Biomarker Of Cellular Aging Research Articles

SENESCENCE DURING IN VITRO EMBRYO DEVELOPMENT IN A MURINE MODEL

The objective of this study seeks to examine markers of senescence and the effect of environmental stressors on murine preimplantation embryos to develop a model to determine whether environmental stress can induce biomarkers of cellular senescence in the developing cells.

Polycystic ovary syndrome and leukocyte telomere length: cross-sectional and longitudinal changes.

ObjectiveTelomeres are DNA–protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular aging. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardiometabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population.DesignThis is a population-based cohort study comprising women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (age 31, n = 190; age 46, n = 207) and referent women (age 31, n = 1054; age 46, n = 1324) with data on LTL.MethodsThe association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age.ResultsWomen with PCOS had similar mean LTL at ages 31 and 46 (P > 0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P = 0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P < 0.001), but not in women with PCOS (P = 0.96).ConclusionsThis finding may suggest a difference in the LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms.

Rational design of near-infrared ratiometric fluorescent probes for real-time tracking of β-galactosidase in vivo

β-Galactosidase (β-gal) is a hydrolytic enzyme in lysosomes and is also an important biomarker of cellular senescence and primary ovarian cancer. Therefore, real-time non-invasive detection of β-gal activity in vivo is of great significance for the prevention of cell senescence and early diagnosis of ovarian cancer. We designed an enzyme-activated proportional near-infrared (NIR) probe (Gal-Br-NO2) for real-time fluorescence quantification and capture of β-gal activity in vivo. The main characteristics of the Gal-Br-NO2 probe include short response time (less than 10 min), large Stokes displacement (155 nm), and near-infrared fluorescence emission (670 nm). The probe has also been successfully used to detect β-gal in ovarian cancer cells and senile cells and can accurately detect endogenous β-gal in zebrafish. Our work provides a potential tool for pre-clinical real-time tracking of β-gal activity in vivo and early diagnosis of disease.

The relation between sensory processing sensitivity and telomere length in adolescents.

BackgroundIn the present study, we investigated the association between sensory processing sensitivity (SPS) and telomere length (TL), which is considered a biomarker of cellular aging. SPS is an individual characteristic describing increased perception and procession of inner or outer stimuli, and is positively related to self‐perceived stress.MethodsWe recruited 82 healthy adolescents aged 13–16 from secondary schools in Germany. SPS was measured with the Highly Sensitive Person Scale, and TL was determined by a multiplex quantitative PCR method.ResultsOur results show that students with higher values of SPS are likely to have shorter telomeres (β = 0.337, p = .001), when adjusting for sex, socioeconomic status, age, and body mass index. These findings are also independent of the negative impact of stress students might have perceived shortly before data collection.ConclusionsOur analysis suggests that students who struggle with low sensory threshold are likely to have shorter telomeres.

Cellular senescence: the good, the bad and the unknown.

Cellular senescence is a ubiquitous process with roles in tissue remodelling, including wound repair and embryogenesis. However, prolonged senescence can be maladaptive, leading to cancer development and age-related diseases. Cellular senescence involves cell-cycle arrest and the release of inflammatory cytokines with autocrine, paracrine and endocrine activities. Senescent cells also exhibit morphological alterations, including flattened cell bodies, vacuolization and granularity in the cytoplasm and abnormal organelles. Several biomarkers of cellular senescence have been identified, including SA-βgal, p16 and p21; however, few markers have high sensitivity and specificity. In addition to driving ageing, senescence of immune and parenchymal cells contributes to the development of a variety of diseases and metabolic disorders. In the kidney, senescence might have beneficial roles during development and recovery from injury, but can also contribute to the progression of acute kidney injury and chronic kidney disease. Therapies that target senescence, including senolytic and senomorphic drugs, stem cell therapies and other interventions, have been shown to extend lifespan and reduce tissue injury in various animal models. Early clinical trials confirm that senotherapeutic approaches could be beneficial in human disease. However, larger clinical trials are needed to translate these approaches to patient care.

Nuclear morphology is a deep learning biomarker of cellular senescence

Cellular senescence is an important factor in aging and many age-related diseases, but understanding its role in health is challenging due to the lack of exclusive or universal markers. Using neural networks, we predict senescence from the nuclear morphology of human fibroblasts with up to 95% accuracy, and investigate murine astrocytes, murine neurons, and fibroblasts with premature aging in culture. After generalizing our approach, the predictor recognizes higher rates of senescence in p21-positive and ethynyl-2’-deoxyuridine (EdU)-negative nuclei in tissues and shows an increasing rate of senescent cells with age in H&E-stained murine liver tissue and human dermal biopsies. Evaluating medical records reveals that higher rates of senescent cells correspond to decreased rates of malignant neoplasms and increased rates of osteoporosis, osteoarthritis, hypertension and cerebral infarction. In sum, we show that morphological alterations of the nucleus can serve as a deep learning predictor of senescence that is applicable across tissues and species and is associated with health outcomes in humans.

Aging-Associated Changes in Oxidative Stress Negatively Impacts the Urinary Bladder Urothelium.

PurposeLower urinary tract symptoms are known to significantly increase with age, negatively impacting quality of life and self-reliance. The urothelium fulfills crucial tasks, serving as a barrier protecting the underlying bladder tissue from the harsh chemical composition of urine, and exhibits signaling properties via the release of mediators within the bladder wall that affect bladder functioning. Aging is associated with detrimental changes in cellular health, in part by increasing oxidative stress in the bladder mucosa, and more specifically the urothelium. This, in turn, may impact urothelial mitochondrial health and bioenergetics.MethodsWe collected mucosal tissue samples from both young (3–4 months old) and aged (25–30 months old) rats. Tissue was evaluated for p21-Arc, nitrotyrosine, and cytochrome C expression by western immunoblotting. Urothelial cells were cultured for single-cell imaging to analyze basal levels of reactive oxygen species and the mitochondrial membrane potential. Mitochondrial bioenergetics and cellular respiration were investigated by the Seahorse assay, and measurements of adenosine triphosphate release were made using the luciferin-luciferase assay.ResultsAging was associated with a significant increase in biomarkers of cellular senescence, oxidative stress, and basal levels of reactive oxygen species. The mitochondrial membrane potential was significantly lower in urothelial cell cultures from aged animals, and cultures from aged animals showed a significant decrease in mitochondrial bioenergetics.ConclusionsAging-related increases in oxidative stress and excessive reactive oxygen species may be contributing factors underlying lower urinary tract symptoms in older adults. The mechanisms outlined in this study could be utilized to identify novel pharmaceutical targets to improve aging-associated bladder dysfunction.

P-571 The newly developed highly sensitive reagent GL13 indicates extensively increased cellular senescence in the follicular fluid of poor responder patients: A prospective observational study

Abstract Study question Do women of diminished ovarian reserve and poor ovarian response (POR) present with increased lipofuscin follicular fluid (FF) levels, indicating increased ovarian cellular senescence? Summary answer Poor responders present with a six-fold increased lipofuscin FF levels indicating extensive senescence in POR ovaries. Lipofuscin may be a new sensitive biomarker for POR. What is known already Lipofuscin is a nondegradable substrate of metabolism accumulating in cells due to impaired mitochondrial/lysosome/proteasome function, upon stress or damage. It is well-documented that lipofuscin constitutes a highly sensitive biomarker of cellular aging and senescence. Recently, a novel reagent (GL13) coupled by a hybrid histochemical–immunohistochemical method were developed for detecting and measuring soluble lipofuscin levels in biological fluids, ascertaining high sensitivity and specificity. Data indicate that lipofuscin levels are associated with oocyte competence and age-related infertility. However, hitherto no data has been published indicating the value of lipofuscin FF levels as a biomarker towards accurately predicting ovarian reserve and response. Study design, size, duration This prospective observational study was collaboratively conducted between November 2020 and September 2021 at the Athens University Medical School and at Genesis Athens Clinic. A total of 32 patients undergoing IVF treatment were enrolled. The study group comprised of 16 POR patients defined according to the Bologna criteria. The control group consisted of 16 normal responder women undergoing IVF due to tubal factor or/and mild male factor infertility. Patients with other infertility aetiologies were excluded. Participants/materials, setting, methods Participants in both groups received the standard short GnRH-antagonist protocol. The FF samples were collected as part of the oocyte retrieval process. Lipid and protein parts of lipofuscin were isolated from FF samples and stained with GL13. The complex of lipofuscin-GL13 was labeled with an anti-biotin HRP conjugated antibody and detected employing a chemiluminescence reaction. Luminescence was measured and signal intensity was corresponding to lipofuscin concentration. Statistical analysis was performed employing R Programming Language. Main results and the role of chance Poor responders presented with a statistically significant six-fold higher lipofuscin FF levels in comparison to the normal responder group (869.21 ± 501.87 vs 146.6 ± 107.64 RLU; P-value &amp;lt;0.0001). Lipofuscin levels were negatively correlated with AFC (Spearman’s Rho: -0.68; P-value &amp;lt;0.0001), AMH levels (Rho: -0.61; P-value =0.0002), estradiol levels on triggering day (Rho: -0.68; P-value &amp;lt;0.0001), number of oocytes retrieved (Rho: -0.54; P-value =0.001), number of mature metaphase II (MII) oocytes obtained (Rho: -0.58; P-value =0.0008), number of normally fertilized (2PN) zygotes (Rho: -0.51; P-value =0.003), number of cleavage stage embryos (Rho: -0.48; P-value =0.005) and number of blastocyst stage embryos (Rho: -0.41; P-value =0.02). These correlations remained statistically significant when adjusting for ovarian stimulation response status. No association was established between Lipofuscin levels and embryo quality neither on Day 3 nor on Day 5. Lipofuscin levels, with a cut-off value at 294, were able to predict ovarian stimulation response status with an area under the curve (AUC) at 0.96. The sensitivity was 0.875, the specificity was 0.938 and the accuracy was 0.906. The positive predictive value was 88.24% and the negative predictive value was 93.33%. Limitations, reasons for caution Limitations of our study refer to the limited size of the studied population, as well as to the lack of data referring to pregnancy outcomes. Moreover, molecular data with regards to the possible mechanisms leading to the observed increased senescence are required. Future studies are needed to verify these findings. Wider implications of the findings Data presented herein indicates, for the first time in literature, that lipofuscin FF levels measured via the GL13 method may be a promising and sensitive tool for predicting POR and stimulation outcome. Lipofuscin could further serve as a valuable novel biomarker indicating ovarian senescence, ovarian reserve status and oocyte competence. Trial registration number Not Applicable

Shorter Telomeres Related to Posttraumatic Stress Disorder Re-experiencing Symptoms in Sexually Assaulted Civilian Women.

Telomeres are short tandem repeats of “TTAGGG” that protect the chromosome ends from deterioration or fusion of chromosomes. Their repeat length shortens with cell division acting as a biomarker of cellular aging. Traumatic stress events during adulthood or childhood have been associated with posttraumatic stress disorder (PTSD) and short leukocyte telomere length (LTL). This study investigated whether LTL was associated with PTSD in a Brazilian sample of sexually assaulted civilian women at two time points: baseline and 1-year follow-up. At baseline, we assessed 64 women with PTSD following sexual assault (cases) and 60 women with no previous history of sexual trauma or mental disorders (healthy controls – HC). At follow-up visit, 13 persistent PTSD cases, 11 HCs, and 11 PTSD remitters patients were evaluated. PTSD diagnosis and severity were assessed using Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders III/IV criteria) and Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), respectively. LTL was measured using multiplex real-time polymerase chain reaction (PCR). In the baseline analysis, we observed that LTL was associated with re-experiencing symptoms (B = −0.16; confidence interval (CI) 95% = −0.027—−0.005; Bonferroni-adjusted p-value = 0.02), but no association was observed between other PTSD symptoms and LTL. In the longitudinal analysis, telomere shortening was no longer observed in patients with PTSD and PTSD remitters. In conclusion, our findings indicate that shorter baseline LTL is associated with early stage of PTSD re-experiencing symptoms in recently sexually assaulted women.

Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies.

Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results. To assess differences in leukocyte telomere length (LTL) in peripheral blood in patients with schizophrenia and related disorders and healthy controls and to explore the effect of potential confounding variables. A search of Ovid MEDLINE, and Proquest databases was conducted to identify appropriate studies published from database inception through December 2020. The review protocol was registered with PROSPERO-ID: CRD42021233280. The initial literature search yielded 192 studies. After study selection in 3 phases, we included 29 samples from 22 studies in the meta-analysis database. We used random effects and meta-regression models to derive Cohen d values with pooled 95% confidence intervals (CI) as estimates of effect size (ES) and to test effects of potential moderators. The overall meta-analysis included 4145 patients with schizophrenia and related disorders and 4184 healthy controls and showed that LTL was significantly shorter in patients, with a small to medium effect size (ES, -0.388; 95% CI, -0.492 to -0.283; p < 0.001). Subgroup meta-analyses did not find a significant effect of age or illness duration on differences in LTL in patients with psychosis relative to controls. Meta-regression analyses showed that none of the putative moderators had a significant effect on effect size estimates. This meta-analysis find further support for the hypothesis of accelerated cellular aging in schizophrenia and related disorders and highlights the need for large longitudinal studies with repeated LTL measurements over time and appropriate assessments of associated factors.

The Comparison of p16 Protein Expression between Single and Multiple Seborrheic Keratosis

Background. Seborrheic keratosis (SK) is a benign epithelial tumor that attacks adults, the elderly, and an increasing number of age-related lesions. Various risk factors influence the pathogenesis of SK, including genetic predisposition and sun exposure. Recently, SK associated with a theory of keratinocytes aging. The aging prevents unlimited and uncontrolled growth of damaged cells, thereby preventing degeneration, but on the other hand, increases the resistance of the cells to apoptosis. From previous studies, the expression of p16 protein increased substantially with age, thus enabling it to be a biomarker of cellular aging at the molecular level. This study was aimed to determine p16 protein expression between single and multiple seborrheic keratoses, the relationship between p16 protein expression in single and multiple SK, and p16 protein expression in the elderly.&#x0D; Methods. Observational study with a cross-sectional design was used to determine the comparison of p16 protein expression between single and multiple seborrheic keratoses was conducted from December 1, 2021, to January 31, 2022. According to the inclusion criteria, study participants with a total of 42 people were selected through the consecutive sampling method. Physical examinations, dermoscopic and histopathologic were carried out until the results were obtained. Then the data were analyzed using the Fisher Test, Chi-Square, with a 95% confidence interval (p &lt;0.05).&#x0D; Results. Most SK patients were found in the age range of 60-69 years (38%), male gender (54.8%), sun-related occasional 3-6 hour per day (50%), location of SK in sun-exposed areas (83.3%), the number of multiple lesions (69%), size 1-2 cm (57.1%), disease duration &gt; 3 years (54.8%), and have no comorbid (69%), an acanthotic subtype of SK (40.5%). All single SK patients have a negative-weak expression of p16 protein (38.2%). Multiple SK patients have a moderate-strong expression of p16 protein (100%) and negative-weak expression of p16 protein (61.8%). Based on statistical analysis using Fisher Exact test has a statistically significant to p16 protein expression with number SK lesion (p-value 0,043).&#x0D; Conclusion. There is a significant correlation between p16 protein expression with single and multiple SK. The study has several limitations. The sample size was small. Other supporting examinations are needed in SK, including polymerase chain reaction (PCR).

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence

BackgroundAcute renal failure due to crush syndrome is one of the leading causes of death in disasters. Ischemic Postconditioning (IPC) is a potentially effective strategy to protect against ischemic reperfusion injury, but a few studies noted its protective effect in crush induced acute kidney injury (AKI). Hence, this study investigated the optimal IPC strategy to prevent crush induced AKI and reveal related cellular mechanisms. MethodsThe right lower extremities of rabbits were constantly compressed for 8 h and then performed five cycles of clamping and releasing the femoral artery and vein before depression using a clip. In terms of the duration of clamping and releasing, the animals were randomly divided into 5 groups, Control, IPC-5sec, IPC-30sec, IPC-1min, and IPC-5min groups; 6 rabbits for each group. Biomarkers of inflammation, renal function, renal tubular injury, and muscular injury, apoptosis, and cellular senescence in kidney were detected. ResultsSix hours after decompression, the levels of Serum Creatine (SCr), Blood Urea Nitrogen (BUN), K+, and Interleukin-6 (IL-6) in IPC-1min and IPC-5min groups were lower than Control, with a statistically significant difference. The morphological study of Periodic Acid-Schiff (PAS) staining demonstrated that 6 h after decompression, IPC-1min can attenuate renal tubular damage renal tubule. Meanwhile, the level of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in circulation in the IPC-30sec, IPC-1min, and IPC-5min groups was significantly decreased compared with the Control group, 2 h after decompression. On the other hand, the levels of serum Creatine Kinase (CK) and Myoglobin (Mb), and the morphological change of muscular damage detected by hematoxylin and eosin (H&E) staining in IPC-1min-treated group were significantly lower than Control group 6 hours after decompression. Further results of the cellular mechanism showed that the apoptotic markers of Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and Caspase3 and the cell senescent markers of senescence-associated β-galactosidase (SA-β-Gal) and nuclear LAMNB1 have changed significantly in the IPC-1min group, compared with the control group. ConclusionsPerforming 5 cycles of 1-min IPC would be a convenient, time-saving, and effective method to prevent crush-induced AKI by attenuating the release of nephrotoxic substances after decompression and downregulation of the expression of apoptosis and cellular senescence biomarkers.

Endogenous pH 6.0 β-Galactosidase Activity Is Linked to Neuronal Differentiation in the Olfactory Epithelium.

The histochemical detection of β-galactosidase enzymatic activity at pH 6.0 (β-gal-pH6) is a widely used biomarker of cellular senescence in aging tissues. This histochemical assay also detects the presence of programmed cell senescence during specific time windows in degenerating structures of vertebrate embryos. However, it has recently been shown that this enzymatic activity is also enhanced in subpopulations of differentiating neurons in the developing central nervous system in vertebrates. The present study addressed the histochemical detection of β-gal-pH6 enzymatic activity in the developing postnatal olfactory epithelium in the mouse. This activity was detected in the intermediate layer of the olfactory epithelium. As development progressed, the band of β-gal-pH6 labeling in this layer increased in width. Immunohistochemistry and lectin histochemistry showed the β-gal-pH6 staining to be strongly correlated with the immunolabeling of the olfactory marker protein (OMP) that identifies mature olfactory sensory neurons. The cell somata of a subpopulation of differentiated olfactory neurons that were recognized with the Dolichos biflorus agglutinin (DBA) were always located inside this band of β-gal-pH6 staining. However, the β-gal-pH6 histochemical signal was always absent from the apical region where the cytokeratin-8 positive supporting cells were located. Furthermore, no β-gal-pH6 staining was found in the basal region of the olfactory epithelium where PCNA/pHisH3 immunoreactive proliferating progenitor cells, GAP43 positive immature neurons, and cytokeratin-5 positive horizontal basal cells were located. Therefore, β-gal-pH6 seems to be linked to neuronal differentiation and cannot be regarded as a biomarker of cellular senescence during olfactory epithelium development in mice.

A 12-Week Yoga-Based Lifestyle Intervention Might Positively Modify Cellular Aging in Indian Obese Individuals: A Randomized-Controlled Trial.

Background: Telomeres and telomerase are considered cardinal biomarkers of cellular aging. Shorter telomeres and low telomerase activity have been associated with obesity and accelerated aging. Objective: To compare the effects of a yoga-based lifestyle intervention (YBLI) with the standard of care (SOC) on cellular aging by estimating telomere length (TL) and telomerase activity in obesity. Design and setting: A parallel, two-arm, randomized-controlled trial was conducted at the Integral Health Clinic, Department of Physiology, All India Institute of Medical Sciences, New Delhi, from March 2017 to October 2019. Participants: Obese (n = 72), body mass index (BMI), 25-35 kg/m2, aged 20-45 years, male (21), and female (51). Intervention: Seventy-two obese participants were randomized to receive either a 12-week SOC (n = 36) or YBLI (n = 36). SOC included management of obesity as per Indian guidelines including a hypocaloric individualized diet and physical activity. The pretested YBLI included asana (physical postures), pranayama (breathing exercises), and meditation. Methods: Blood samples were collected from both the groups at baseline, 2, 4, and 12 weeks. DNA was extracted from peripheral blood mononuclear cells. TL was measured by quantitative PCR, and serum telomerase levels by immunoassay. Outcome measures: Primary outcome measures were the changes in the TL and telomerase levels between the two groups at week 12. Secondary outcome measures were the changes in TL and telomerase, and anthropometric parameters (body weight, BMI, waist-to-hip ratio) at 2, 4, and 12 weeks of intervention in both SOC and YBLI groups. Results: There were no significant changes in TL and telomerase levels between the groups at week 12. The TL was significantly greater in the YBLI group versus the SOC group (p < 0.0001) at 2 weeks. The anthropometric and physiological parameters were influenced positively by both SOC and YBLI. Conclusion: The study did not meet the primary objective, although the results are suggestive of a positive impact of YBLI on aging in obesity as noted within the YBLI group. However, the results should be interpreted carefully, and in the light of other published data. Larger studies to better understand the possible positive benefits of YBLI on cellular aging are recommended. Clinical Trail Registration No. CTRI/2016/08/007136.

Association of Psychological Stress with Telomere Length as a Biomarker of Cellular Aging: A Systematic Review

Association of Psychological Stress with Telomere Length as a Biomarker of Cellular Aging: A Systematic Review

Biomarkers of cellular aging during a controlled human malaria infection

Cellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors. To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model. This approach allowed us to characterize the relationship among cellular aging markers prior, during and post malaria pathophysiology in humans, controlling for infection dose, individual heterogeneity, previous exposure and co-infections. We demonstrate that already low levels of Plasmodium falciparum impact cellular aging by inducing high levels of inflammation and redox-imbalance; and that cellular senescence reversed after treatment and parasite clearance. This study provides insights into the complex relationship of telomere length, cellular senescence, telomerase expression and aging-related processes during a single malaria infection.

Association between body temperature and leukocyte telomere length in Korean middle-aged and older adults.

OBJECTIVESData on associations between body temperature (BT) and leukocyte telomere length (LTL), which has been widely used as a biomarker of cellular senescence in recent epidemiological studies, are limited. Therefore, this study aimed to explore the associations between a normal BT range (35.0-37.5°C) and LTL via 6-year longitudinal observations of 2,004 male and female adults aged 50 or older.METHODSBT was obtained by measuring the tympanic temperature, and relative LTL was determined by real-time polymerase chain reaction. Robust regression analysis was used to evaluate the association between the baseline and follow-up LTL values and their differences.RESULTSA significant inverse association was found between BT and LTL at baseline. The regression coefficient estimate was -0.03 (95% confidence interval, -0.07 to -0.001; p<0.05). This association was stronger in participants with a body mass index >25 kg/m2 and males (p<0.01). However, there were no associations between BT and LTL at follow-up or BT and 6-year longitudinal differences in LTL.CONCLUSIONSThese findings suggest that having a high BT between 35°C and 37.5°C (95°F and 99°F) may be detrimental for obese individuals in terms of biological aging.

Associations of Phthalates and Phenols, Telomere Length, and Breast Cancer in the Long Island Breast Cancer Study Project

BACKGROUND AND AIM: Exposure to phthalates or phenols has been of concern as associated with breast cancer due to the endocrine disrupting effects of these chemicals. Studies related to the modifying role of cellular aging on these associations are lacking. We aim to evaluate the modifying effect of leukocyte telomere length (LTL), a biomarker of cellular aging, on the associations between phthalate and phenol exposure and breast cancer incidence and mortality. METHODS: We used data from 1268 women whose urinary phthalates and phenols and LTL measurements were available from the Long Island Breast Cancer Study Project. Twenty-two metabolites of phthalates and phenols were measured in the spot urine collected from the study participants. The modifying effect of LTL on the association between each individual metabolite and breast cancer incidence and mortality was estimated using interaction terms between LTL and the individual metabolites in logistic regression models and Cox regression models. Odds ratios, hazard ratios, and corresponding 95% confidence intervals (CI) for a one-unit (ln ug/g creatinine) increase of urinary metabolite concentration were estimated at 10th, 50th, and 90th percentiles of LTL. RESULTS:LTL significantly (P0.05) modified the associations between breast cancer incidence and metabolites for eleven phthalates and phenols. Metabolites were, in general, inversely and positively associated with breast cancer incidence at shorter and at longer LTL, respectively. No statistically significant modifying effect was found for LTL in the association between these metabolites and breast cancer mortality. CONCLUSIONS:Women with longer LTL were more susceptible to exposure to phthalates and phenols in the development of breast cancer. But shorter LTL can still increase the detrimental effect of certain types of phenols to breast cancer. KEYWORDS: Phthalate, Phenol, Breast Cancer, Leukocyte Telomere Length

Neighborhood socioeconomic status and biomarkers among participants in the US-based Health Professionals’ Follow-Up Study and Nurses’ Health Study

BACKGROUND AND AIM: Neighborhood socioeconomic status (nSES) may affect human health through stress pathways, but few studies to date have investigated this hypothesis. We studied the association between nSES and multiple biomarkers of cellular aging and inflammation. METHODS: We used data from several nested case-control studies conducted within two US-based cohorts of men and women. Blood samples were collected for a subset of participants ten years after enrollment (1989/90 for NHS, 1996 for HPFS). Relative leukocyte telomere length (rLTL) was assayed using quantitative polymerase chain reaction. Inflammatory biomarkers (c-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR-2)) were assessed. Nine census tract measures of income, home value, earnings from rent and dividends, education, and demographics in 1990 were assigned to each participant’s address (home for NHS, home or work for HPFS) at the time of blood draw. We z-scaled component measures, and then summed together to create a nSES score. Associations between nSES and log-transformed biomarkers were estimated using linear regression models adjusted for individual level demographics, disease history, and lifestyle factors. RESULTS:Participants with available biomarker data ranged from 9,481 (IL-6) to 15,400 (CRP). Women (57.4 years) were younger than men (62.5 years). Adjusted models revealed no association between nSES and rLTL in women (β for 1-unit increase in nSES z-score=0.001, 95% CI: -0.003, 0.005) or men (β=0.001, 95% CI: -0.001, 0.003). However, in women, higher nSES was associated with lower circulating levels of CRP (β=-0.008, 95% CI: -0.013, 0.002), IL-6 (β=-0.006, 95% CI: -0.010, 0.002), and sTNFR-2 (β=-0.002, 95% CI: -0.004, -0.0004). In men, nSES was not associated with CRP, but weaker inverse associations for IL-6 (β=-0.004, 95% CI: -0.010, 0.001) and sTNFR-2 (β=-0.004, 95% CI: -0.006, -0.0013) were observed. CONCLUSIONS:Findings suggest that inflammation, rather than cellular aging, may mediate stress-related consequences of nSES. KEYWORDS: Built environment, internal exposome, socio-economic factors, cancer and cancer-precursors, environmental epidemiology

Symptoms of Prenatal Depression Associated with Shorter Telomeres in Female Placenta.

Background. Depression is a common mood disorder during pregnancy impacting one in every seven women. Children exposed to prenatal depression are more likely to be born at a low birth weight and develop chronic diseases later in life. A proposed hypothesis for this relationship between early exposure to adversity and poor outcomes is accelerated aging. Telomere length has been used as a biomarker of cellular aging. We used high-resolution telomere length analysis to examine the relationship between placental telomere length distributions and maternal mood symptoms in pregnancy. Methods. This study utilised samples from the longitudinal Grown in Wales (GiW) study. Women participating in this study were recruited at their presurgical appointment prior to a term elective caesarean section (ELCS). Women completed the Edinburgh Postnatal Depression Scale (EPDS) and trait subscale of the State-Trait Anxiety Inventory (STAI). Telomere length distributions were generated using single telomere length analysis (STELA) in 109 term placenta (37–42 weeks). Multiple linear regression was performed to examine the relationship between maternally reported symptoms of depression and anxiety at term and mean placental telomere length. Results: Prenatal depression symptoms were significantly negatively associated with XpYp telomere length in female placenta (B = −0.098, p = 0.026, 95% CI −0.184, −0.012). There was no association between maternal depression symptoms and telomere length in male placenta (B = 0.022, p = 0.586, 95% CI −0.059, 0.103). There was no association with anxiety symptoms and telomere length for either sex. Conclusion: Maternal prenatal depression is associated with sex-specific differences in term placental telomeres. Telomere shortening in female placenta may indicate accelerated placental aging.