Transcript levels of cellular senescence marker genes are increased based on high expression of gasdermin family of genes in breast cancer DOI
Çağlar Berkel

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 24, 2024

Cellular senescence is a cell state characterized by generally permanent cell-cycle arrest, generating broad secretome of inflammatory factors, contributing to pro-inflammatory milieu. Pyroptosis highly regulated death mechanism with characteristics, mediated gasdermin (GSDM) family proteins, which has six members: GSDMA-E and PJVK. In the present study, I found that breast tumors high expression have higher marker genes, namely CDKN1A (encoding p21), CDKN2A p16) TP53 p53). This especially true for GSDMD- or GSDME-expressing tumors, show mRNA levels three genes. GSDM-dependent increases in transcript cellular genes more frequent cancer cells than non-malignant cells, suggesting association between senesence terms strong case tumor. might point that, cancer, pyroptosis be associated; however, whether regulates vice versa, these two processes both reciprocally regulate control each other, even they share an upstream regulatory pathway remains identified. These findings also support previous research demonstrating promoting effect on senesence, SASP (senescence-associated secretory phenotype) factors can induce GSDMD–dependent pyroptotic neighboring present, certain contexts. Further mechanistic studies are required better characterize molecular connections cancer.

Language: Английский

Physiological premature aging of ovarian blood vessels leads to decline in fertility in middle-aged mice DOI Creative Commons

Lu Mu,

Ge Wang,

Xuebing Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Ovarian function declines significantly as females enter middle-age, but the mechanisms underlying this decline remain unclear. Here, we utilize whole-organ imaging to observe a notable decrease in ovarian blood vessel (oBV) density and angiogenesis intensity of middle-aged mice. This leads diminished supply ovaries, resulting inadequate development maturation follicles. Utilizing genetic-modified mouse models, demonstrate that granulosa cell secreted VEGFA governs angiogenesis, physiological oBV is not attributed insufficiency. Instead, through single-cell sequencing, identify aging vascular endothelium primary factor contributing decline. Consequently, administration salidroside, natural compound functional reverse promote enhances improve fertility older females. Our findings highlight enhancing promising strategy boost study identifies key driver loss female mice demonstrates restoring with Salidroside might be approach aged

Language: Английский

Citations

4
Single‐Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging DOI Creative Commons
Chuanchuan Zhou, Qi Guo,

Jiayu Lin

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 11(4)

Published: Nov. 30, 2023

Abstract Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, aging‐related cellular molecular changes human ovaries that occur these years have not been elucidated. Here, single‐cell RNA sequencing (scRNA‐seq) of is performed from different childbearing ages reveals activation pyroptosis pathway increased age, mainly macrophages. The enrichment pyroptotic macrophages leads to switch tissue‐resident macrophage (TRM)‐involve immunoregulatory microenvironment young monocyte‐derived (MDM)‐involved proinflammatory middle‐aged ovaries. This remolded ovarian immuno‐microenvironment further promotes stromal cell senescence accelerated decline. hypothesis validated series animal experiments using GSDMD‐KO mice. In conclusion, work expands current understanding aging process by illustrating macrophage‐involved immune mechanism, has important implications for development novel strategies delay promote health.

Language: Английский

Citations

28
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

17
Harnessing omics data for drug discovery and development in ovarian aging DOI
Fengyu Zhang, Zhu Ming, 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

1
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

1
Reproductive Ageing: Inflammation, immune cells, and cellular senescence in the aging ovary DOI Creative Commons

José V. V. Isola,

Jéssica D. Hense,

César A P Osório

et al.

Reproduction, Journal Year: 2024, Volume and Issue: 168(2)

Published: May 13, 2024

In brief Recent reports suggest a relationship between ovarian inflammation and functional declines, although it remains unresolved if is the cause or consequence of aging. this review, we compile available literature in area point to several current knowledge gaps that should be addressed through future studies. Abstract Ovarian aging results reduced fertility, disrupted endocrine signaling, an increased burden chronic diseases. The factors contributing natural decline follicles throughout reproductive life are not fully understood. Nevertheless, local may play important role driving Inflammation progressively rises aged ovaries during window, potentially affecting fertility. addition inflammatory markers, recent studies show accumulation specific immune cell populations ovaries, particularly lymphocytes. Other hallmarks ovary include formation multinucleated giant cells, collagen deposition, markers cellular senescence. Collectively, these changes significantly impact quantity quality oocytes. This review explores on alterations associated with inflammation, fibrosis, senescence, cells ovary.

Language: Английский

Citations

8
The role of cellular senescence in ovarian aging DOI Creative Commons
Jéssica D. Hense, José V.V. Isola, Driele N. Garcia

et al.

npj Aging, Journal Year: 2024, Volume and Issue: 10(1)

Published: July 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.

Language: Английский

Citations

8
Primary oocytes with cellular senescence features are involved in ovarian aging in mice DOI Creative Commons
Hao Yan, Edgar Andres Diaz Miranda,

Shiying Jin

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 13, 2024

Abstract In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal function egg production via folliculogenesis. The loss of causes aging. Cellular senescence, characterized by cell cycle arrest senescence-associated secretory phenotype (SASP), is associated with tissue present study, we report that some primary oocytes in become senescent adult mouse ovaries. share senescence markers somatic cells. were observed young ovaries, remained at approximately 15% total during aging from 6 to 12 months, accumulated aged Administration a senolytic drug ABT263 3-month-old mice reduced percentage transcription SASP factors ovary, addition, led increased numbers higher rate oocyte maturation. Our study provides experimental evidence oocytes, germline type arrested meiosis, ovaries clearance follicle mitigated phenotypes.

Language: Английский

Citations

4
Investigations on the effects of in vitro exposure of mouse ovaries to withaferin A, a new candidate for chemotherapy DOI
Gaby Judith Quispe Palomino,

Rensson Homero Céliz Ygnacio,

Laritza Ferreira de Lima

et al.

Reproductive Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 108844 - 108844

Published: Jan. 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