Oogenesis Arrest Prior to Birth: A Trade-off between Possible Evolutionary Advantages and Age-Related Oocyte Dysfunction?

Oogenesis in mammalian females, including humans, is arrested prior to birth. Females, therefore, are born with a limited number of primary oocytes. This is in direct contrast to males in whom spermatogenesis continues during the entire lifespan following puberty. Here, we discuss possible evolutionary advantages that this confers and contrast this with age-related decline in oocyte quality that results in diminished fertility with advancing maternal age. We believe that a better understanding of these processes would be helpful in developing strategies to preserve fertility as maternal age increases, especially in the context of the current demographic shift with more and more women seeking fertility treatment at advanced age.

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Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos

International Journal of Molecular Sciences ◽

10.3390/ijms22105327 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5327

Author(s):

Lianguang Xu ◽

Muhammad Idrees ◽

Myeong-Don Joo ◽

Tabinda Sidrat ◽

Yiran Wei ◽

...

Keyword(s):

Granulosa Cells ◽

Constitutive Expression ◽

Growth Factor Receptor ◽

Oocyte Quality ◽

Low Fertility ◽

Treatment Groups ◽

Age Related ◽

Early Embryos ◽

Plasmid Injection ◽

Telomere Lengthening

Age-associated decline in oocyte quality is one of the dominant factors of low fertility. Aging alters several key processes, such as telomere lengthening, cell senescence, and cellular longevity of granulosa cells surrounding oocyte. To investigate the age-dependent molecular changes, we examined the expression, localization, and correlation of telomerase reverse transcriptase (TERT) and β-Klotho (KLB) in bovine granulosa cells, oocytes, and early embryos during the aging process. Herein, cumulus-oocyte complexes (COCs) obtained from aged cows (>120 months) via ovum pick-up (OPU) showed reduced expression of β-Klotho and its co-receptor fibroblast growth factor receptor 1 (FGFR1). TERT plasmid injection into pronuclear zygotes not only markedly enhanced day-8 blastocysts’ development competence (39.1 ± 0.8%) compared to the control (31.1 ± 0.5%) and D-galactose (17.9 ± 1.0%) treatment groups but also enhanced KLB and FGFR1 expression. In addition, plasmid-injected zygotes displayed a considerable enhancement in blastocyst quality and implantation potential. Cycloastragenol (CAG), an extract of saponins, stimulates telomerase enzymes and enhances KLB expression and alleviates age-related deterioration in cultured primary bovine granulosa cells. In conclusion, telomerase activation or constitutive expression will increase KLB expression and activate the FGFR1/β-Klotho pathway in bovine granulosa cells and early embryos, inhibiting age-related malfunctioning.

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Antioxidant activities and lipid peroxidation status in human follicular fluid: age-dependent change

Zygote ◽

10.1017/s0967199421000241 ◽

2021 ◽

pp. 1-5

Author(s):

H. Debbarh ◽

N. Louanjli ◽

S. Aboulmaouahib ◽

M. Jamil ◽

L. Ahbbas ◽

...

Keyword(s):

Lipid Peroxidation ◽

Follicular Fluid ◽

Maternal Age ◽

Antioxidant Activities ◽

Human Follicular Fluid ◽

Age Related ◽

Group I ◽

Group Ii ◽

Scavenging Efficiency

Summary Maternal age is a significant factor influencing in vitro fertilization (IVF) outcomes. Oxidative stress (OS) is one of the major causes of age-related cellular and molecular damage. The purpose of this work was to investigate the correlation between maternal age with intrafollicular antioxidants and OS markers in follicular fluid (FF), and also to determine the OS status in patients of advanced age. This study was a prospective study including 201 women undergoing IVF whose age was between 24 and 45 years old. FF samples were obtained from mature follicles at the time of oocyte retrieval. After treatment of FF, lipid peroxidation levels (MDA) and enzyme activities such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione (GSH) level were evaluated using spectrophotometry. The results indicated that the age cutoff point for increasing the MDA level was fixed at 37 years, allowing the study to be differentiated into two age groups. Group I included patients whose age was less than 37 years, and group II included patients whose age was greater than or equal 37 years. Statistical analysis revealed that MDA and GSH levels and GR activity were significantly higher in group II compared with group I. The SOD and CAT activities were significantly less in group II compared with group I. We concluded that from 37 years old a reproductive ageing was accompanied by a change in the antioxidant pattern in FF that impaired reactive oxygen species scavenging efficiency.

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Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

Journal of Clinical Medicine ◽

10.3390/jcm10153243 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3243

Author(s):

Rita Del Pinto ◽

Davide Grassi ◽

Raffaella Bocale ◽

Francesco Carubbi ◽

Claudio Ferri ◽

...

Keyword(s):

Cognitive Impairment ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Demographic Shift ◽

Antihypertensive Medications ◽

Microvascular Damage ◽

Middle Way ◽

Alzheimer Type Dementia ◽

Age Related ◽

Pressure Profiles

With the demographic shift toward advanced ages, it is imperative to understand the biological mechanisms behind common, disabling age-related diseases such as cognitive impairment in its mild form to overt dementia. Hypertension, a major cardiovascular risk factor, is epidemiologically linked to vascular and Alzheimer-type dementia, with possible mechanisms being atherosclerotic macro- and microvascular damage leading to neuronal cell death, as well as proinflammatory events responsible for neurodegeneration. Nevertheless, there is currently a knowledge gap as to which population to target, what the diagnostics test, and how to manage early pathogenic events in order to prevent such a dramatic and disabling condition. While clinical trials data support the benefit of active BP control with antihypertensive medications on the risk of future cognitive impairment, hypotension appears to be related to accelerated cognitive decline in both the fit and the cognitively frail elderly. Dedicated, technologically advanced studies assessing the relation of BP with dementia are needed to clarify the pathophysiological mechanisms in the association before a tailored preventive, diagnostic, and therapeutic approach to one of the most widespread modern medical challenges becomes a reality.

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Outer retinal tubulation formation and clinical course of advanced age-related macular degeneration

Scientific Reports ◽

10.1038/s41598-021-94310-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alessandro Arrigo ◽

Emanuela Aragona ◽

Ottavia Battaglia ◽

Andrea Saladino ◽

Alessia Amato ◽

...

Keyword(s):

Macular Degeneration ◽

Müller Cells ◽

Geographic Atrophy ◽

Age Related Macular Degeneration ◽

Advanced Age ◽

Age Related ◽

Dry Amd ◽

Foveal Sparing ◽

Wet Amd

AbstractOuter retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3–35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.

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Methylation Marks of Blood Leukocytes of Native Hucul Mares Differentiated in Age

International Journal of Genomics ◽

10.1155/2019/2839614 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

T. Ząbek ◽

E. Semik-Gurgul ◽

T. Szmatoła ◽

A. Gurgul ◽

A. Fornal ◽

...

Keyword(s):

Cancer Progression ◽

Late Onset ◽

Advanced Age ◽

Farm Animals ◽

Blood Leukocytes ◽

Data Set ◽

Reduced Representation ◽

Cellular Signal

Horses are one of the longest-living species of farm animals. Advanced age is often associated with a decrease in body condition, dysfunction of immune system, and late-onset disorders. Due to this, the search for new solutions in the prevention and treatment of pathological conditions of the advanced age of horses is desirable. That is why the identification of aging-related changes in the horse genome is interesting in this respect. In the recent years, the research on aging includes studies of age-related epigenetic effects observed on the DNA methylation level. We applied reduced representation bisulfite sequencing (RRBS) to uncover a range of age DMR sites in genomes of blood leukocytes derived from juvenile and aged horses of native Hucul breed. Genes colocated with age-related differentially methylated regions (age DMRs) are the members of pathways involved in cellular signal transduction, immune response, neurogenesis, differentiation, development, and cancer progression. A positive correlation was found between methylation states and gene expression in particular loci from our data set. Some of described age DMR-linked genes were also reported elsewhere. Obtained results contribute to the knowledge about the molecular basis of aging of equine blood cells.

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Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8+ T cells in aged mice

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1525167113 ◽

2016 ◽

Vol 113 (5) ◽

pp. 1333-1338 ◽

Cited By ~ 30

Author(s):

Kylie M. Quinn ◽

Sophie G. Zaloumis ◽

Tania Cukalac ◽

Wan-Ting Kan ◽

Xavier Y. X. Sng ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Influenza A ◽

Cytotoxic T Lymphocyte ◽

Clonal Diversity ◽

Cell Receptor ◽

Advanced Age ◽

Age Related ◽

Self Recognition ◽

Underlying Mechanisms

In advanced age, decreased CD8+ cytotoxic T-lymphocyte (CTL) responses to novel pathogens and cancer is paralleled by a decline in the number and function of naïve CTL precursors (CTLp). Although the age-related fall in CD8+ T-cell numbers is well established, neither the underlying mechanisms nor the extent of variation for different epitope specificities have been defined. Furthermore, naïve CD8+ T cells expressing high levels of CD44 accumulate with age, but it is unknown whether this accumulation reflects their preferential survival or an age-dependent driver of CD8+ T-cell proliferation. Here, we track the number and phenotype of four influenza A virus (IAV)-specific CTLp populations in naïve C57BL/6 (B6) mice during aging, and compare T-cell receptor (TCR) clonal diversity for the CD44hi and CD44lo subsets of one such population. We show differential onset of decline for several IAV-specific CD8+ T-cell populations with advanced age that parallel age-associated changes in the B6 immunodominance hierarchy, suggestive of distinct impacts of aging on different epitope-specific populations. Despite finding no evidence of clonal expansions in an aged, epitope-specific TCR repertoire, nonrandom alterations in TCR usage were observed, along with elevated CD5 and CD8 coreceptor expression. Collectively, these data demonstrate that naïve CD8+ T cells expressing markers of heightened self-recognition are selectively retained, but not clonally expanded, during aging.

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A Risk Score for the Prediction of Advanced Age-Related Macular Degeneration

Ophthalmology ◽

10.1016/j.ophtha.2014.01.016 ◽

2014 ◽

Vol 121 (7) ◽

pp. 1421-1427 ◽

Cited By ~ 15

Author(s):

Chung-Jung Chiu ◽

Paul Mitchell ◽

Ronald Klein ◽

Barbara E. Klein ◽

Min-Lee Chang ◽

...

Keyword(s):

Macular Degeneration ◽

Risk Score ◽

Age Related Macular Degeneration ◽

Advanced Age ◽

Age Related

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Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4015874 ◽

2017 ◽

Vol 2017 ◽

pp. 1-22 ◽

Cited By ~ 25

Author(s):

Bettina P. Mihalas ◽

Kate A. Redgrove ◽

Eileen A. McLaughlin ◽

Brett Nixon

Keyword(s):

Oxidative Damage ◽

Molecular Mechanisms ◽

Spindle Assembly Checkpoint ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Oocyte Quality ◽

Protein Repair ◽

Protective Mechanisms ◽

Pronounced Increase ◽

Age Related

In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte.

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