasingly common due to their field-friendliness, allowing for feasible measurement in low-resource contexts. We conducted statistical validation work for measuring TL in dried blood spots (DBS) and incorporated our results into a meta-analysis evaluating minimally invasive sampling techniques to measure TL.

Methods: We isolated DNA extracts from DBS using a modified extraction protocol and tested how they endured different shipping conditions and long-term cryostorage. We then included our in-house DBS TL validation statistics (correlation values with VWB TL and age) in a series of meta-analyses of results from 24 other studies that published similar associations for values between TL measured in DBS, saliva, and buccal cells.

Results: Our modified DBS extraction technique produced DNA yields that were roughly twice as large as previously recorded. Partially extracted DBS DNA was stable for 7 days at room temperature, and still provided reliable TL measurements, as determined by external validation statistics. In our meta-analysis, DBS TL had the highest external validity, followed by saliva, and then buccal cells-possibly reflecting similarities/differences in cellular composition vs VWB.

Conclusions: DBS DNA is the best proxy for VWB from the three minimally-invasively specimen types evaluated and can be used to expand TL research to diverse settings and populations.
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http://dx.doi.org/10.1002/ajhb.23410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105084PMC
January 2021

Discrimination, social support, and telomere length: the Multi-Ethnic Study of Atherosclerosis (MESA).

Ann Epidemiol 2020 02 31;42:58-63.e2. Epub 2019 Dec 31.

Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, CA.

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 (χ) = 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.
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http://dx.doi.org/10.1016/j.annepidem.2019.12.009DOI Listing
February 2020

Impact of a nutritional supplement during gestation and early childhood on child salivary cortisol, hair cortisol, and telomere length at 4-6 years of age: a follow-up of a randomized controlled trial.

Stress 2020 09 24;23(5):597-606. Epub 2020 Feb 24.

Department of Nutrition, University of California, Davis, CA, USA.

Dysregulation of the stress response can occur early in life and may be affected by nutrition. Our objective was to evaluate the long-term effect of nutritional supplementation during gestation and early childhood on child cortisol and buccal telomere length (a marker of cellular aging) at 4-6 years of age. We conducted a follow-up study of children born to women who participated in a nutritional supplementation trial in Ghana. In one group, a lipid-based nutrient supplement (LNS) was provided to women during gestation and the first 6 months postpartum and to their infants from age 6 to 18 months. The control groups received either iron and folic acid (IFA) during gestation or multiple micronutrients during gestation and the first 6 months postpartum, with no infant supplementation. At age 4-6 years, we measured hair cortisol, buccal telomere length, and salivary cortisol before and after a stressor. Salivary cortisol was available for 364 children across all three trial arms and hair cortisol and telomere length were available for a subset of children ( = 275 and 278, respectively) from the LNS and IFA groups. Telomere length, salivary cortisol, and hair cortisol did not differ by supplementation group. Overall, these findings suggest that nutritional supplementation given during gestation and early childhood does not have an effect on child stress response or chronic stress in children at 4-6 years. ClinicalTrials.gov Identifier NCT00970866.Lay SummaryThis study addressed a research gap about whether improved nutrition during pregnancy and early childhood impacts telomere length and cortisol in preschool children. There was no difference in child telomere length or cortisol between two trial arms of a nutritional supplementation trial that began during pregnancy. The research outcomes indicate lipid-based nutrient supplements, a relatively new form of supplementation, do not have an effect on markers of stress or cellular aging measured in later childhood.
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http://dx.doi.org/10.1080/10253890.2020.1728528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497284PMC
September 2020

Racial discrimination and telomere shortening among African Americans: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Health Psychol 2020 Mar 13;39(3):209-219. Epub 2020 Jan 13.

Department of Psychiatry, University of California, San Francisco.

Objective: Telomeres are protective sequences of DNA capping the ends of chromosomes that shorten over time. Leukocyte telomere length (LTL) is posited to reflect the replicative history of cells and general systemic aging of the organism. Chronic stress exposure leads to accelerated LTL shortening, which has been linked to increased susceptibility to and faster progression of aging-related diseases. This study examined longitudinal associations between LTL and experiences of racial discrimination, a qualitatively unique source of minority psychosocial stress, among African Americans.

Method: Data are from 391 African Americans in the Coronary Artery Risk Development in Young Adults (CARDIA) Telomere Ancillary Study. We examined the number of domains in which racial discrimination was experienced in relation to LTL collected in Years 15 and 25 (Y15: 2000/2001; Y25: 2010/2011). Multivariable linear regression examined if racial discrimination was associated with LTL. Latent change score analysis (LCS) examined changes in racial discrimination and LTL in relation to one another.

Results: Controlling for racial discrimination at Y15, multivariable linear regression analyses indicated that racial discrimination at Y25 was significantly associated with LTL at Y25. This relationship remained robust after adjusting for LTL at Y15 (b = -.019, = .015). Consistent with this finding, LCS revealed that increases in experiences of racial discrimination were associated with faster 10-year LTL shortening (b = -.019, = .015).

Conclusions: This study adds to evidence that racial discrimination contributes to accelerated physiologic weathering and health declines among African Americans through its impact on biological systems, including via its effects on telomere attrition. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/hea0000832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373166PMC
March 2020

Depressive Symptoms Predict Change in Telomere Length and Mitochondrial DNA Copy Number Across Adolescence.

J Am Acad Child Adolesc Psychiatry 2020 12 16;59(12):1364-1370.e2. Epub 2019 Oct 16.

Stanford University, California.

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 Children's 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.
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http://dx.doi.org/10.1016/j.jaac.2019.09.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160006PMC
December 2020

Correlates of longitudinal leukocyte telomere length in the Costa Rican Longevity Study of Healthy Aging (CRELES): On the importance of DNA collection and storage procedures.

PLoS One 2019 11;14(10):e0223766. Epub 2019 Oct 11.

Escuela de Biología, Universidad de Costa Rica, San Jose, Costa Rica.

The objective is to identify cofactors of leukocyte telomere length (LTL) in a Latin American population, specifically the association of LTL with 36 socio-demographic, early childhood, and health characteristics, as well as with DNA sample collection and storage procedures. The analysis is based on longitudinal information from a subsample of 1,261 individuals aged 60+ years at baseline from the Costa Rican Study of Longevity and Healthy Aging (CRELES): a nationally representative sample of elderly population. Random effects regression models for panel data were used to estimate the associations with LTL and its longitudinal changes. Sample collection procedures and DNA refrigerator storage time were strongly associated with LTL: telomeres are longer in blood collected in October-December, in DNA extracted from <1-year-old blood cells, and in DNA stored at 4°C for longer periods of time up to five years. The data confirmed that telomeres are shorter at older ages, as well as among males, and diabetic individuals, whereas telomeres are longer in the high-longevity Nicoya region. Most health, biomarkers, and early childhood indicators did not show significant associations with LTL. Longitudinal LTL variation over approximately two years was mainly associated with baseline LTL levels, as found in other studies. Our findings suggest that if there is unavoidable variability in season of sample collection and DNA storage time, these factors should be controlled for in all demographic and epidemiologic studies of LTL. However, due to unobserved components of measurement variation, statistical control may be inadequate as compared to standardization of data collection procedures.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223766PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788698PMC
March 2020

Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults: A Randomized Clinical Trial.

JAMA Netw Open 2019 09 4;2(9):e199687. Epub 2019 Sep 4.

Social Neuroscience Lab, Max Planck Society, Berlin, Germany.

Importance: Telomere length is associated with the development of age-related diseases and structural differences in multiple brain regions. It remains unclear, however, whether change in telomere length is linked to brain structure change, and to what extent telomere length can be influenced through mental training.

Objectives: To assess the dynamic associations between leukocyte telomere length (LTL) and cortical thickness (CT), and to determine whether LTL is affected by a longitudinal contemplative mental training intervention.

Design, Setting, And Participants: An open-label efficacy trial of three 3-month mental training modules with healthy, meditation-naive adults was conducted. Data on LTL and CT were collected 4 times over 9 months between April 22, 2013, and March 31, 2015, as part of the ReSource Project. Data analysis was performed between September 23, 2016, and June 21, 2019. Of 1582 eligible individuals, 943 declined to participate; 362 were randomly selected for participation and assigned to training or retest control cohorts, with demographic characteristics matched. The retest control cohorts underwent all testing but no training. Intention-to-treat analysis was performed.

Interventions: Training cohort participants completed 3 modules cultivating interoception and attention (Presence), compassion (Affect), or perspective taking (Perspective).

Main Outcomes And Measures: Change in LTL and CT.

Results: Of the 362 individuals randomized, 30 participants dropped out before study initiation (initial sample, 332). Data were available for analysis of the training intervention in 298 participants (n = 222 training; n = 76 retest control) (175 women [58.7%]; mean [SD] age, 40.5 [9.3] years). The training modules had no effect on LTL. In 699 observations from all 298 participants, mean estimated changes in the relative ratios of telomere repeat copy number to single-copy gene (T/S) were for no training, 0.004 (95% CI, -0.010 to 0.018); Presence, -0.007 (95% CI, -0.025 to 0.011); Affect, -0.005 (95% CI, -0.019 to 0.010); and Perspective, -0.001 (95% CI, -0.017 to 0.016). Cortical thickness change data were analyzed in 167 observations from 67 retest control participants (37 women [55.2%], mean [SD] age, 39.6 [9.0] years). In this retest control cohort subsample, naturally occurring LTL change was related to CT change in the left precuneus extending to the posterior cingulate cortex (mean t161 = 3.22; P < .001; r = 0.246). At the individual participant level, leukocyte telomere shortening as well as lengthening were observed. Leukocyte telomere shortening was related to cortical thinning (t77 = 2.38; P = .01; r = 0.262), and leukocyte telomere lengthening was related to cortical thickening (t77 = 2.42; P = .009; r = 0.266). All analyses controlled for age, sex, and body mass index.

Conclusions And Relevance: The findings of this trial indicate an association between short-term change in LTL and concomitant change in plasticity of the left precuneus extending to the posterior cingulate cortex. This result contributes to the evidence that LTL changes more dynamically on the individual level than previously thought. Further studies are needed to determine potential long-term implications of such change in relation to cellular aging and the development of neurodegenerative disorders. No effect of contemplative mental training was noted in what may be, to date, the longest intervention with healthy adults.

Trial Registration: ClinicalTrials.gov identifier: NCT01833104.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.9687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763984PMC
September 2019

Corrigendum to "Loving-kindness meditation slows biological aging in novices: Evidence from a 12-week randomized controlled trial" [Psychoneuroendocrinology 108 (2019) (October) 20-27].

Psychoneuroendocrinology 2019 Nov 13;109:104440. Epub 2019 Sep 13.

Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB #3270, Chapel Hill, NC, 27599, USA. Electronic address:

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http://dx.doi.org/10.1016/j.psyneuen.2019.104440DOI Listing
November 2019
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