Hallmarks of female reproductive aging in physiologic aging mice DOI
Julia L. Balough, Shweta S. Dipali, Karen M Velez

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(12), P. 1711 - 1730

Published: Dec. 13, 2024

Language: Английский

Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage DOI Creative Commons

Yican Guo,

Liru Xue,

Weicheng Tang

et al.

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(5), P. 614 - 647

Published: June 28, 2024

Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance hormone levels, reduced or lost fertility, an increased risk early menopause. Previous studies have often focused on direct chemotherapeutic drugs follicles, such as DNA damage-mediated apoptotic death primordial follicle burnout. Emerging evidence has revealed imbalance microenvironment during chemotherapy. The provides nutritional support transportation signals stimulate growth development ovulation, corpus luteum formation. close interaction between follicles determine function. Therefore, designing novel precise strategies manipulate may be a new strategy protect function

Language: Английский

Citations

14

Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases DOI
Zeming Wu, Jing Qu, Guang‐Hui Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 979 - 1000

Published: Oct. 3, 2024

Language: Английский

Citations

7

CALB1 and RPL23 Are Essential for Maintaining Oocyte Quality and Function During Aging DOI Creative Commons

Yingxue Han,

Zihuan Du,

Hao Wu

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

ABSTRACT With advancing age, significant changes occur in the female reproductive system, most notable of which is decline oocyte quality, a key factor affecting fertility. However, mechanisms underlying aging remain poorly understood. In this study, we obtained oocytes from aged and young mice performed single‐cell transcriptome sequencing, comparing our findings with existing proteomic analyses. Our analysis revealed that one primary characteristics disruption calcium ion homeostasis. Specifically, identified two genes involved process, Calb1 Rpl23 . Experimental validation demonstrated knockdown CALB1 led to reduced levels endoplasmic reticulum mitochondria, resulting mitochondrial dysfunction meiotic defects. Further experiments suggested RPL23 may function as downstream gene CALB1, its caused dysfunction, excessive accumulation reactive oxygen species (ROS), spindle assembly Notably, overexpression these partially rescued maternal age‐related defective phenotypes, underscoring their crucial roles aging. This study provides comprehensive understanding specific mouse at resolution, supported by experimental validation, offers new directions potential targets for future research into health issues.

Language: Английский

Citations

0

Exploration of the mechanism and therapy of ovarian aging by targeting cellular senescence DOI Creative Commons
Weicheng Tang, Kaichen Wang, Yourong Feng

et al.

Life Medicine, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 23, 2025

The ovary is a crucial gonadal organ that supports female reproductive and endocrine functions. Ovarian aging can result in decreased fertility dysfunction across multiple organs. Research has demonstrated cellular senescence various cell types within the trigger decline ovarian function through distinct stress responses, resulting aging. This review explores how may contribute to failure. Additionally, we discuss factors cause senescence, including accumulation of advanced glycation end products, oxidative stress, mitochondrial dysfunction, DNA damage, telomere shortening, exposure chemotherapy. Furthermore, six types, oocytes, granulosa cells, theca immune surface epithelium, endothelial inside explore their contribution accelerated Lastly, describe potential senotherapeutics for treatment offer novel strategies longevity.

Language: Английский

Citations

0

Improving Spatial Transcriptomics with Membrane‐Based Boundary Definition and Enhanced Single‐Cell Resolution DOI Open Access
Song Li, Liqun Wang,

Zitian He

et al.

Small Methods, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Abstract Accurately defining cell boundaries for spatial transcriptomics is technically challenging. The current major approaches are nuclear staining or mathematical inference, which either exclude the cytoplasm determine a hypothetical boundary. Here, new method introduced boundaries: labeling membranes using genetically coded fluorescent proteins, allows precise indexing of sequencing spots and transcripts within cells on sections. Use this membrane‐based greatly increases number genes captured in compared to nucleus‐based methods; numbers increased by 67% 119% mouse axolotl livers, respectively. obtained expression profiles more consistent with single‐cell RNA‐seq data, demonstrating rational clustering apparent type‐specific markers. Furthermore, improved resolution achieved better identify rare types elaborate domains brain intestine. In addition regular cells, accurate recognition multinucleated lacking nuclei liver achieved, its ability analyze complex tissues organs, not achievable previous methods. This study provides powerful tool improving that has broad potential applications biological medical sciences.

Language: Английский

Citations

0

Harnessing omics data for drug discovery and development in ovarian aging DOI
Fengyu Zhang, Ming Zhu, Yi Chen

et al.

Human Reproduction Update, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

0

Hallmarks of ovarian aging DOI

Chuqing Wu,

Dan Chen, Michael B. Stout

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0

Reduced DNMT1 expression associated with TP53 promoter hypomethylation mediate enhanced granulosa cell senescence during ovarian aging DOI Creative Commons
Hui Guo,

Shuhong Pan,

Jian Zhao

et al.

Gynecological Endocrinology, Journal Year: 2025, Volume and Issue: 41(1)

Published: Feb. 26, 2025

Background The effects of granulose cell (GC) senescence on premature ovarian insufficiency/premature failure have been extensively examined, the association between GC and aging remains to be clarified.

Language: Английский

Citations

0

Multi-omics analysis of the dynamic role of STAR+ cells in regulating platinum-based chemotherapy responses and tumor microenvironment in serous ovarian carcinoma DOI Creative Commons

Hongwei Lan,

Wei‐Hua Yan, Xiao Hu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Background Serous ovarian carcinoma (SOC) is the most lethal subtype of cancer, with chemoresistance to platinum-based chemotherapy remaining a major challenge in improving clinical outcomes. The role tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), modulating responses not yet fully understood. Methods To explore relationship between CAF subtypes and sensitivity, we employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry (IHC), immunofluorescence (IF). This multi-omics approach enabled identification, characterization, functional analysis both chemotherapy-sensitive chemotherapy-resistant SOC patients. Results We identified steroidogenic acute regulatory protein-positive (STAR+) cells as novel enriched STAR + exhibited unique transcriptional profiles were functionally pathways related P450 drug metabolism, lipid amino acid enhanced pathway activity observed groups. Spatial transcriptomics IF revealed that closely localized cells, suggesting potential cell-cell interactions. Further communication indicated may suppress WNT signaling contributing improved responses. Importantly, expression levels, validated by IHC, positively correlated sensitivity patient prognosis. Platinum-based was shown increase proportion underscoring their dynamic response treatment. Conclusion Our study identifies enhances SOC. By key metabolic potentially suppressing signaling, could contribute treatment These findings position promising biomarker for predicting efficacy SOC, which warrants further investigation.

Language: Английский

Citations

0

Comparative analysis of human and mouse ovaries across age DOI Creative Commons
Eliza A. Gaylord, Mariko H. Foecke, Ryan M. Samuel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Mouse is a tractable model for human ovarian biology, however its utility limited by incomplete understanding of how transcription and signaling differ interspecifically with age. We compared ovaries between species using 3D-imaging, single-cell transcriptomics, functional studies. In mice, we mapped declining follicle numbers oocyte competence during aging; in ovaries, identified cortical pockets density changes. Oocytes had species-specific gene expression patterns growth that converged toward maturity. Age-related transcriptional changes were greater oocytes than granulosa cells across species, although mature change more humans. sympathetic nerves glia; nerve increased aged and, when ablated perturbed folliculogenesis. This comparative atlas defines shared hallmarks biology.

Language: Английский

Citations

0