The influence of the gut microbiome on ovarian aging

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 3, 2024

Ovarian aging occurs prior to the of other organ systems and acts as pacemaker process multiple organs. As life expectancy has increased, preventing ovarian become an essential goal for promoting extended reproductive function improving bone genitourinary conditions related in women. An improved understanding may ultimately provide tools prediction mitigation this process. Recent studies have suggested a connection between gut microbiota, alterations composition functional profile microbiota profound consequences on function. The interaction ovaries is bidirectional. In review, we examine current knowledge ovary-gut crosstalk further discuss potential role anti-aging interventions. Microbiota-based manipulation appealing approach that offer new therapeutic strategies delay or reverse aging.

Language: Английский

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Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: April 17, 2024

Mitochondria plays an essential role in regulating cellular metabolic homeostasis, proliferation/differentiation, and cell death. Mitochondrial dysfunction is implicated many age-related pathologies. Evidence supports that the of mitochondria decline mitochondrial DNA copy number negatively affect ovarian aging. However, mechanism aging still unclear. Treatment methods, including antioxidant applications, transplantation, emerging biomaterials, advanced technologies, are being used to improve function restore oocyte quality. This article reviews key evidence research updates on damage pathogenesis aging, emphasizing may accelerate lead senescence as well exploring potential methods for using mechanisms slow down

Language: Английский

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Crocetin Prolongs Recovery Period of DSS-Induced Colitis via Altering Intestinal Microbiome and Increasing Intestinal Permeability

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3832 - 3832

Published: March 30, 2022

Crocetin is one of the major active constituents saffron (Crocus sativus L.) which has a reputation for facilitating blood circulation and dispersing stasis in traditional Chinese medicine. However, there little evidence showing relationship between crocetin intake risk gastrointestinal diseases such as colitis. In order to investigate effect on regulation intestinal barrier function microbiota composition, mice were treated with after 3% dextran sulfate sodium (DSS) administration week. We found that at 10 mg/kg aggravated colitis mice, increased weight loss more serious histological abnormalities compared DSS group. The 16s rDNA sequencing analysis feces samples showed had lower species diversity richness than those DSS. At genus level, higher abundance Akkermansia Mediterraneibacter, Muribaculaceae, Dubosiella, Paramuribaculum, Parasutterella, Allobaculum, Duncaniella, Candidatus Stoquefichus, Coriobacteriaceae UCG-002 observed Untargeted metabolomic analyses revealed reduced levels primary secondary bile acids 12-ketodeoxycholic acid, 7-ketodeoxycholic 3-sulfodeoxycholic 6-ethylchenodeoxycholic chenodeoxycholate, glycochenodeoxycholate-7-sulfate, glycocholate, sulfolithocholic acid colon. conclusion, disturbed homeostasis prolonged recovery by promoting inflammation altering gut composition its metabolic products mice. Our findings suggest patients inflammatory bowel disease should use caution.

Language: Английский

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Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma

Molecular Carcinogenesis, Journal Year: 2024, Volume and Issue: 63(4), P. 577 - 588

Published: Jan. 10, 2024

Abstract Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. cells were treated with NMN (125, 250, and 500 μM), then adenine dinucleotide (NAD + ) NADH levels measured to calculate NAD /NADH ratio. Cell proliferation, apoptosis, autophagy ferroptosis determined. AMPK was knocked down confirm involvement AMPK/mTOR signaling. Furthermore, tumor‐inhibitory effect xenograft models. Exposure dose‐dependently increased level ratio cells. After treatment, cell proliferation inhibited, whereas apoptosis enhanced both lines. Additionally, autophagy/ferroptosis activated pathway knockdown partially rescued effects vitro. treatment restrained tumor growth nude mice, autophagy/ferroptosis, promoted necrosis tissues. The results indicate that inhibits progression by inducing via may serve as promising agent for treatment.

Language: Английский

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Mitochondria as therapeutic targets in assisted reproduction

Human Reproduction, Journal Year: 2024, Volume and Issue: 39(10), P. 2147 - 2159

Published: July 25, 2024

Abstract Mitochondria are essential organelles with specialized functions, which play crucial roles in energy production, calcium homeostasis, and programmed cell death. In oocytes, mitochondrial populations inherited maternally vital for developmental competence. Dysfunction quality control mechanisms can lead to reproductive failure. Due their central role oocyte embryo development, mitochondria have been investigated as potential diagnostic therapeutic targets assisted reproduction. Pharmacological agents that target function show promise improving reproduction outcomes include antioxidant coenzyme Q10 mitoquinone, mammalian of rapamycin signaling pathway inhibitor rapamycin, nicotinamide mononucleotide. Mitochondrial replacement therapies (MRTs) offer solutions infertility disorders. Autologous germline transfer initially showed but failed demonstrate significant benefits clinical trials. Maternal spindle (MST) pronuclear hold preventing disease transmission quality. Clinical trials MST shown promising outcomes, larger studies needed confirm safety efficacy. However, ethical legislative challenges complicate the widespread implementation MRTs.

Language: Английский

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Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation

Autophagy, Journal Year: 2022, Volume and Issue: 19(1), P. 163 - 179

Published: April 11, 2022

Macroautophagy/autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, anti-ovarian aging. However, it remains unknown whether autophagy in granulosa cells affects oocyte maturation. Here, we show clear tendency reduced level human from women advanced maternal age, implying potential negative correlation between levels quality. We therefore established co-culture system either pharmacological inhibition or genetic ablation negatively affect quality fertilization ability. Moreover, our metabolomics analysis indicates adverse impact impairment on mediated by downregulated citrate levels, while exogenous supplementation can significantly restore Mechanistically, found ACLY (ATP lyase), which crucial enzyme catalyzing cleavage citrate, was preferentially associated with K63-linked ubiquitin chains recognized receptor protein SQSTM1/p62 for selective autophagic degradation. In aging, accompanied decreased follicular fluid, metabolism also elevated porcine fluid promote Collectively, data reveal beneficial certain degree selectively targeting during

Language: Английский

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Ovarian aging: mechanisms and intervention strategies

Medical Review, Journal Year: 2022, Volume and Issue: 2(6), P. 590 - 610

Published: Nov. 21, 2022

Abstract Ovarian reserve is essential for fertility and influences healthy aging in women. Advanced maternal age correlates with the progressive loss of both quantity quality oocytes. The molecular mechanisms various contributing factors underlying ovarian have been uncovered. In this review, we highlight some critical that impact oocyte during aging. Germ cell follicle at birth determines reproductive lifespan timing menopause female mammals. Accelerated diminishing leads to premature or insufficiency. Poor increasing could result from chromosomal cohesion deterioration misaligned chromosomes, telomere shortening, DNA damage associated genetic mutations, oxidative stress, mitochondrial dysfunction epigenetic alteration. We also discuss intervention strategies delay Both efficacy senotherapies by antioxidants against therapy are discussed. Functional oocytes ovarioids be rejuvenated pluripotent stem cells somatic cells. propose directions future interventions. As couples increasingly begin delaying parenthood life worldwide, understanding potential benefit women making earlier choices about their health.

Language: Английский

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CD38 regulates ovarian function and fecundity via NAD+ metabolism

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107949 - 107949

Published: Sept. 16, 2023

Language: Английский

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Impact of NAD+ metabolism on ovarian aging

Immunity & Ageing, Journal Year: 2023, Volume and Issue: 20(1)

Published: Dec. 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

Language: Английский

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Investigation of He’s Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 27, 2023

Background Primary ovarian insufficiency (POI) is a common gynecological disease with serious ramifications including low pregnancy rate and estrogen symptoms. Traditional Chinese medicine regarded as an effective treatment for POI. However, the therapeutic mechanism of it unclear. Methods In this study, mouse model primary was established by intraperitoneal injection cyclophosphamide (CTX) He’s Yang Chao Recipe (HSYC) concentrate used intragastric administration. Serum hormone levels (Anti-Müllerian Hormone, Estradiol, Progesterone, Luteinizing Hormone Follicle Stimulating Hormone) Oxidative Stress (OS) related products, superoxide dismutase (SOD), GSH-Px, malondialdehyde (MDA) were measured enzyme-linked immunosorbent assay. Pathological changes in tissue evaluated hematoxylin eosin staining, flow cytometry to determine reactive oxygen species content mitochondrial membrane potential granulosa cells. Mitochondrial distribution morphology investigated using immunofluorescence staining. The level mitophagy LC3 staining autophagosome counts electron microscopy. Western blotting qPCR detect expression proteins genes NLRP3 inflammasome. Results After HSYC treatment, damage milder than CTX group. Compared group; SOD, total antioxidant capacity significantly increased, while MDA ROS decreased groups. Furthermore, improved after compared fluorescent intensity decreased. Similarly, markers PINK1, Parkin, LC3, Beclin1 decreased, p62 mRNA protein inflammasome, NLRP3, caspase-1, GSDMD, IL-18, IL-1β Conclusion This first study molecular mechanisms underlying against cell injury protects ovaries from CTX-induced oxidative stress. enhanced function mice inhibiting PINK1-Parkin inflammasome activation.

Language: Английский

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