Effect Of Age Research Articles

The effect of CO2 on the age dependence of neurovascular coupling.

Prior studies have identified variable effects of healthy aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states in healthy controls during cognitive paradigms. 78 healthy participants (18-78 years) underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation) and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) augmented CBv. Peak percentage change in MCAv/PCAv, were compared between CO2 conditions and age groups (< 30, 31-60, and >60 years). For the VS task, in normocapnia, younger adults had a lower NVC response compared to older adults (mean difference (MD): -7.92% (standard deviation (SD): 2.37), p=0.004), but comparable between younger and middle-aged groups. In hypercapnia, both younger (MD: -4.75% (SD: 1.56), p=0.009) and middle (MD: -4.58% (SD: 1.69), p=0.023) age groups had lower NVC responses compared to older adults. Finally, in hypocapnia, both older (MD: 5.92% (SD: 2.21), p=0.025) and middle (MD: 5.44% (SD: 2.27), p=0.049) age groups had greater NVC responses, compared to younger adults. In conclusion, the middle-aged adults demonstrated a variable NVC response, comparable to younger adults under hypercapnia, and older adults under hypocapnia. This may owe to a more cognitively favourable profile while under hypercapnic conditions, compared to hypocapnia.

Are older adults more prosocial than younger adults? A systematic review and meta-analysis.

Prosociality refers to voluntary behaviors that intend to benefit others. Most of the existing literature suggests that older adults tend to act more prosocially compared to younger adults, while some studies show that older adults might not be that prosocial under certain conditions. The current study aimed to summarize the mixed findings and quantify the age difference in prosociality by conducting a qualitative systematic review and a quantitative meta-analysis. Literature search was conducted based on five databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and this review was registered at PROSPERO (CRD42022333373). Based on the qualitative synthesis of 51 studies, older adults (n = 109,911) were more prosocial than younger adults (n = 68,501). The meta-analysis of 46 studies further supported this age effect (Hedges' g = 0.31, 95% confidence interval [0.24, 0.37]), and this age effect might be moderated by the types of prosociality. We discovered a moderate age effect in sharing (Hedges' g = 0.53), but a non-significant age effect in helping (Hedges' g = 0.11), comforting (Hedges' g = -0.20), or mixed prosociality (Hedges' g = 0.15). Additionally, the age effect was only significant when older adults had higher socioeconomic status than younger adults. Future research should develop more comprehensive measures of prosociality, examine more variables that influence aging and prosociality, and investigate the neural mechanism(s) of prosociality to achieve a thorough understanding of the age difference in prosociality.

Differential Aging Effects on Implicit and Explicit Sensorimotor Learning.

Deterioration in motor control is a hallmark of aging, significantly contributing to a decline in quality of life. More controversial is the question of whether and how aging impacts sensorimotor learning. We hypothesized that the inconsistent picture observed in the current literature can be attributed to at least two factors. First, aging studies tend to be underpowered. Second, the learning assays used in these experiments tend to reflect, to varying degrees, the operation of multiple learning processes, making it difficult to make inferences across studies. We took a two-pronged approach to address these issues. We first performed a meta-analysis of the sensorimotor adaptation literature focusing on outcome measures that provide estimates of explicit and implicit components of adaptation. We then conducted two well-powered experiments to re-examine the effect of aging on sensorimotor adaptation, using behavioral tasks designed to isolate explicit and implicit processes. Convergently, both approaches revealed a striking dissociation: Older individuals exhibited a marked impairment in their ability to discover an explicit strategy to counteract a visuomotor perturbation. However, they exhibited enhanced implicit recalibration. We hypothesize that the effect of aging on explicit learning reflects an age-related decline in reasoning and problem solving, and the effect of aging on implicit learning reflects age-related changes in multisensory integration. Taken together, these findings deepen our understanding of the impact of aging on sensorimotor learning.

Hygrothermal effects on ballistic behavior of toughened CFRP laminates

High-speed impact resistance is a critical consideration in the design and assessment of composites for aerospace applications during their service life, especially in the context of hygrothermal aging. This study, combining experiment and numerical simulation, investigates hygrothermal effects on the high-speed impact performance of a toughened T700/EH301 carbon/epoxy composite material. Three distinct hygrothermal conditions, namely Unaged, Aged, and Redried, are investigated. Experimental results reveal an apparent improvement in ballistic limit after hygrothermal aging (170.2 m/s, a notable increase of 11.2%), still maintaining an excellent performance even after redrying (158.5 m/s, an increase of 3.2%). Inspired by the micrographic analysis, a high-fidelity finite element model, referred to as HFEDCM (High Fidelity Explicit Discrete Crack Model), has been developed. This model not only explains the positive effects of hygrothermal aging on high-speed impact performance but also accurately captures the macroscopic damage morphology of composite laminates. It has been quantitatively and qualitatively demonstrated that the enhancement of the fracture toughness of the “fiber bundle” plays a critical role in improving the high-speed impact resistance of composites under hygrothermal aging.

Exposure of small ruminants to the Schmallenberg arbovirus in Germany from 2017 to 2018 – animal-specific and flock-management-related risk factors

The Schmallenberg virus (SBV), an emerging Orthobunyavirus of mainly ruminant hosts, caused a substantial epidemic in European ruminant populations between 2011 and 2013. The pathogen is transmitted by arthropod vectors (Culicoides spp.) and can cause reproductive disorders and severe malformations of the offspring or stillbirth. The present study aimed to assess SBV seroprevalence among German sheep and goats a few years after the first virus detection in the country (November 2011). In addition, an extensive risk factor analysis including host-specific and husbandry-related factors was implemented. Seroprevalence was determined by examining serum samples from 2759 sheep and 446 goats out of a total of 70 flocks across five German federal states. The samples were withdrawn in the period between 2017 and 2018. Using a commercial competitive ELISA, antibodies against SBV were detected in all 70 investigated flocks. A percentage of 60.1 % (1657/2759) of the sheep and 40.4 % (180/446) of the goat sera contained SBV antibodies. Generalized linear mixed modeling revealed significant effects of host species (sheep > goats), age (old > young) and sex (female > male) on SBV seroprevalence. For both species, also the farming purpose, and for goats, ectoparasite treatment and the presence of cattle on the farm played a role in terms of risk for SBV exposure. The observations from this study still emphasize a wide distribution of the pathogen in Germany. Nevertheless, the observed seroprevalence might not be sufficient to achieve effective herd immunity. Pinpointing risk factors identified susceptible populations for targeted vaccination programs to reduce potential animal losses caused by SBV.

The chromatin accessibility and transcriptomic landscape of the aging mice cochlea and the identification of potential functional super-enhancers in age-related hearing loss

BackgroundPresbycusis, also referred to as age-related hearing loss (ARHL), is a condition that results from the cumulative effects of aging on an individual's auditory capabilities. Given the limited understanding of epigenetic mechanisms in ARHL, our research focuses on alterations in chromatin-accessible regions.MethodsWe employed assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) in conjunction with unique identifier (UID) mRNA-seq between young and aging cochleae, and conducted integrated analysis as well as motif/TF-gene prediction. Additionally, the essential role of super-enhancers (SEs) in the development of ARHL was identified by comparative analysis to previous research. Meanwhile, an ARHL mouse model and an aging mimic hair cell (HC) model were established with a comprehensive identification of senescence phenotypes to access the role of SEs in ARHL progression.ResultsThe control cochlear tissue exhibited greater chromatin accessibility than cochlear tissue affected by ARHL. Furthermore, the levels of histone 3 lysine 27 acetylation were significantly depressed in both aging cochlea and aging mimic HEI-OC1 cells, highlighting the essential role of SEs in the development of ARHL. The potential senescence-associated super-enhancers (SASEs) of ARHL were identified, most of which exhibited decreased chromatin accessibility. The majority of genes related to the SASEs showed obvious decreases in mRNA expression level in aging HCs and was noticeably altered following treatment with JQ1 (a commonly used SE inhibitor).ConclusionThe chromatin accessibility in control cochlear tissue was higher than that in cochlear tissue affected by ARHL. Potential SEs involved in ARHL were identified, which might provide a basis for future therapeutics targeting SASEs related to ARHL.

Locus coeruleus contrast and diffusivity metrics differentially relate to age and memory performance

Neurocognitive aging researchers are increasingly focused on the locus coeruleus, a neuromodulatory brainstem structure that degrades with age. With this rapid growth, the field will benefit from consensus regarding which magnetic resonance imaging (MRI) metrics of locus coeruleus structure are most sensitive to age and cognition. To address this need, the current study acquired magnetization transfer- and diffusion-weighted MRI images in younger and older adults who also completed a free recall memory task. Results revealed significantly larger differences between younger and older adults for maximum than average magnetization transfer-weighted contrast (MTC), axial than mean or radial single-tensor diffusivity (DTI), and free than restricted multi-compartment diffusion (NODDI) metrics in the locus coeruleus; with maximum MTC being the best predictor of age group. Age effects for all imaging modalities interacted with sex, with larger age group differences in males than females for MTC and NODDI metrics. Age group differences also varied across locus coeruleus subdivision for DTI and NODDI metrics, and across locus coeruleus hemispheres for MTC. Within older adults, however, there were no significant effects of age on MTC or DTI metrics, only an interaction between age and sex for free diffusion. Finally, independent of age and sex, higher restricted diffusion in the locus coeruleus was significantly related to better (lower) recall variability, but not mean recall. Whereas MTC has been widely used in the literature, our comparison between the average and maximum MTC metrics, inclusion of DTI and NODDI metrics, and breakdowns by locus coeruleus subdivision and hemisphere make important and novel contributions to our understanding of the aging of locus coeruleus structure.

Health-related quality of life profile of newly diagnosed patients with Hodgkin and non-Hodgkin lymphomas: A real-world study including 3922 patients from the French REALYSA cohort

IntroductionConsidering the notable advances made in the treatment of lymphoma, assessment of health-related quality of life (HRQoL) of lymphoma patients has become a critical aspect to consider both in clinical research and routine practice. However, there is paucity of information about lymphoma specific HRQoL profile at diagnosis. Patients and methodsHRQoL at diagnosis was assessed for 3922 adult patients with newly diagnosed high-grade (HG) (n = 1994), low-grade (LG) (n = 1053) non-Hodgkin (NHL) and Hodgkin (HL) (n = 875) lymphomas included in REal world dAta in LYmphoma and Survival in Adults (REALYSA, NCT03869619), a prospective non-interventional multicentric cohort in France. Disease-specific HRQoL aspects were assessed with three validated EORTC questionnaires, namely, the QLQ‐NHL‐HG29, the QLQ-NHL-LG20 and the QLQ-HL27, for patients with NHL-HG, NHL-LG and HL, respectively. ResultsWe confirmed the high-level of completion of these questionnaires in REALYSA cohort, ranging from 84 % for QLQ-HG29 to 88 % for QLQ-HL27. The proportion of patients with impaired global health status was as follows: T-cell NHL, 67 %; diffuse large B-cell (DLBCL), 62 %; Burkitt, 61 %; HL, 53 %; marginal zone, 49 %; mantle cell, 48 %; follicular, 47 %. Multivariable regression analyses for DLBCL, follicular and HL showed that gender, performance status and B symptoms were independently associated with all HRQoL dimensions. However, a variable effect of age and stage were observed among these three subtypes. ConclusionsA comprehensive analysis was made describing the HRQoL profile of newly diagnosed patients with different types of lymphomas. Our data may help to enhance the interpretation of HRQoL results in future studies using the recently validated EORTC lymphoma specific questionnaires.

P-755 Effect of female age and specific cycle characteristics on success in modified natural frozen-thawed single euploid embryo transfer cycles (mNC/FET)

Abstract Study question Does the age of woman and specific cycle characteristics impact the success of modified natural frozen-thawed single euploid embryo transfer cycles (mNC/FET)? Summary answer The success rate of mNC/FET cycles is similar in all age groups. As the LH level increased ( above 23.5ng/dL) the success was significantly increased. What is known already The success of frozen embryo transfer can depend on various factors such as the patient’s age, the number of transferred embryos, the duration of embryo culture, and the method used to prepare the endometrium (Holschbach et al. 2023). However, there is currently insufficient evidence in the literature about the effect of age and cycle characteristics on the effectiveness of mNC/FET cycles in patients who have received single top and good quality euploid embryos. Study design, size, duration This study, conducted at Istanbul Memorial Hospital, ART and Reproductive Genetics Center, is a retrospective, single-centre analysis of 583 cycles of euploid mNC/FET in women aged 22-44 years. The study period was from July 2017 to January 2024. The cycles were divided into two groups based on the age of the women. Group A (n = 408) included women under the age of 38, while Group B (n = 175) included women aged 38 or above. Participants/materials, setting, methods The study investigated success predictors in mNC/FET with top and good-quality embryos. Excluded were women with recurrent pregnancy losses, recurrent implantation failure, high BMI (&amp;gt;35kg/m2), uterine/endometrial problems, severe male infertility, and autoimmune diseases. The mNC/FET success was a pregnancy lasting 12 weeks or more. The analysis included patient demographics and cycle outcomes. Chi-square, t-tests, and Mann-Whitney U tests assessed variables with a p-value &amp;lt; 0.005, indicating statistical significance. Main results and the role of chance No significant demographic differences were observed between the two groups, except for AMH levels. AMH levels were significantly higher in younger group than older group (3.02 ng/ml vs. 1.96 ng/ml, p = 0.000). The mNC/FET success rates were similar, with 76% in the younger group and 73% in the older group. Estradiol levels the day before trigger day were significantly higher in older group (278.02 pg/ml vs. 237.84pg/ml, p = 0.028). Both groups had similar mean LH levels (32.50 IU/L and 32.41 IU/L, respectively), estradiol levels and endometrial thickness on the trigger day. In the younger group, LH rise was observed later, follicular phase was longer, and embryo transfer day was later than the older group (p = 0.001). Univariate regression analysis revealed that increased LH level was an important independent variable in achieving mNC/FET success, with a 1.001-fold increase (p = 0.043). The LH levels of 23.5 IU/L or higher predicted high mNC/FET success with 60% sensitivity and 43% specificity based on the Receiver Operating Characteristic curve. (AUC: 0.606, %95 CI 0.540-0.671, p = 0.002). Prolonged infertility duration and previous ET failures reduced mNC/FET success by 0.889 and 0.544-fold, respectively (p = 0.002, p &amp;lt; 0.001). Higher β-hCG levels on days 14 and 16 increased mNC/FET success by 1.038-fold and 1.008-fold, respectively (p &amp;lt; 0.001). Limitations, reasons for caution Our study has limitations as it was retrospective. Prospective randomized studies are needed to evaluate the differences between the young (age &amp;lt;38) and old patient groups (age ≥38) based on mNC/FET success. The association between LH rise and mNC/FET success needs verification with a larger sample. Wider implications of the findings The mNC/FET success rates are similar in young (age &amp;lt;38) and old patient groups (age ≥38). However, prolonged infertility duration and previous failed ET cycles decreased the success of mNC/FET. Additionally, It is important to schedule trigger time after the optimum LH rise, which is 23.5 IU/L or higher. Trial registration number not applicable

Neuropsychiatric symptom burden in early-onset and late-onset Alzheimer's disease as a function of age.

We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n=2433; late-CU, n=6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. Presence (ps<0.0001) and severity (ps<0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps<0.05) and nighttime behaviors more frequent and severe in LOAD (ps<0.05). Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.

O-013 Population pharmacokinetics of follitropin delta during ovarian stimulation

Abstract Study question Which patient characteristics affect serum follicle stimulating hormone (FSH) concentrations in women undergoing ovarian stimulation (OS) with follitropin delta, a human cell line derived FSH? Summary answer Body weight is the main determinant of serum FSH concentrations during OS. Renal function, race, ethnicity, hepatic function and age have at most small influence. What is known already The pharmacokinetics of FSH have been studied in dedicated studies with serial blood sampling, typically conducted in healthy subjects. Such studies are designed to provide detailed pharmacokinetic profile information but lack the statistical power for identifying individual patient characteristics affecting FSH exposure. Population pharmacokinetic modelling enables evaluating the influence of patient characteristics based on few FSH measurements per patient if data from many patients are available. Study design, size, duration Serum FSH concentrations were assessed by immunoassay in seven randomized, controlled, blinded, multicentre trials of follitropin delta in women undergoing an assisted reproductive technology program. The trials were conducted in the United States, Canada, Europe, Brazil, and Asia. In all, 2,721 women treated with follitropin delta contributed to the evaluation with 6,952 FSH measurements. Participants/materials, setting, methods FSH concentrations were described with a pre-specified one-compartment population pharmacokinetic model. The key model parameters were the apparent total clearance (CL/F) of follitropin delta, the interindividual variability in CL/F and the effects of baseline values of body weight, age, race, ethnicity, renal and hepatic function on CL/F. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and hepatic function by alanine transaminase (ALT) and bilirubin levels. Main results and the role of chance Area under the FSH concentration-time curve during a dosing interval (AUC) was derived from dose and CL/F. Body weight had the most pronounced effect on AUC, both in terms of effect magnitude and statistical significance. AUC was 1.28-fold higher (90% confidence limits: 1.25; 1.30) in women with a body weight of 47 kg (5th percentile) compared to women with a median body weight of 62 kg. The effect estimates of eGFR, Asian race and Black race on CL/F were within the bioequivalence limits of 0.80 and 1.25, but with 90% confidence limits not including a value of 1. The effect of Black race was estimated to be a 1.19 fold (90% confidence limits: 1.12; 1.26) higher AUC, as compared to White race. Despite this, the individual estimates of AUC were close to identical comparing these patient populations (mean (SD) relative to a typical study participant: 1.00 (0.25) and 0.97 (0.23), respectively). This is likely due to the mean body weight being higher in Black trial participants compared to White trial participants (78.3 kg compared to 68.2 kg). The effects of age, ethnicity and the hepatic function markers ALT and bilirubin were well within the bioequivalence range of 0.80 – 1.25. Limitations, reasons for caution Potential effects of subject characteristics on PK parameters such as subcutaneous absorption rate or volume of distribution could not be evaluated due to the number of serum FSH concentration measurements available per patient. Wider implications of the findings After follitropin delta administration, serum FSH concentrations are inversely related to body weight; this may be helpful for determining whether there is a need to consider body weight when selecting dose. Trial registration number NCT01426386, NCT02309671, NCT01956110, NCT03228680, NCT03296527, NCT03740737, NCT03738618, NCT03809429

P-054 Paternal age and cryopreservation impact sperm chromatin status as indicated by changes in protamine and histone levels

Abstract Study question Do paternal age and cryopreservation alter sperm chromatin status in normospermic men? Summary answer Paternal age and cryopreservation appear to impact sperm chromatin condensation by altering protamine and histone DNA levels. What is known already Semen parameters do not accurately reflect male fertility and thus are not adequate to assess the impact of patient profile and semen manipulation/conservation on sperm functional quality. DNA protamination leads to sperm chromatin condensation, which is associated with sperm maturity but also appears to function as a defence mechanism against oxidative attack. In the face of contrasting/insufficient previous data, the impact of advanced paternal age (APA) and cryopreservation on sperm chromatin condensation and histone/protamine balance remains unclear. Study design, size, duration Twenty-two normospermic men, 11 of which with advanced paternal age (APA; ≥42) and 11 pre-APA (≤35), provided semen samples by masturbation (1-5 days abstinence). Fresh and cryopreserved/thawed samples from all patients were assessed for chromatin histone staining, while samples from a subgroup of 10 patients (5 pre-APA and 5 APA) were assessed for protamine presence. The effects of age and cryopreservation on the percentage of stained cells were assessed with the Fisher’s exact test. Participants/materials, setting, methods Semen samples were provided by male partners of couples treated at our fertility centre. Sample aliquots were cryopreserved and analyzed after thawing (CryoSperm &amp; Sperm Preparation Medium, Origio). Histone presence was assessed through aniline blue staining and protamine presence was indirectly assessed through staining with the protamine competitor Chromomycin A3 (CMA3); stained cells were visualized by bright field and fluorescence microscopy, respectively. Two hundred sperm cells were evaluated in each sample by the same embryologist. Main results and the role of chance Mean paternal age was 31.5±3.9 and 44.4±2.1 years for pre-APA and APA patient-groups, respectively. Major parameters observed in fresh semen samples were: 2.3±0.7 vs. 3.6±1.6mL (volume); 39±28 vs. 38±12 x10ˆ6/mL (concentration); 7±12 vs. 6±5% (rapid progressive motility); 41±12 vs. 38±13% (slow progressive motility); 12±5 vs. 11±4% (non-progressive motility); 40±17 vs. 45±16% (immotile) and 5±1 vs. 6±2% (normal morphology), for pre-APA and APA, respectively. The percentage of aniline blue (histone marker) positive cells was less than half in fresh samples from APA as compared to pre-APA patients (10.2% and 23.4%, respectively, p &amp;lt; 0.0001). Consistently, the percentage of CMA3 (protamine absence marker) positive cells was less than half in APA as compared to pre-APA patients (6.4% and 16.4%, respectively, p &amp;lt; 0.0001). In both age groups, the percentages of aniline blue and CMA3 positive cells were higher in cryopreserved/thawed samples as compared to their fresh counterparts (aniline blue positive: 35.2% vs. 23.4% and 22.0% vs. 10.2%; CMA3 positive: 27.2% vs. 16.4% and 18.8% vs. 6.4%, in cryopreserved vs. fresh in pre-APA and APA, respectively, p &amp;lt; 0.0001). Limitations, reasons for caution Our study is limited by the potential interference of confounding factors not equally distributed in age groups. The conclusions from this study must be confirmed in other patient populations with different race/genetics and habits. Wider implications of the findings Our findings suggest that APA increases, while cryopreservation decreases, sperm chromatin condensation, as indicated by changes in DNA histone and protamine abundance. Our study thus sheds light on the impact of paternal age and cryopreservation on sperm quality, providing new valuable parameters for reproductive medicine practice and research. Trial registration number na

Expression and secretion of SPARC, FGF-21 and DCN in bovine muscle cells: Effects of age and differentiation.

Skeletal muscle growth is an economically important trait in the cattle industry. Secreted muscle-derived proteins, referred to as myokines, have important roles in regulating the growth, metabolism, and health of skeletal muscle in human and biomedical research models. Accumulating evidence supports the importance of myokines in skeletal muscle and whole-body health, though little is known about the potential presence and functional significance of these proteins in cattle. This study evaluates and confirms that secreted proteins acidic and rich in cysteine (SPARC), fibroblast growth factor 21 (FGF-21), myostatin (MSTN), and decorin (DCN) are expressed and SPARC, FGF-21, and DCN are secreted by primary bovine satellite cells from 3- (BSC3; n = 3) and 11- (BSC11; n = 3) month -old commercial angus steers. Cells were cultured and collected at zero, 12, 24, and 48 hours to characterize temporal expression and secretion from undifferentiated and differentiated cells. The expression of SPARC was higher in the undifferentiated (p = 0.04) and differentiated (p = 0.07) BSC11 than BSC3. The same was observed with protein secretion from undifferentiated (p <0.0001) BSC11 compared to BSC3. Protein secretion of FGF-21 was higher in undifferentiated BSC11 (p < 0.0001) vs. BSC3. DCN expression was higher in differentiated BSC11 (p = 0.006) vs. BSC3. Comparing undifferentiated vs. differentiated BSC, MSTN expression was higher in differentiated BSC3 (p ≤ 0.001) for 0, 12, and 24 hours and in BSC11 (p ≤ 0.03) for 0, 12, 24, and 48 hours. There is also a change over time for SPARC expression (p ≤ 0.03) in undifferentiated and differentiated BSC and protein secretion (p < 0.0001) in undifferentiated BSC, as well as FGF-21 expression (p = 0.007) in differentiated BSC. This study confirms SPARC, FGF-21, and DCN are secreted, and SPARC, FGF-21, MSTN, and DCN are expressed in primary bovine muscle cells with age and temporal differences.

P-397 A retrospective analysis shows a high effect in reproductive outcomes as age increases associated to endometrial factor in IVF advanced maternal age (AMA) patients

Abstract Study question Is there an increasing risk of a negative reproductive outcomes with every passing year associated with endometrial factor in AMA patients? Summary answer The risk of implantation failure and pregnancy loss associated with endometrial factor increase in 2.0% and 1.2% respectively with each passing year in AMA patients. What is known already Nowadays, there is a delay in maternity due to lifestyle, leading to a progressive increase in the age of women at the first childbirth increasing infertility. However, no universal definition of AMA has been established yet. Typically, studies are performed between different groups of age, establishing arbitrary thresholds. Besides, studies about AMA infertility mainly focus on the decline in oocyte quality, but the effects of age on the endometrium are often overlooked. Therefore, there is a lack of studies centered on endometrial factor and considering age year-by-year to be able to strictly establish when fertility decline starts and its magnitude. Study design, size, duration This retrospective study included a total of 33,735 single embryo transfers from 21,506 IVF AMA patients (&amp;gt;35 y.o, BMI 19-25 kg/m2) performed with high quality embryos (embryos from donated oocytes (donor &amp;lt;35 y.o) or euploid embryos from their own oocyte cohort) transferred in day 5 in an endometrial Hormonal Replacement Therapy (HRT) cycle. Evaluated transfers were performed between 2001 and 2022 in 19 clinics in Spain. This study was approved by an IRB (2203-FIVI-030-PD). Participants/materials, setting, methods A logistic regression analysis was performed, considering the patient’s age (42.93±3.45 y.o.) as a continuous and dependent variable and the reproductive outcome as an independent variable. The risk of obtaining a negative pregnancy outcome was estimated as risk ratios at a 95% confidence interval. A p-value&amp;lt;0.05 was considered as statistically significant. Reproductive rates (live birth and pregnancy loss) were calculated and compared each passing year in the studied range of ages (35-51 y.o). Main results and the role of chance The rates of live birth, Implantation failure and pregnancy loss associated to endometrial factor were affected as age increased in IVF AMA patients (&amp;gt;35 y.o). The implantation failure risk was increased in each passing year a 2% (Risk Ratio (RR) = 1.020 (1.003, 1.021) 95% confidence interval (95%CI), p-value=6.0E-09) and pregnancy loss risk was increased in each passing year a 1.2% (RR = 1.012, (1.003, 1.021) 95%CI, p-value=0.0096). Live birth rate decreased progressively from 42% observed in 35 y.o. to 32% in 50 y.o. Nevertheless, the pregnancy loss rate increased progressively from 29% in 35 y.o. to 37% in 50 y.o. Moreover, results shown a more drastic decrease of implantation failure rate after 42 years old and a pregnancy loss rate after 45 years old. Limitations, reasons for caution Only transfers from Spanish population under a HRT cycle were included, decreasing the results variability. However, the results could not be generalized to other hormonal cycles. Moreover, biochemical and clinical pregnancy loss could not be distinguished in this study considering pregnancy loss as a term that includes both of them. Wider implications of the findings To our knowledge, this is the first study in which the endometrial factor in AMA patients was analyzed year by year, helping to define in a more reliable way the ages at which the sharpest changes occur to improve clinical practices on endometrial implantation failure in AMA patients. Trial registration number Not applicable

P-711 Female age at embryo creation and embryo transfer do not impact the ongoing pregnancy rates in single euploid frozen embryo transfers

Abstract Study question Which factors influence the ongoing pregnancy rate in single euploid frozen embryo transfer (seFET) cycles? Summary answer Ongoing pregnancy rates in seFET cycles are significantly influenced by parity, BMI, embryo quality, trophectoderm biopsy day and endometrial preparation, but not by female age. What is known already The probability of a pregnancy is influenced by several factors and female age is the major determinant as the ovarian reserve decreases and embryo aneuploidy increases with age. Preimplantation genetic testing for aneuploidy and embryo selection was considered to mitigate the effect of female age on ART treatment outcomes by selecting euploid embryo(s) for embryo transfer (ET). Previously published data point to a decline in pregnancy rates with increased maternal age even when a euploid embryo is transferred. However, other factors besides embryo ploidy might play a role in the chance of achieving an ongoing pregnancy. Study design, size, duration Retrospective study, including 1923 women who underwent a seFET between 04/2017 and 08/2023. Patients’ (age at oocyte-pick-up and seFET, BMI, parity, endometrial preparation type) and embryo characteristics (Day of biopsy, embryo quality (EQ)) were considered for the analysis. Ongoing pregnancy was defined as viable pregnancy beyond 12 weeks of gestation. Participants/materials, setting, methods Women, undergoing a seFET either in a true natural cycle (NC) t or in a hormonal replacement cycle (HRT). Only cycles with embryos being biopsied on day 5 or day 6 and a known outcome of the cycle were included. Main results and the role of chance There were 990 (51.48%) ongoing pregnancies among 1923 included transfers. The ongoing pregnancy rates were 51.8%, 47.4%, 52.3% and 52.8% for women aged ≤35, &amp;gt;35 to ≤ 37, &amp;gt;37 to ≤ 40, and &amp;gt;40 years-old at seFET, respectively. Cochrane Armitage test did not show a significant trend for decreasing pregnancy rates with increasing female age at OPU (P = 0.679) or at transfer (P = 0.609). Multivariable regression analyses showed primiparous, and multiparous women were more likely to have an ongoing pregnancy compared to nulliparous women (OR: 2.96, 95%CI:2.22-3.94 and 2.73, 95%CI:2.10-3.55, respectively, P &amp;lt; 0.001 for both) and those who had a natural endometrial preparation (OR: 1.53, 95%CI: 1.24-1.88, P &amp;lt; 0.001). Transfers with good quality embryo had higher ongoing pregnancy rates compared to those who had a fair quality embryo (OR: 2.0, 95%CI: 1.37-2.91, P &amp;lt; 0.001). Being overweight or obese at the time of transfer were associated with lower ongoing pregnancy rates compared to normal weight (OR: 0.71, 95%CI: 0.56-0.89, and 0.68, 95%CI: 0.52-0.88, respectively, P = 0.003 for both). Age categories at the time of transfer did not show a significant effect on ongoing pregnancy rates in multivariable analyses (P &amp;gt; 0.05 for all) and there was no significant interaction between age at OPU and embryo quality categories either (P = 0.881 and 0.601). Limitations, reasons for caution The retrospective design of the study is a limitation. Wider implications of the findings This analysis did not confirm the otherwise reported negative impact of female age on the outcome of seFET cycles. Outcomes are significantly influenced by BMI, parity, EQ-related factors as well as the endometrial preparation. As BMI and endometrial preparation can be influenced, the adequate choice might improve seFET outcomes. Trial registration number not applicable

P-535 Effect of advanced female age (AFA) on the ratio of patients receiving mosaic embryo transfers

Abstract Study question How does female age affect ratio of patients with at least one euploid embryo (≥1EE) and at least one mosaic embryo without any euploid ones(≥1ME)? Summary answer Percentage of patients receiving mosaic embryo transfers increases with female age. What is known already Introduction of Next Generation Sequencing (NGS) to the area of Preimplantation Genetic Testing for Aneuploidy (PGT-A) has enabled detection of mosaicism in human embryos. Studies reporting the birth of healthy babies after the transfer of embryos with a chromosomal mosaic result on PGT-A have been published (Greco et al., 2015; Kahraman et al., 2020; Viotti et al., 2021 and 2023). Data suggested lower implantation rates and higher miscarriage rates when mosaics were compared with euploid embryo transfers. The percentage of mosaic embryos in overall tested embryos decreases with increased maternal age, similar to euploid embryos’ decline (Sanders et al., 2023). Study design, size, duration This retrospective study includes 7287 cycles with PGT-A performed between January 2017 and December 2023. Number of biopsied blastocysts was 21,277 and all were tested with NGS. All PGT-A testing was conducted on Ion Torrent S5 (Thermo Fisher Scientific) according to the manufacturer guidelines. The mosaic embryo reporting thresholds were determined as 20 to 80%. Participants/materials, setting, methods Euploidy ratio (ER) was defined as (euploid embryos (n)/ all tested embryos(n)). Mosaicism ratio (MR) was defined as (mosaic embryos (n)/all tested embryos(n)). Alternative mosaicism ratio (AMR) was defined as the number of mosaic embryos divided by the sum of euploid embryos and mosaic embryos. In other words, AMR can be defined as the number of mosaic embryos divided by non-aneuploid embryos. Female ages were divided into five categories: FAG1:&amp;lt;35, FAG2:35-37, FAG3:38-40, FAG4:41-42, FAG5:&amp;gt;42. Main results and the role of chance The number of cycles, total number and average biopsied embryos with standard deviations were highest in FA1 and declined with AFA: FAG1:2537, 9298, 3.7±2.2; FAG2:1348, 4140, 3.1±1.7; FAG3:1701, 4298, 2.5±1.6; FAG4: 958,2116, 2.2±1.5; FAG5:738, 2407, 1.9±1.2. ER and MR were observed to decrease with AFA: FAG1:%48.4, %15.2; FAG2:%39.0, %12.7; FAG3:%26.5, %10.5; FAG4:%14.9, %6.0; FAG5:%5.0, %2.6. This decrease was statistically significant (p &amp;lt; 0.0001, Chi-Square Test). However, when AMR was calculated among age groups, AMR was increasing with AFA: FAG1:%23.9; FAG2:%24.6; FAG3:%28.5;FAG4:%28.7; FAG5:%34.5 and this was also statistically significant (p = 0.0002, Chi-Square Test). Correlation of MR and AMR with female age groups were tested with Pearson correlation coefficient and MR was found to be negatively correlated with AFA whereas AMR was positively correlated (r=-0.19, p &amp;lt; 0.0001; r = 0.07, p &amp;lt; 0.0001, respectively). The ratio of patients with ≥1EE and ≥1ME was found to be decreasing with AFA when compared to overall tested cycles: FAG1: %83%, %7; FAG2: %69, %9; FAG3: %47, %11; FAG4: %28, %9; FAG5: %9, %4. However, the ratio of ≥ 1ME in cycles with transferrable embryos significantly increased with AFA consisting of more than one fourth of embryo transfer cycles above 38 years of age: FAG1: %7; FAG2: %12; FAG3: %19; FAG4: %24; FAG5: 31%. Limitations, reasons for caution These are the results of a single ART and Reproductive Genetics Center with its strictly defined standard operating procedures for PGT-A testing and ovarian stimulation protocols. Although not expected, different PGT-A testing methodologies or stimulation protocols may influence the above-mentioned outcomes. Wider implications of the findings The alternative mosaicism ratio defined here is generally overlooked but impacts the treatment strategies of ART patients, specifically for the advanced maternal age groups. Trial registration number not applicable

O-089 Association of pituitary suppression method with euploid blastocyst yield in preimplantation genetic testing for aneuploidy (PGT-A) cycles

Abstract Study question Do progestin primed ovarian stimulation (PPOS) cycles have lower euploidy yield compared to pituitary suppression with gonadotropin releasing hormone (GnRH) antagonists? Summary answer The choice of pituitary suppression method has no bearing on euploid retrieval per blastocyst tested. What is known already Progestin primed ovarian stimulation cycles are an alternative to GnRH antagonists when fresh embryo transfer is not a priority. While the two approaches have been shown to be similar in terms of conventional stimulation outcomes such as mature oocyte retrieval, and blastulation rates, there is still some lingering controversy regarding cumulative pregnancy rates and the effects of progestins on embryo genetic constitution. Study design, size, duration This was a multicenter retrospective cohort study including data from two tertiary-level treatment centers. Participants/materials, setting, methods Infertile women undergoing ovarian stimulation with either progestin primed or GnRH antagonist pituitary suppression with the intention of transfer after PGT-A embryo testing with next-generation sequencing. The main outcome parameter was euploid embryo count per blastocyst tested and was modeled with mixed-effects log-binomial regression models. Results were adjusted for patient age and laboratory performing the PGT-A tests while they were not adjusted for embryo quality to avoid collider bias. Main results and the role of chance A total of 1425 PGT-A tested blastocysts from 383 cycles of 365 patients were included in the analysis. 243 cycles (63.4%) received GnRH antagonists for pituitary suppression while 140 (36.5%) received progestins. The overall euploidy rates per blastocyst tested in the GnRH antagonist and PPOS groups were 38.8% vs. 31.1%, 30.2% vs. 29.4%, 27.0% vs. 25.2%, and 13.8% vs. 14.5% for the age categories &amp;lt;35, 35-37, 38-40, and &amp;gt;40, respectively. After adjusting for the effect of female age at testing and the laboratory performing the PGT-A test, the type of pituitary suppression was not significantly associated with euploid retrieval per blastocyst tested (adjusted risk ratio: 0.94, 95% CI: 0.70 - 1.28, P = 0.701). After testing, 191 women received 233 embryo transfers. Human chorionic gonadotropin (hCG) positivity per transferred embryo was not significantly different between progestin primed and GnRH antagonist cycles (RR: 0.89, 95% CI: 0.71 – 1.08, P = 0.268). Limitations, reasons for caution This is a retrospective study with data from multiple centers with a non-standardized selection of blastocysts to be tested. In addition, the sample size and retrospective nature of the data may have biased the estimates. Wider implications of the findings The choice of pituitary suppression method does not appear to have a significant effect on euploid embryo retrieval rates or hCG positivity per transfer. The choice of medication can be based on the needs of the individual case without concern for suboptimal PGT-A outcomes. Trial registration number Not Applicable

O-070 Cas9-based chromosome labelling reveals large-scale age-dependent centromere reorganisation in human oocytes

Abstract Study question Can centromeres be labelled in live human oocytes using Cas9 system and is the labelling efficiency affected by advancing female age? Summary answer Centromeres in human oocytes can be labelled using Cas9 system. Signal intensity decreases in oocytes from older patients, suggesting centromeric DNA unravelling as oocytes age. What is known already Aneuploidy in human oocytes is associated with infertility, pregnancy loss or genetic diseases in offspring. It arises due to abnormal chromosome segregation during meiosis, with the risk increasing with advancing female age. This is attributed to age-dependent loss of pericentromere-localised cohesion which holds sister chromatids together. Our work revealed that shugoshin-2 (Sgo2), a protein involved in protection of sister chromatid cohesion is also lost with age. This can exacerbate the effects of maternal age by rendering residual cohesin at pericentromeres vulnerable to loss in anaphase I. This hints at more extensive alterations to centromere organisation with advanced maternal age. Study design, size, duration This study uses human oocytes deselected from fertility treatment donated for research purposes with informed consent (HFEA RO155). The oocytes were collected fresh at germinal vesicle (GV), metaphase I (MI) or metaphase II (MII) stage, injected with Cas9 labelling system and live imaged or fixed. Participants/materials, setting, methods Centromeres were labelled in human oocytes using a dead (nuclease-deficient) (d)Cas9-EGFP protein and alpha satellite-specific small guide RNAs (sgRNA). Human oocytes were injected with dCas9-EGFP:sgAlphaSat and live-imaged using dual colour confocal microscopy with SPY555-DNA dye to also visualise chromosomes. High resolution imaging results were analysed with in-house automated kinetochore tracking software. Additional oocytes were fixed and processed for immunofluorescence to determine the high resolution localisation of dCas9-EGFP:sgAlphaSat and Sgo2 molecules. Main results and the role of chance We found that centromeres in human oocytes are efficiently labelled when using Cas9 system. During both meiosis I and II the dCas9-EGFP:sgAlphaSat probe co-localised with pericentromeric bridge and subcentromeric pools of Sgo2. We observed that the dCas9-EGFP:sgAlphaSat signal fades with advancing female age. Quantification reveals that in meiosis II the loss is abrupt at around 35 years of age, resembling Sgo2 behaviour. Initial live imaging indicates that already compromised signal in older oocytes is completely lost about 4hrs after germinal vesicle breakdown, suggesting that advancing age renders centromeres more vulnerable as meiosis I progresses. We have successfully tracked the centromeres in high resolution imaging using the automated software, which allows for detailed investigation of human meiosis chromosome dynamics. This method has been previously validated and successfully used for other cell systems. Limitations, reasons for caution Availability of human oocytes for research purposes is low, limiting our sample size. Moreover, most oocytes used for this study were deselected from treatment of patients diagnosed with infertility, potentially affecting their quality. Wider implications of the findings Our results reveal a large-scale change in centromeric DNA structure in human oocytes with increasing age. Live centromere labelling is a first successful attempt to bivalent tracking in human meiosis with potential to provide insight into age-related loss of fertility in women. Trial registration number n/a

Relationship between Financial Risk Exposure and Non-Performing Loans of Commercial Banks in Kenya

Currently, there is a financial crisis affecting commercial banks in Kenya occasioned by high levels of loan loss provision as a result of Non-Performing Loans. The past decade has seen the collapse of major banks like Chase Bank among others. This trend on Non-Performing Loans of the institutions requires urgent measures to reverse failure to which the entire sector is likely to collapse, and customers would lose a significant amount of their deposits. This study sought to investigate the effect of credit risk and liquidity risk on non-performing loans (NPLs) of commercial banks in Kenya and appraise the moderating effect of firm age on the relationship between financial risk exposure on non-performing loans of commercial banks in Kenya. The study was underpinned by liquidity preference theory. The examination adopted a positivist paradigm guided by explanatory research design. The study targeted 40 commercial banks as the unit of analysis while branch managers, operations and risk managers were the units of observation drawn from the banks adding to 120 respondents and census was used. The study collected both primary data using structured questionnaire on the independent variable and secondary data from publications by Central Bank of Kenya (CBK) and respective banks and the same was analyzed through the statistical package for social sciences (SPSS) version 26 in a descriptive and inferential manner. The study established that credit risk (p&lt;0.05) and liquidity risk (p&lt;0.05) were all found to have significant effect on NPLs of commercial banks in Kenya and significantly moderated by their sizes. It was concluded that financial risk exposure has significant effect on NPLs of commercial banks in Kenya. It was recommended that finance manages working in commercial banks in Kenya to balance the investment in short term and long-term assets to maintain operational liquidity levels for better management of liquidity risks. Credit managers working for commercial banks in Kenya need to review the existing credit risk management efforts and mechanisms to minimize exposure to NPLs.

O-033 Molecular insights into the decline in oocyte quality with advanced maternal age: findings from comprehensive single cell -omics analysis of 112 human oocytes

Abstract Study question How does maternal age impact the molecular composition of oocytes during their final meiotic progression? Summary answer Maternal age significantly correlates with proteomic changes during oocyte maturation, particularly in proteostasis and meiosis related proteins, with minimal impact on transcriptome and DNA-methylation patterns. What is known already Oocyte quality declines with maternal age, resulting in diminished developmental competence and higher aneuploidy rates. However, the molecular mechanisms behind this decline in oocyte quality remain elusive. Transcriptomic studies have revealed few differentially expressed genes in advanced maternal age (AMA) oocytes, suggesting that age-related changes in oocyte quality result from a complex interplay of molecular factors, rather than a single cause. However, comprehensive methylation and proteomic data are still lacking. We employed advanced -omics to assess the effect of maternal age on the molecular signature of human oocytes, focusing on DNA-methylation, transcriptome and proteome changes during the final meiotic progression. Study design, size, duration This study included a total of 112 oocytes obtained from young (&amp;lt;35 years, n = 35) and AMA women (&amp;gt;37 years, n = 55), who were recruited in the study from October 2021 to October 2023. Both germinal vesicle (GV, n = 68) and metaphase II (MII, n = 44) oocytes were analysed. Additionally, 19 immature oocytes (GV and metaphase I) from 9 young women were used for validation. Participants/materials, setting, methods Parallel single-cell bisulfite and RNA sequencing was applied to 44 oocytes (26 GV-Young, 6 MII-Young, 8 GV-AMA, 4 MII-AMA) and single-cell proteomics to 68 oocytes (18 GV-Young, 18 MII-Young, 18 GV-AMA, 14 MII-AMA). Additionally, 10 GV and 9 MI oocytes were treated with the proteasome inhibitor MG-312 (0 µM, 10 µM) for 6 hours, followed by rescue in vitro maturation (rIVM) for 36 hours. Chromosomal distribution was assessed by immunocytochemistry. Main results and the role of chance Our analysis revealed no significant changes in DNA methylation patterns in either GV nor MII oocytes associated with AMA. Also, very limited changes were detected in the transcriptome, with transcript levels of only 5 genes in GV oocytes and 7 genes in MII oocytes detected as being significantly changed. In contrast, proteomic analysis, particularly in GV oocytes, revealed significant age-related changes, notably in proteins participating in the proteostasis network (signalosome complex, UCHL1) including chaperones (TRiC-complex, HSP7C, STIP1), and in the cell cycle, including signal transduction factors (1433E, integrins) and cytoskeleton regulators (DYL2, CAPZB, ARHGG) (Rs ≤ |0.5|, p ≤ 0.05). The proteasome complex, which plays a crucial role both in meiosis and the proteostasis network, was found to decline with age; changes were evident in several subunits of the complex (e.g., PRS8, PRS6A, and PRS10; Rs ≤ -0.56, p ≤ 0.05). Compared to controls, treatment of immature oocytes with the proteasome inhibitor MG-132 resulted in either maturation failure or chromosome mislocalization in metaphase plate, further validating the essential role of the proteasome during oocyte maturation. In MII oocytes, 7 proteins showed alterations with age, including the oocyte-specific marker DDX4, which significantly declined in abundance (Rs =-0.6, p ≤ 0.05). Limitations, reasons for caution Unlike GVs that were collected fresh, MII oocytes underwent vitrification and warming before being included in the study due to clinical protocols. These procedures may have unknown effects on the transcriptome and proteome. Wider implications of the findings Our findings suggest that age primarily affects oocyte quality at the post-transcriptional level, potentially through meiosis dysregulation and proteostasis disruption. We also demonstrate the proteasome's vital role in oocyte maturation, suggesting that targeting the proteasome complex may improve oocyte quality in AMA women. Trial registration number Not applicable