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.

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 1,233 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

BackgroundAn 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.ResultsSince 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%.ConclusionDespite 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.

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.

Objectives: Telomeres are the protective caps of chromosomes. They shorten with cell replication, age, and possibly environmental stimuli (e.g., 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 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 (BC). 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 seven 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 (i.e., strongest overall association with both VWB TL and age), followed by saliva, and then BC. Conclusions: Measuring TL using DNA isolated from DBS is the best option for minimally-invasively collected samples, which can be used to expand research to diverse settings and populations.

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.

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. K E Y W O R D Sepigenetics, intergenerational effects, intergenerational inertia, intergenerational plasticity, senescence

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