Ovarian aging in humans: potential strategies for extending reproductive lifespan

Cavalcante, Marcelo Borges; Sampaio, Olga Goiana Martins; Câmara, Fernanda Eunice Araújo; Schneider, Augusto; Ávila, Bianca Machado de; Prosczek, Juliane B.; Masternak, Michał M.; Campos, Adriana Rolim

doi:10.1007/s11357-023-00768-8

Cited by 28 publications

(5 citation statements)

References 131 publications

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“…In human females, the peak of ovarian follicular count is achieved during intrauterine development around the 20th week of gestation, with a recorded count of about 6-7 million follicles. During the second half of fetal life, follicles undergo apoptosis, leaving this number at only 1-2 million and 300,000-400,000 at birth and menarche, respectively [25][26][27]. The number of follicles that reach the ovulation stage throughout a woman's reproductive lifespan is approximately 400-500, one percent of the total follicular pool [28,29].…”

Section: Factors Contributing To Ovarian Agingmentioning

confidence: 99%

“…A diminishing ovarian follicle pool dictates critical reproductive processes, such as a decline in fecundity, infertility, irregular menstrual cycles, and ultimately menopause around the age of 51, with only about 1000 follicles remaining in the ovaries [25][26][27]. The chapter of the ovarian lifespan concludes when the once-robust pool of ovarian reserve diminishes to a critical threshold with advanced age.…”

Section: Factors Contributing To Ovarian Agingmentioning

confidence: 99%

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A Molecular Perspective and Role of NAD+ in Ovarian Aging

Ahmed,

Riaz,

et al. 2024

IJMS

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The decline in female fecundity is linked to advancing chronological age. The ovarian reserve diminishes in quantity and quality as women age, impacting reproductive efficiency and the aging process in the rest of the body. NAD+ is an essential coenzyme in cellular energy production, metabolism, cell signaling, and survival. It is involved in aging and is linked to various age-related conditions. Hallmarks associated with aging, diseases, and metabolic dysfunctions can significantly affect fertility by disturbing the delicate relationship between energy metabolism and female reproduction. Enzymes such as sirtuins, PARPs, and CD38 play essential roles in NAD+ biology, which actively consume NAD+ in their enzymatic activities. In recent years, NAD+ has gained much attention for its role in aging and age-related diseases like cancer, Alzheimer’s, cardiovascular diseases, and neurodegenerative disorders, highlighting its involvement in various pathophysiological processes. However, its impact on female reproduction is not well understood. This review aims to bridge this knowledge gap by comprehensively exploring the complex interplay between NAD+ biology and female reproductive aging and providing valuable information that could help develop plans to improve women’s reproductive health and prevent fertility issues.

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Section: Factors Contributing To Ovarian Agingmentioning

confidence: 99%

Section: Factors Contributing To Ovarian Agingmentioning

confidence: 99%

A Molecular Perspective and Role of NAD+ in Ovarian Aging

Ahmed,

Riaz,

et al. 2024

IJMS

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“…The ovaries are more susceptible to the effects of natural ageing than other organs and tissues, making ovarian ageing an urgent clinical issue to be addressed. Treatments for ovarian ageing include growth hormone therapy, antioxidant supplements such as melatonin and vitamin C, mitochondrial therapy, and personalized treatments tailored to each patient with their special fertility problems [11][12][13]. MSC therapy, as a new antiageing therapy, is currently in the preliminary stage of clinical application in the human ovary [14,15].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model

Pei,

Fu,

Guo

et al. 2024

Stem Cell Res Ther

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Background Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. Methods Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. Results After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. Conclusions Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

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“…Reproductive aging entails the gradual and continuous decline of ovarian reserve until its exhaustion and the onset of menopause (Broekmans et al, 2009; Finch, 2014; Cavalcante et al, 2023). Menopause results in decreased estrogen levels, leading to metabolic changes such as increased body weight gain, adiposity and dyslipidemia, increasing the risk of chronic diseases (Selbac et al, 2018; Bitto et al, 2009; Lizcano and Guzmán, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effect of senolytic drugs in young female mice chemically induced to estropause

Ávila,

Zanini,

Luduvico

et al. 2024

Preprint

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Aims: This study aimed to assess metabolic responses and senescent cell burden in young female mice induced to estropause and treated with senolytic drugs. Main methods: Estropause was induced by 4-vinylcyclohexene diepoxide (VCD) injection in two-month-old mice. The senolytics dasatinib and quercetin (D+Q) or fisetin were given by oral gavage once a month from five to 11 months of age. Key findings: VCD-induced estropause led to increased body mass and reduced albumin concentrations compared to untreated cyclic mice, without affecting insulin sensitivity, lipid profile, liver enzymes, or total proteins. Estropause decreased catalase activity in adipose tissue but had no significant effect on other redox parameters in adipose and hepatic tissues. Fisetin treatment reduced ROS levels in the hepatic tissue of estropause mice. Estropause did not influence senescence-associated beta-galactosidase activity in adipose and hepatic tissues, but increased senescent cell markers and fibrosis in ovaries. Senolytic treatment did not decrease ovarian cellular senescence induced by estropause. Significance: Overall, the findings suggest that estropause leads to minor metabolic changes in young females, and senolytics had no protective effects despite increased ovarian senescence.

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Ovarian aging in humans: potential strategies for extending reproductive lifespan

Cited by 28 publications

References 131 publications

A Molecular Perspective and Role of NAD+ in Ovarian Aging

A Molecular Perspective and Role of NAD+ in Ovarian Aging

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model

Effect of senolytic drugs in young female mice chemically induced to estropause

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