Examining the influence of adversity, family contexts, and a family-based intervention on parent and child telomere length.

Background: Exposure to adversity, trauma, and negative family environments can prematurely shorten telomeres, the protective caps at the ends of chromosomes. Conversely, some evidence indicates that positive environments and psychosocial interventions can buffer the shortening of telomere length (TL). However, most work has examined individual aspects of the family environment as predictive of TL with little work investigating multiple risk and protective factors. Further, most research has not examined parent TL relative to child TL despite its heritability. Objective: In the current study, we examined interparental conflict, positive parenting, alcohol use, adverse childhood experiences (ACEs), and a family-based intervention as predictive of parent TL. We also examined interparental conflict, positive parenting, ACEs, and a family-based intervention as predictive of child TL. Method: Parents and adolescents from a sample of divorced families participated in either a 10-session family-based intervention, the New Beginnings Programme (NBP), or a 2-week active control condition. Approximately six years after the intervention, a subsample of parents (n = 45) and adolescents (n = 41) were assessed for TL. Parents reported on interparental conflict, ACEs, and alcohol use. Children reported on interparental conflict, positive parenting, and ACEs. In separate models, these constructs and the NBP intervention condition were examined as predictors of parent TL and child TL. Results: Findings indicated that the family-based intervention was associated with longer TL in parents. Also, positive parenting was associated with longer TL in children. Conclusions: These findings have important implications for the role of the family and family-based preventive interventions in buffering parent and child biological stress. HIGHLIGHTS: Across multiple indices of psychosocial functioning, we found a family-based intervention associated with longer telomere length in parents and positive parenting associated with longer telomere length in children.

Antecedentes: La exposición a la adversidad, el trauma y los entornos familiares negativos pueden acortar prematuramente los telómeros, las tapas protectoras en los extremos de los cromosomas. Por el contrario, algunas pruebas indican que los entornos positivos y las intervenciones psicosociales pueden amortiguar el acortamiento de la longitud de los telómeros (LT). Sin embargo, la mayor parte del trabajo ha examinado aspectos individuales del entorno familiar como predictivo de LT con pocos trabajos que investiguen múltiples factores de riesgo y protección. Además, la mayoría de las investigaciones no han examinado la LT de los padres en relación con la LT del niño a pesar de su heredabilidad.Objetivo: En el estudio actual, examinamos el conflicto interparental, la crianza positiva, el consumo de alcohol, las experiencias infantiles adversas (ACE, por sus siglas en inglés) y una intervención basada en la familia como predictores de LT de los padres. También examinamos el conflicto interparental, la crianza positiva, las ACE y una intervención basada en la familia como predictores de LT infantil.Método: Los padres y los adolescentes de una muestra de familias divorciadas participaron en una intervención familiar de 10 sesiones, el nombre de la intervención está oculto para su revisión, o en una condición de control activo de 2 semanas. Aproximadamente seis años después de la intervención, se evaluó la longitud de los telómeros en una submuestra de padres (n = 45) y adolescentes (n = 41). Los padres informaron sobre conflictos entre padres, ACE y consumo de alcohol. Los niños informaron sobre conflictos entre padres, crianza positiva y ACE. En modelos separados, estos constructos y la condición de intervención nombre oculto para su revisión se examinaron como predictores de LT de padres y LT de niños.Resultados: Los hallazgos indicaron que la intervención basada en la familia se asoció con una LT más prolongada en los padres. Además, la crianza positiva se asoció con una LT más prolongada en los niños.Conclusiones: Estos hallazgos tienen implicaciones importantes para el papel de la familia y las intervenciones preventivas basadas en la familia para amortiguar el estrés biológico de padres e hijos.

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.

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.

Testing for paternal influences on offspring telomere length in a human cohort in the Philippines.

OBJECTIVES: Telomeres, emerging biomarkers of aging, are comprised of DNA repeats located at chromosomal ends that shorten with cellular replication and age in most human tissues. In contrast, spermatocyte telomeres lengthen with age. These changes in telomere length (TL) appear to be heritable, as older paternal ages of conception (PAC) predict longer offspring TL. Mouse-model studies raise questions about the potential for effects of paternal experiences on human offspring TL, as they suggest that smoking, inflammation, DNA damage, and stressors all shorten sperm TL. Here, we examined whether factors from the paternal environment predict offspring TL as well as interact with PAC to predict offspring TL. MATERIALS AND METHODS: Using data from the Philippines, we tested if smoking, psychosocial stressors, or shorter knee height (a measure of early life adversity) predict shorter offspring TL. We also tested if these interacted with PAC in predicting offspring TL. RESULTS: While we did not find the predicted associations, we observed a trend toward fathers with shorter knee height having offspring with longer TL. In addition, we found that knee height interacted with PAC to predict offspring TL. Specifically, fathers with shorter knee heights showed a stronger positive effect of PAC on offspring TL. DISCUSSION: While the reasons for these associations remain uncertain, shorter knee height is characteristic of earlier puberty. Since spermatocyte TL increases with the production of sperm, we speculate that individuals with earlier puberty, and its concomitant commencement of production of sperm, had more time to accumulate longer sperm telomeres.

Shortened telomere length is associated with unfair treatment attributed to race in African Americans living in Tallahassee, Florida.

OBJECTIVES: Experiences of interpersonal discrimination are pervasive stressors in the lives of African Americans. Increased discrimination stress may cause premature aging. Telomere length (TL) is a plastic genetic trait that is an emerging indicator of cellular health and aging. Short TL is a risk factor for the earlier onset of disease. TL shortens with age, a process that may be accelerated by psychosocial stress. Our study explores the relationship between TL and experiences of discrimination in the form of self-reported unfair treatment (UT). METHODS: Using a qPCR-based method, we measured TL in DNA from saliva samples provided by 135 African American adults from Tallahassee, FL. We developed discrimination measures using a modified survey that explores nine social domains of self-reported unfair treatment experienced both directly and indirectly. We used multiple regression to examine associations between UT and TL. RESULTS: We found that racial discrimination in the form of self-reported unfair treatment attributed to race (UT-Race-Self) is inversely associated with TL. CONCLUSIONS: The significant association between increased UT-Race-Self and shorter telomeres supports the hypothesis that psychosocial stress stemming from racial discrimination may affect TL. The potential impact of discrimination on TL may contribute to premature biological aging and racial health inequalities seen in African Americans.

Older paternal ages and grandpaternal ages at conception predict longer telomeres in human descendants.

Telomere length (TL) declines with age in most human tissues, and shorter TL appears to accelerate senescence. By contrast, men's sperm TL is positively correlated with age. Correspondingly, in humans, older paternal age at conception (PAC) predicts longer offspring TL. We have hypothesized that this PAC effect could persist across multiple generations, and thereby contribute to a transgenerational genetic plasticity that increases expenditures on somatic maintenance as the average age at reproduction is delayed within a lineage. Here, we examine TL data from 3282 humans together with PAC data across four generations. In this sample, the PAC effect is detectable in children and grandchildren. The PAC effect is transmitted through the matriline and patriline with similar strength and is characterized by a generational decay. PACs of more distant male ancestors were not significant predictors, although statistical power was limited in these analyses. Sensitivity analyses suggest that the PAC effect is linear, not moderated by offspring age, or maternal age, and is robust to controls for income, urbanicity and ancestry. These findings show that TL reflects the age at the reproduction of recent male matrilineal and patrilineal ancestors, with an effect that decays across generations.

Years of caregiving for chronically ill and disabled family members is not associated with telomere length in the Philippines.

BACKGROUND: Caring for chronically disabled family members is a stressful experience. In turn, psychosocial stress is linked to premature aging. Telomere length (TL) is a plastic genetic trait that is a biomarker of aging, and a possible mechanism linking psychosocial stress and accelerated aging. METHODS: TL was measured using qPCR method from blood samples in 1233 Filipino adults from Cebu, Philippines. Caregiving was measured as chronicity of care, or the sum total number of years an individual was the primary caregiver for any household member with a chronic illness or disability. Linear regression models were used to test for associations between chronicity of care and TL. Interaction terms were used to test whether or not the association between chronicity of care and TL differed by sex, age, and relationship to the caregiver. Specific statistical designs were publicly pre-registered before analysis began. RESULTS: Chronicity of care was not associated with TL. Neither did we find any evidence for caregiving varying in its effect on TL by caregiver sex, age, or relationship to the chronically ill/disabled. CONCLUSIONS: We found no evidence of an association between chronicity of care and TL. This result coupled with a recent study of a similarly sized cohort suggests that previous significant results linking caregiving and TL may be due to very particular types of caregiving populations or are possibly artifacts of small sample sizes.

Understanding influences of culture and history on mtDNA variation and population structure in three populations from Assam, Northeast India.

OBJECTIVES: Positioned at the nexus of India, China, and Southeast Asia, Northeast India is presumed to have served as a channel for land-based human migration since the Upper Pleistocene. Assam is the largest state in the Northeast. We characterized the genetic background of three populations and examined the ways in which their population histories and cultural practices have influenced levels of intrasample and intersample variation. METHODS: We examined sequence data from the mtDNA hypervariable control region and selected diagnostic mutations from the coding region in 128 individuals from three ethnic groups currently living in Assam: two Scheduled tribes (Sonowal Kachari and Rabha), and the non-Scheduled Tai Ahom. RESULTS: The populations of Assam sampled here express mtDNA lineages indicative of South Asian, Southeast Asian, and East Asian ancestry. We discovered two completely novel haplogroups in Assam that accounted for 6.2% of the lineages in our sample. We also identified a new subhaplogroup of M9a that is prevalent in the Sonowal Kachari of Assam (19.1%), but not present in neighboring Arunachal Pradesh, indicating substantial regional population structuring. Employing a large comparative dataset into a series of multidimensional scaling (MDS) analyses, we saw the Rabha cluster with populations sampled from Yunnan Province, indicating that the historical matrilineality of the Rabha has maintained lineages from Southern China. CONCLUSION: Assam has undergone multiple colonization events in the time since the initial peopling event, with populations from Southern China and Southeast Asia having the greatest influence on maternal lineages in the region.

Patterns of Congenital Malformations and Barriers to Care in Eastern Democratic Republic of Congo.

BACKGROUND: An increase of congenital anomalies in the eastern Democratic Republic of the Congo (DRC) has been reported. Congenital malformations (CMs) are not uncommon among newborns and, if left untreated, can contribute to increased neonate morbidity and mortality. METHODS: Medical records of all individuals admitted with a diagnosed CM to HEAL Africa Teaching Hospital (Goma, DRC) from 2002 to 2014 (n=1301) were reviewed. Data were analysed using descriptive statistics to summarize chart records, and inferential statistics to investigate significant barriers to earlier treatment. RESULTS: Since 2012, the number of patients treated each year for CMs has increased by over 200% compared to the average annual number of cases treated from 2002-2011. Though delayed presentation of patients to HEAL Hospital was very obvious, with an average age of 8.2 years. We find that patient age has been significantly decreasing (p=0.037) over time. The average distance separating patients from HEAL Hospital was 178 km, with approximately one third living 350 km or further from the treatment center. Distance is the most significant (p=3.33x10(-6)) barrier to earlier treatment. When controlling for an interaction between gender and the use of mercy funds, we also find that female patients are at a significant (p=1.04x10(-3)) disadvantage to undergo earlier corrective surgery. This disadvantage is further illustrated by our finding that 89% of women and girls, and over 81% of all patients, required mercy funds to cover the cost of surgery in 2014. Lastly, the mortality rate for surgery was low and averaged less than 1.0%. CONCLUSION: Despite a formal end to the war in 2009, and an overall increase in individuals undergoing corrective surgery, distance, poverty, and gender are still massive barriers to CM care at HEAL Hospital, Goma, DRC. We find that patients have been successfully treated earlier by HEAL, although the average age of CM correction in 2014 (4.9 years) is still above average for Sub-Saharan Africa. Thus, we advocate for further funding from the National Government and international health agencies to enable continued treatment of CMs in rural residents of the eastern DRC. Distance, the most significant barrier to care can be mitigated by the implementation of additional mobile clinics and the construction of regional surgery centers along with the associated hiring of surgeons trained in CM repair.