Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 13144 - 13144

Опубликована: Дек. 6, 2024

The efficacy of assisted reproductive technologies (ARTs) in older women remains constrained, largely due to an incomplete understanding the underlying pathophysiology. This review aims consolidate current knowledge on age-associated mitochondrial alterations and their implications for ovarian aging, with emphasis causes DNA (mtDNA) mutations, repair mechanisms, future therapeutic directions. Relevant articles published up 30 September 2024 were identified through a systematic search electronic databases. free radical theory proposes that reactive oxygen species (ROS) inflict damage mtDNA impair function essential ATP generation oocytes. Oocytes face prolonged pressure persisting five decades. MtDNA exhibits limited capacity double-strand break repair, heavily depending poly ADP-ribose polymerase 1 (PARP1)-mediated single-strand breaks. process depletes nicotinamide adenine dinucleotide (NAD⁺) ATP, creating detrimental cycle where continued further compromises oocyte functionality. Interventions interrupt this destructive may offer preventive benefits. In conclusion, cumulative burden mutations demands can lead depletion elevate risk aneuploidy, ultimately contributing ART failure women.

Язык: Английский

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

Hallmarks of ovarian aging

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

Опубликована: Фев. 1, 2025

Язык: Английский