Causal role of immune cells in ovarian dysfunction :a mendelian randomization study DOI Creative Commons

Ruoxin Weng,

Shuyi Ling,

Yuqing Dai

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 29, 2024

Abstract Background At present, the etiology and mechanism of ovarian dysfunction are still unclear.Recent studies have indicated a potential correlation between immunity dysfunction. However, causal relationship immune cells remains uncertain. For this aiticle,we aimed to figure out whether changes cell composition contribute in article. Methods Comprehensive two-sample Mendelian randomization analysis was performed determine role compostitions study. The data derived from latest GWAS blood shape summary statistical Catalog, were obtained IEU Open GWAS. A total 942 cases 18,228 controls included. variety analytical methods, including inverse variance weighting, weighted median, MR-Egggera etc, utilized explore link Cochran's Q statistics used evaluate heterogeneity instrumental variables. MR-Egger MR pleiotropic residuals outlier tests detect horizontal pleiotropy. funnel plots scatter visually assess robustness. Results Our findings suggest that presence 36 phenotypes had significant effect on Among them, 18 immunophenotypes positively associated with dysfunction, 7 B panel, 9 T 1 monocyte panel NK panel; 28 negatively 11 14 panel. Conclusion study has demonstrated close connection by genetic background analysis. Further research is necessary these as early predictors well possibility new preventive strategies therapeutic targets.

Язык: Английский

NADase CD38 is a key determinant of ovarian aging DOI Creative Commons
Qingling Yang, Wenhui Chen, Luping Cong

и другие.

Nature Aging, Год журнала: 2023, Номер 4(1), С. 110 - 128

Опубликована: Дек. 21, 2023

Abstract The ovary ages earlier than most other tissues, yet the underlying mechanisms remain elusive. Here a comprehensive analysis of transcriptomic landscapes in different organs young and middle-aged mice revealed that ovaries showed expression age-associated genes, identifying increased NADase CD38 decreased NAD + levels mice. Bulk single-cell RNA sequencing deletion mitigated ovarian aging, preserving fertility follicle reserve aged by countering age-related gene changes intercellular communication alterations. Mechanistically, onset inflammation induced higher ovary, thereby accelerating aging. Consistently, pharmacological inhibition enhanced Our findings aging relative to organs, providing potential therapeutic target for ameliorating female infertility.

Язык: Английский

Процитировано

33
The therapeutic perspective of NAD+ precursors in age-related diseases DOI Creative Commons
Tooba Iqbal, Takashi Nakagawa

Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 702, С. 149590 - 149590

Опубликована: Фев. 2, 2024

Nicotinamide adenine dinucleotide (NAD

Процитировано

16
Harnessing omics data for drug discovery and development in ovarian aging DOI
Fengyu Zhang, Zhu Ming, Yi Chen

и другие.

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

Процитировано

1
Impact of NAD+ metabolism on ovarian aging DOI Creative Commons

Jinghui Liang,

Feiling Huang, Zhaoqi Song

и другие.

Immunity & Ageing, Год журнала: 2023, Номер 20(1)

Опубликована: Дек. 2, 2023

Abstract Nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular redox reactions, is closely associated with age-related functional degeneration and metabolic diseases. NAD exerts direct indirect influences on many functions, including pathways, DNA repair, chromatin remodeling, senescence, immune cell functionality. These processes functions are essential for maintaining tissue homeostasis, as well healthy aging. Causality has been elucidated between decline levels multiple diseases, which confirmed by various strategies aimed at increasing the preclinical setting. Ovarian aging recognized natural process characterized follicle number function, resulting decreased estrogen production menopause. In this regard, it necessary to address factors involved complicated procedure, could improve fertility women of advanced maternal age. Concerning decrease NAD+ ovarian progresses, promising exciting results presented using precursors promote biosynthesis, substantially oocyte quality alleviate Hence, acquire further insights into metabolism biology, review aims probe affecting aging, characteristics precursors, current research status supplementation Specifically, gaining comprehensive understanding these aspects, we optimistic about prominent progress that will be made both therapy related

Язык: Английский

Процитировано

19
The role of cellular senescence in ovarian aging DOI Creative Commons
Jéssica D. Hense, José V.V. Isola, Driele N. Garcia

и другие.

npj Aging, Год журнала: 2024, Номер 10(1)

Опубликована: Июль 20, 2024

Abstract This review explores the relationship between ovarian aging and senescent cell accumulation, as well efficacy of senolytics to improve reproductive longevity. Reproductive longevity is determined by age-associated decline in reserve, resulting reduced fertility eventually menopause. Cellular senescence a state permanent cycle arrest resistance apoptosis. Senescent cells accumulate several tissues with advancing age, thereby promoting chronic inflammation age-related diseases. Ovaries also appear which might contribute system whole organism through SASP production. Importantly, senolytic drugs can eliminate may present potential intervention mitigate aging. Herein, we current literature related for extending window mice.

Язык: Английский

Процитировано

8
Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan DOI Creative Commons
Ewa Bomba-Warczak, Karen M Velez, Luhan T. Zhou

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Янв. 25, 2024

The mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries gametes across lifespan. Ovaries exhibit localized structural cell-type-specific enrichment both follicular extrafollicular environments. Moreover, oocytes harbor panel long-lived including cytoskeletal, mitochondrial, oocyte-derived proteins. exceptional persistence these molecules suggest critical role lifelong maintenance age-dependent tissues.

Язык: Английский

Процитировано

6
Astragalin from Thesium chinense: A Novel Anti-Aging and Antioxidant Agent Targeting IGFR/CD38/Sirtuins DOI Creative Commons
Ruifeng Wang,

Anping Ding,

Jiaye Wang

и другие.

Antioxidants, Год журнала: 2024, Номер 13(7), С. 859 - 859

Опубликована: Июль 18, 2024

Astragalin (AG), a typical flavonoid found in Thesium chinense Turcz (T. chinense), is abundant various edible plants and possesses high nutritional value, as well antioxidant antibacterial effects. In this study, we initially predicted the mechanism of action AG with two anti-aging antioxidant-related protein targets (CD38 IGFR) by molecular docking dynamics simulation techniques. Subsequently, examined effects Caenorhabditis elegans (C. elegans), zebrafish, verified related mechanisms. C. elegans, synergistically extended lifespan up-regulating expression daf-16 through inhibiting daf-2/IGFR also activating AMPK MAPK pathways to up-regulate sir-2.1, sir-2.4, skn-1. oxidatively damaged zebrafish embryos, demonstrated synergistic effect augmenting resistance embryos oxidative stress levels SIRT1 SIRT6 within system via suppression CD38 enzymatic activity then IGFR SIRT6. These findings highlight properties indicate its potential application supplementary ingredient aquaculture for enhancing fish health growth.

Язык: Английский

Процитировано

5
Exploring nicotinamide adenine dinucleotide precursors across biosynthesis pathways: Unraveling their role in the ovary DOI
Caifang Ren,

Zhang Shuang,

Yanyan Chen

и другие.

The FASEB Journal, Год журнала: 2024, Номер 38(14)

Опубликована: Июль 22, 2024

Abstract Natural Nicotinamide Adenine Dinucleotide (NAD + ) precursors have attracted much attention due to their positive effects in promoting ovarian health. However, target tissue, synthesis efficiency, advantages, and disadvantages are still unclear. This review summarizes the distribution of NAD at cellular subcellular levels, discusses its biosynthetic pathways latest findings ovary, include: (1) plays distinct roles both intracellularly extracellularly, adapting response requirements. (2) Different differs tissues, synthetic biological utilization, adverse effects. Importantly: tryptophan is primarily utilized liver kidneys, posing metabolic risks excess; nicotinamide (NAM) indispensable for maintaining levels; nicotinic acid (NA) constructs a crucial bridge between intestinal microbiota host with diverse functions; riboside (NR) mononucleotide (NMN) increase systemically can be influenced by delivery route, tissue specificity, transport efficiency. (3) The intricately intertwined. They provide multiple sources techniques synthesis, thereby reducing dependence on single molecule maintain levels. an excess specific precursor potentially influencing other pathways. In addition, Protein expression analysis suggest that tissues may preferentially utilize NAM NMN. These summarize potential enhancing Future research should delve into molecular mechanisms intervention strategies different precursors, aiming achieve personalized prevention or treatment diseases, reveal clinical application value.

Язык: Английский

Процитировано

5
Exceptional longevity of mammalian ovarian and oocyte macromolecules throughout the reproductive lifespan DOI Creative Commons
Ewa Bomba-Warczak, Karen M Velez, Luhan T. Zhou

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Окт. 31, 2024

The mechanisms contributing to age-related deterioration of the female reproductive system are complex, however aberrant protein homeostasis is a major contributor. We elucidated exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries gametes across lifespan. Ovaries exhibit localized structural cell-type-specific enrichment both follicular extrafollicular environments. Moreover, oocytes harbor panel long-lived including cytoskeletal, mitochondrial, oocyte-derived proteins. exceptional persistence these molecules suggest critical role lifelong maintenance age-dependent tissues.

Язык: Английский

Процитировано

5
Fertility protection during chemotherapy treatment by boosting the NAD(P)+ metabolome DOI Creative Commons

Wing-Hong Jonathan Ho,

Maria B. Marinova,

Dave R. Listijono

и другие.

EMBO Molecular Medicine, Год журнала: 2024, Номер 16(10), С. 2583 - 2618

Опубликована: Авг. 21, 2024

Язык: Английский

Процитировано

4