Telomere length and early severe social deprivation: linking early adversity and cellular aging.

Accelerated telomere length attrition has been associated with psychological stress and early adversity in adults; however, no studies have examined whether telomere length in childhood is associated with early experiences. The Bucharest Early Intervention Project is a unique randomized controlled trial of foster care placement compared with continued care in institutions. As a result of the study design, participants were exposed to a quantified range of time in institutional care, and represented an ideal population in which to examine the association between a specific early adversity, institutional care and telomere length. We examined the association between average relative telomere length, telomere repeat copy number to single gene copy number (T/S) ratio and exposure to institutional care quantified as the percent of time at baseline (mean age 22 months) and at 54 months of age that each child lived in the institution. A significant negative correlation between T/S ratio and percentage of time was observed. Children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood. Gender modified this main effect. The percentage of time in institutional care at baseline significantly predicted telomere length in females, whereas the percentage of institutional care at 54 months was strongly predictive of telomere length in males. This is the first study to demonstrate an association between telomere length and institutionalization, the first study to find an association between adversity and telomere length in children, and contributes to the growing literature linking telomere length and early adversity.

Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study.

STUDY QUESTION: Is the association between paternal age at birth and offspring leukocyte telomere length (LTL) an artifact of early life socioeconomic status (SES)? SUMMARY ANSWER: Indicators of early life SES did not alter the relationship between paternal age at birth and offspring LTL among a population of white female nurses. WHAT IS KNOWN ALREADY: Telomere length is considered a highly heritable trait. Recent studies report a positive correlation between paternal age at birth and offspring LTL. Maternal age at birth has also been positively associated with offspring LTL, but may stem from the strong correlation with paternal age at birth. STUDY DESIGN, SIZE AND DURATION: The Nurses' Health Study (NHS) is an ongoing prospective cohort study of 121 700 female registered nurses who were enrolled in 1976. Great effort goes into maintaining a high degree of follow-up among our cohort participants (>95% of potential person-years). In 1989-1990, a subset of 32 826 women provided blood samples from which we selected participants for several nested case-control studies of telomere length and incident chronic disease. We used existing LTL data on a total of 4250 disease-free women who also reported maternal and paternal age at birth for this study. PARTICIPANTS/MATERIALS, SETTING AND METHODS: Nested case-control studies of stroke, myocardial infarction, cancers of the breast, endometrium, skin, pancreas and colon, as well as colon adenoma, were conducted within the blood sub-cohort. Each study used the following study design: for each case of a disease diagnosed after blood collection, a risk-set sampling scheme was used to select from one to three controls from the remaining participants in the blood sub-cohort who were free of that disease when the case was diagnosed. Controls were matched to cases by age at blood collection (± 1 year), date of blood collection (± 3 months), menopausal status, recent postmenopausal hormone use at blood collection (within 3 months, except for the myocardial infarction case-control study), as well as other factors carefully chosen for each individual study. The current analysis was limited to healthy controls. We also included existing LTL data from a small random sample of women participating in a cognitive sub-study. LTL was measured using the quantitative PCR-based method. Exposure and covariate information are extracted from biennial questionnaires completed by the participants. MAIN RESULTS AND THE ROLE OF CHANCE: We found a strong association between paternal age at birth and participant LTL (P = 1.6 × 10(-5)) that remained robust after controlling for indicators of early life SES. Maternal age at birth showed a weak inverse association with participant LTL after adjusting for age at blood collection and paternal age at birth (P = 0.01). We also noted a stronger association between paternal age at birth and participant LTL among premenopausal than among postmenopausal women (P(interaction) = 0.045). However, this observation may be due to chance as premenopausal women represented only 12.6% (N = 535) of the study population and LTL was not correlated with age at menopause, total or estrogen-only hormone therapy (HT) use suggesting that changes in in vivo estrogen exposure do not influence telomere length regulation. LIMITATIONS AND REASONS FOR CAUTION: The women in our study are not representative of the general US female population, with an underrepresentation of non-white and low social class groups. Although the interaction was not significant, we noted that the paternal age at birth association with offspring LTL appeared weaker among women whose parents did not own their home at the time of the participant's birth. As telomere dynamics may differ among individuals who are most socioeconomically deprived, SES indicators may have more of an influence on the relationship between paternal age at birth and offspring LTL in such populations. WIDER IMPLICATIONS OF THE FINDINGS: As of yet, our and prior studies have not identified childhood or adult characteristics that confound the paternal age at birth association with offspring LTL, supporting the hypothesis that offspring may inherit the longer telomeres found in sperm of older men. The biological implications of the paternal age effect are unknown. A recent theory proposed that the inheritance of longer telomere from older men may be an adaptive signal of reproductive lifespan, while another theory links telomere length attrition to female reproductive senescence. However, we are unaware of any data to substantiate a relationship between paternal age at birth and daughter's fertility. Generalizability of our study results to other white female populations is supported by prior reports of paternal age at birth and offspring telomere length. Furthermore, a confounding relationship between paternal or maternal age at birth and SES was not observed in a study of SES and telomere length. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institutes of Health (grants numbers: CA87969, CA49449, CA065725, CA132190, CA139586, HL088521, CA140790, CA133914, CA132175, ES01664 to M.D.); and by the American Health Association Foundation. We have no competing interests to declare.

Endoscopic submucosal dissection of gastric lesions by using a master and slave transluminal endoscopic robot: an animal survival study.

BACKGROUND AND STUDY AIMS: The feasibility of performing endoscopic submucosal dissection (ESD) using the Master and Slave Transluminal Endoscopic Robot (MASTER), a robotics-enhanced surgical system, has been shown in our previous study. This study aimed to further explore, in an animal survival study, the 2-week outcome of using MASTER to perform ESD. PATIENTS AND METHODS: In this prospective study, ESD was performed on five female pigs (weighing 32.4 - 36.8 kg) under general anesthesia using the MASTER. The animals were observed for 2 weeks before being humanely killed for necropsy examination. The main outcome measures were completeness of resection, procedure-related complications, and survival at 2 weeks. RESULTS: The procedure was successfully completed in all five pigs. It took a mean of 21.8 minutes (range 6 - 39 minutes) to complete the ESD of each gastric lesion. All lesions were excised en bloc; the average dimension of the lesions was 77 mm (range 25 - 104 mm). One pig sustained a small intraoperative perforation which was identified and successfully clipped. After completion of the ESD procedures, all pigs survived well for 2 weeks. Necropsy was performed, with intraoperative gastroscopy identifying all the ESD sites as healed. Histopathologic examination showed all ESD sites had healed with partial epithelialization. Microbiological tests of the peritoneal fluid showed only microbes typically found in pigs. CONCLUSION: Performing ESD with MASTER was feasible and safe in this 2-week animal survival study.