News | Scientists Uncover Ovarian Aging Mechanisms; Pioneering Molecular Atlas Advances Fertility and Healthy Longevity Research
In a recent study, scientists from several U.S. research institutions used advanced single-nucleus multiomics to reveal biological mechanisms of ovarian aging. By comparing the molecular and genetic features of ovaries from younger women aged 23-29 and reproductively aged women aged 49-54, the study mapped age-related changes in gene expression and chromatin accessibility across all major ovarian cell types, including follicular granulosa cells, ovarian endothelial cells, and stromal cells, and identified new biomarkers of ovarian aging.
Published in Nature Aging, the study identified 3455 differentially expressed genes (DEGs) associated with ovarian aging, including RICTOR, MAP3K5, IGF1R, and APOE. It also found functional noncoding regulatory variants and transcription factors such as CEBPD whose importance in ovarian aging had not previously been recognized. The study particularly highlighted the mTOR signaling pathway as an ovary-specific aging pathway with potential therapeutic relevance for delaying ovarian aging.
By integrating genome-wide association study (GWAS) data, the team created and publicly released a detailed molecular atlas of ovarian aging. It will support future aging research, particularly work on fertility preservation and age-related health interventions.
Background: Biological Markers of Ovarian Aging
The ovaries are two glands in the female reproductive system that produce eggs and hormones essential to fertility. They are among the first human tissues affected by aging, with a gradual decline in oocyte number and quality. Research indicates that ovarian aging accelerates markedly around age 37, substantially increasing the risk of infertility and chromosomal abnormalities.
Genomic studies have shown that ovarian aging is strongly influenced by genetics, supported by variation in age at natural menopause (ANM) between twins. Traditional molecular methods, however, have lacked enough detail to fully explain these mechanisms. Using single-nucleus multiomics, the new study precisely mapped changes in chromatin accessibility and gene expression during ovarian aging, addressing an important research gap.
Methods: Multiomics Reveals the Molecular Basis of Ovarian Aging
The researchers used single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) to analyze 8 cryopreserved human ovarian samples from younger women aged 23-29 and reproductively aged women aged 49-54. These high-throughput techniques enabled them to map chromatin accessibility and transcriptional profiles for each ovarian cell type and identify highly coordinated age-related changes in gene expression.
Unlike cells in other organs, ovarian cells showed strongly coordinated gene expression during aging, suggesting that ovarian aging is highly synchronized. Significant changes appeared across cell types such as granulosa and ovarian endothelial cells, with most aging-related gene expression changes occurring in granulosa cells.
Key Finding: mTOR Signaling as a New Marker of Ovarian Aging
The results indicate that mTOR signaling plays a central role in ovarian aging and may be an ovary-specific aging pathway. It may therefore represent a potential therapeutic target for delaying ovarian aging and improving fertility preservation. Most functional variants identified during ovarian aging occurred in noncoding regions, providing a new direction for interventions targeting these regions.
Using the CellChat platform, the team also found that communication among granulosa cells, ovarian endothelial cells, and oocytes declined significantly with age. Researchers noted that this may be closely related to age-associated loss of ovarian function and could inform development of therapies targeting specific cell types.
Conclusion: A Foundation for Ovarian Aging Research
The study provides important insight into the molecular, cellular, and genetic basis of human ovarian aging. Its detailed atlas offers researchers a resource on age-related cell types and key genes. The findings provide a theoretical basis for interventions targeting mTOR and other aging pathways and advance research on delaying ovarian aging and preserving fertility.
This work represents important progress toward delaying or even reversing ovarian aging and may offer new ways to improve fertility and reduce age-related health problems.
News | Scientists Uncover Ovarian Aging Mechanisms; Pioneering Molecular Atlas Advances Fertility and Healthy Longevity Research
News | Scientists Uncover Ovarian Aging Mechanisms; Pioneering Molecular Atlas Advances Fertility and Healthy Longevity Research
In a recent study, scientists from several U.S. research institutions used advanced single-nucleus multiomics to reveal biological mechanisms of ovarian aging. By comparing the molecular and genetic features of ovaries from younger women aged 23-29 and reproductively aged women aged 49-54, the study mapped age-related changes in gene expression and chromatin accessibility across all major ovarian cell types, including follicular granulosa cells, ovarian endothelial cells, and stromal cells, and identified new biomarkers of ovarian aging.
Published in Nature Aging, the study identified 3455 differentially expressed genes (DEGs) associated with ovarian aging, including RICTOR, MAP3K5, IGF1R, and APOE. It also found functional noncoding regulatory variants and transcription factors such as CEBPD whose importance in ovarian aging had not previously been recognized. The study particularly highlighted the mTOR signaling pathway as an ovary-specific aging pathway with potential therapeutic relevance for delaying ovarian aging.
By integrating genome-wide association study (GWAS) data, the team created and publicly released a detailed molecular atlas of ovarian aging. It will support future aging research, particularly work on fertility preservation and age-related health interventions.
Background: Biological Markers of Ovarian Aging
The ovaries are two glands in the female reproductive system that produce eggs and hormones essential to fertility. They are among the first human tissues affected by aging, with a gradual decline in oocyte number and quality. Research indicates that ovarian aging accelerates markedly around age 37, substantially increasing the risk of infertility and chromosomal abnormalities.
Genomic studies have shown that ovarian aging is strongly influenced by genetics, supported by variation in age at natural menopause (ANM) between twins. Traditional molecular methods, however, have lacked enough detail to fully explain these mechanisms. Using single-nucleus multiomics, the new study precisely mapped changes in chromatin accessibility and gene expression during ovarian aging, addressing an important research gap.
Methods: Multiomics Reveals the Molecular Basis of Ovarian Aging
The researchers used single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) to analyze 8 cryopreserved human ovarian samples from younger women aged 23-29 and reproductively aged women aged 49-54. These high-throughput techniques enabled them to map chromatin accessibility and transcriptional profiles for each ovarian cell type and identify highly coordinated age-related changes in gene expression.
Unlike cells in other organs, ovarian cells showed strongly coordinated gene expression during aging, suggesting that ovarian aging is highly synchronized. Significant changes appeared across cell types such as granulosa and ovarian endothelial cells, with most aging-related gene expression changes occurring in granulosa cells.
Key Finding: mTOR Signaling as a New Marker of Ovarian Aging
The results indicate that mTOR signaling plays a central role in ovarian aging and may be an ovary-specific aging pathway. It may therefore represent a potential therapeutic target for delaying ovarian aging and improving fertility preservation. Most functional variants identified during ovarian aging occurred in noncoding regions, providing a new direction for interventions targeting these regions.
Using the CellChat platform, the team also found that communication among granulosa cells, ovarian endothelial cells, and oocytes declined significantly with age. Researchers noted that this may be closely related to age-associated loss of ovarian function and could inform development of therapies targeting specific cell types.
Conclusion: A Foundation for Ovarian Aging Research
The study provides important insight into the molecular, cellular, and genetic basis of human ovarian aging. Its detailed atlas offers researchers a resource on age-related cell types and key genes. The findings provide a theoretical basis for interventions targeting mTOR and other aging pathways and advance research on delaying ovarian aging and preserving fertility.
This work represents important progress toward delaying or even reversing ovarian aging and may offer new ways to improve fertility and reduce age-related health problems.
Source:
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