Hallmarks of ovarian aging

Trends in Endocrinology and Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

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The importance of family-based sampling for biobanks

Nature, Год журнала: 2024, Номер 634(8035), С. 795 - 803

Опубликована: Окт. 23, 2024

Язык: Английский

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Assessing the contribution of rare protein-coding germline variants to prostate cancer risk and severity in 37,184 cases

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 19, 2025

Abstract To assess the contribution of rare coding germline genetic variants to prostate cancer risk and severity, we perform here a meta-analysis 37,184 cases 331,329 male controls from five cohorts with whole exome or genome sequencing data, one cohort imputed array data. At gene level, our case-control collapsing analysis confirms associations between damaging in four genes increased risk: SAMHD1 , BRCA2 ATM at study-wide significance level ( P < 1×10 −8 ), CHEK2 suggestive threshold 2.6×10 −6 ). Our case-only analysis, reveals that AOX1 are associated more aggressive disease (OR = 2.60 [1.75–3.83], 1.35×10 as well confirming role determining severity. single-variant study missense variant TERT is substantially reduced 0.13 [0.07–0.25], 4.67×10 −10 non-synonymous further three ANO7 SPDL1 AR ) HOXB13 BIK Altogether, this work provides deeper insights into architecture biological basis potential implications for clinical prediction therapeutic strategies.

Язык: Английский

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Harnessing omics data for drug discovery and development in ovarian aging

Human Reproduction Update, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Ovarian aging occurs earlier than the of many other organs and has a lasting impact on women's overall health well-being. However, effective interventions to slow ovarian remain limited, primarily due an incomplete understanding underlying molecular mechanisms drug targets. Recent advances in omics data resources, combined with innovative computational tools, are offering deeper insight into complexities aging, paving way for new opportunities discovery development. This review aims synthesize expanding multi-omics data, spanning genome, transcriptome, proteome, metabolome, microbiome, related from both tissue-level single-cell perspectives. We will specially explore how analysis these emerging datasets can be leveraged identify novel targets guide therapeutic strategies slowing reversing aging. conducted comprehensive literature search PubMed database using range relevant keywords: age at natural menopause, premature insufficiency (POI), diminished reserve (DOR), genomics, transcriptomics, epigenomics, DNA methylation, RNA modification, histone proteomics, metabolomics, lipidomics, single-cell, genome-wide association studies (GWAS), whole-exome sequencing, phenome-wide (PheWAS), Mendelian randomization (MR), epigenetic target, machine learning, artificial intelligence (AI), deep multi-omics. The was restricted English-language articles published up September 2024. Multi-omics have uncovered key driving including damage repair deficiencies, inflammatory immune responses, mitochondrial dysfunction, cell death. By integrating researchers critical regulatory factors across various biological levels, leading potential Notable examples include genetic such as BRCA2 TERT, like Tet FTO, metabolic sirtuins CD38+, protein BIN2 PDGF-BB, transcription FOXP1. advent cutting-edge technologies, especially technologies spatial provided valuable insights guiding treatment decisions become powerful tool aimed mitigating or As technology advances, integration AI models holds more accurately predict candidate convergence offers promising avenues personalized medicine precision therapies, tailored Not applicable.

Язык: Английский

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A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 28, 2025

Lung and gastrointestinal diseases often occur together, leading to more adverse health outcomes than when a disease of one these systems occurs alone. However, the potential genetic mechanisms underlying lung-gastrointestinal comorbidities remain unclear. Here, we leverage lung trait data from individuals European, East Asian African ancestries, perform large-scale cross analysis, followed by functional annotation Mendelian randomization analysis explore involved in development comorbidities. Notably, find significant correlations between 27 pairs among European population. The highest correlation is chronic bronchitis peptic ulcer disease. At variant level, identify 42 candidate pleiotropic variants (3 them previously uncharacterized) 14 integrating cross-trait meta-analysis, fine-mapping colocalization analyses. We also 66 genes, most which were enriched immune or inflammatory response-related activities. Causal inference approaches result 4 associations. Introducing gut microbiota as variable establishes relationship genus Parasutterella, gastro-oesophageal reflux asthma. In summary, our findings highlight diseases, providing insights into

Язык: Английский

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Ovarian vascular aging: a hidden driver of mid-age female fertility decline

npj Aging, Год журнала: 2025, Номер 11(1)

Опубликована: Март 30, 2025

Although ovarian reserve remains sufficient, function declines in mid-age, leading to reduced fertility around age 35, with the causes remaining unclear. Recent studies highlight vascular aging as a key factor this decline, age-related reductions remodeling disrupting oocyte development. Salidroside, natural compound that reverses and promotes angiogenesis, presents promising strategy rejuvenate health enhance fertility, offering potential for preserving reproductive aged women.

Язык: Английский

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Common variation in meiosis genes shapes human recombination phenotypes and aneuploidy risk

Опубликована: Апрель 4, 2025

Abstract The leading cause of human pregnancy loss is aneuploidy, often tracing to errors in chromosome segregation during female meiosis. While abnormal crossover recombination known confer risk for limited data have hindered understanding the potential shared genetic basis these key molecular phenotypes. To address this gap, we performed retrospective analysis preimplantation testing from 139,416 vitro fertilized embryos 22,850 sets biological parents. By transmission haplotypes, identified 3,656,198 crossovers, as well 92,485 aneuploid chromosomes. Counts crossovers were lower versus euploid embryos, consistent with their role pairing and segregation. Our analyses further revealed that a common haplotype spanning meiotic cohesin SMC1B significantly associated both count maternal evidence supporting non-coding cis -regulatory mechanism. Transcriptome- phenome-wide association tests also implicated variation synaptonemal complex component C14orf39 crossover-regulating ubiquitin ligases CCNB1IP1 RNF212 aneuploidy risk. More broadly, possess partially overlaps reproductive aging traits. findings highlight dual generating diversity, while ensuring fidelity.

Язык: Английский

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Molecular characteristics of early- and late-onset ovarian cancer: insights from multidimensional evidence

Journal of Ovarian Research, Год журнала: 2025, Номер 18(1)

Опубликована: Апрель 23, 2025

Ovarian cancer (OC) is among the most lethal gynecologic malignancies, characterized by poor prognosis. While aging a well-established risk factor, underlying mechanisms distinguishing early- and late-onset ovarian remain poorly understood. This study analyzed global burden age-related trends of using GBD database. A cut-off age 55 years was used to differentiate between early late onset cancer, Mendelian randomization method also investigate causal relationship cancer. Machine learning applied identify tumor-specific age-associated genes, followed bioinformatics analyses single-cell sequencing explore roles these genes immune profile alterations in Additionally, models were constructed, drug sensitivity performed evaluate their potential as diagnostic markers or therapeutic targets. incidence mortality exhibit trends, with telomere length positively associated increased (OR = 1.27, 95% CI: 1.01-1.60, P 3.90 × 10⁻2). Older patients OC have worse PRKCD UCP2 significantly upregulated facilitates epithelial-mesenchymal transition (EMT), contributing progression, while modulates ROS dynamics, influencing chemoresistance. Immune microenvironment analysis revealed differences high- low-expression groups, particularly T cells, macrophages, other cells. Both are sensitive varity drugs, including dasatinib, fluvastatin, highlighting Aging significant factor for closely linked its progression. These show promise novel biomarkers targets

Язык: Английский

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Genetic determinants of proteomic aging

npj Aging, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 26, 2025

Abstract Changes in the proteome and its dysregulation have long been known to be a hallmark of aging. We derived proteomic aging trait using data on 1459 plasma proteins from 44,435 UK Biobank individuals measured an antibody-based assay. This metric is strongly associated with four age-related disease outcomes, even after adjusting for chronological age. Survival analysis showed that one-year older age, relative increases all-cause mortality hazard by 13 percent. performed genome-wide association age acceleration (proteomic minus age) identify biological determinants. Proteomic modest genetic correlations epigenetic clocks ( R g = 0.17 0.19) telomere length −0.2). Once we removed associations were explained single pQTL, left three signals mapping BRCA1 , POLR2A TET2 apparent widespread effects Genetic variation at these loci has shown affect other omics-related measures. Mendelian randomisation analyses causal higher BMI type 2 diabetes faster acceleration. supports idea obesity features metabolic syndrome adverse effect processes human

Язык: Английский

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Perspectives on biomarkers of reproductive aging for fertility and beyond

Nature Aging, Год журнала: 2024, Номер 4(12), С. 1697 - 1710

Опубликована: Дек. 13, 2024

Язык: Английский

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