Parity-Dependent Hemosiderin and Lipofuscin Accumulation in the Reproductively Aged Mouse Ovary

The progressive decline of the ovarian follicle pool leads to reproductive ageing. The latter is accompanied by age-related disorders, including various types of cancer. In fact, the highest rates of ovarian cancer (OC) occur at postmenopause while OC risk is significantly modulated by parity records during previous fertile life. We approached the age-parity relationship in the C57BL/6 mouse model and herein describe the presence of nonheme iron (hemosiderin) and deposits of the “age pigment” lipofuscin in reproductively aged mouse ovaries by applying conventional histochemical methods and autofluorescence. In addition, the 8-OHdG adduct was evaluated in ovarian genomic DNA. Both hemosiderin and lipofuscin were significantly higher in virgin compared to multiparous ovaries. The same pattern was observed for 8-OHdG. We conclude that nulliparity induces a long-term accumulation of iron and lipofuscin with concomitant oxidative damage to DNA in the mouse ovary. Since lipofuscin is a widely accepted senescence marker and given the recently postulated role of lipofuscin-associated iron as a source of reactive oxygen species (ROS) in senescent cells, these findings suggest a possible pathogenic mechanism by which nulliparity contributes to an increased OC risk in the postmenopausal ovary.

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Beneficial Role of Phytochemicals on Oxidative Stress and Age-Related Diseases

BioMed Research International ◽

10.1155/2019/8748253 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 56

Author(s):

Cinzia Forni ◽

Francesco Facchiano ◽

Manuela Bartoli ◽

Stefano Pieretti ◽

Antonio Facchiano ◽

...

Keyword(s):

Oxidative Stress ◽

Morphological Changes ◽

Antioxidant Defenses ◽

Oxygen Species ◽

Protective Effects ◽

Biological Functions ◽

Progressive Decline ◽

Age Related ◽

Oxidative Damage To Dna

Aging is related to a number of functional and morphological changes leading to progressive decline of the biological functions of an organism. Reactive Oxygen Species (ROS), released by several endogenous and exogenous processes, may cause important oxidative damage to DNA, proteins, and lipids, leading to important cellular dysfunctions. The imbalance between ROS production and antioxidant defenses brings to oxidative stress conditions and, related to accumulation of ROS, aging-associated diseases. The purpose of this review is to provide an overview of the most relevant data reported in literature on the natural compounds, mainly phytochemicals, with antioxidant activity and their potential protective effects on age-related diseases such as metabolic syndrome, diabetes, cardiovascular disease, cancer, neurodegenerative disease, and chronic inflammation, and possibly lower side effects, when compared to other drugs.

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Regular and Moderate Exercise Counteracts the Decline of Antioxidant Protection but Not Methylglyoxal-Dependent Glycative Burden in the Ovary of Reproductively Aging Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3837623 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 9

Author(s):

S. Falone ◽

S. Jr Santini ◽

V. Cordone ◽

M. Grannonico ◽

M. Cacchio ◽

...

Keyword(s):

Healthy Aging ◽

Molecular Mechanisms ◽

Population Aging ◽

Oxygen Species ◽

Moderate Exercise ◽

Mouse Ovary ◽

Age Related ◽

Age Dependent ◽

Molecular Damage

Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG-) related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS) and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P<0.01), and this was linked to the preservation of the glutathione peroxidase protection against ROS (P<0.001), as well as to the increased glutathione availability (P<0.001). Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P<0.001), exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions.

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Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

Molecular Psychiatry ◽

10.1038/s41380-021-01208-9 ◽

2021 ◽

Author(s):

Sujeong Yang ◽

Sylvain Gigout ◽

Angelo Molinaro ◽

Yuko Naito-Matsui ◽

Sam Hilton ◽

...

Keyword(s):

Chondroitin Sulphate ◽

Memory Loss ◽

Memory Deficits ◽

Long Term Potentiation ◽

Aged Mice ◽

Age Related ◽

Term Potentiation ◽

Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

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Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

International Journal of Molecular Sciences ◽

10.3390/ijms22031296 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1296

Author(s):

Yue Ruan ◽

Subao Jiang ◽

Adrian Gericke

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Vascular Function ◽

Vascular Dysfunction ◽

Therapeutic Strategies ◽

Vision Impairment ◽

Age Related Macular Degeneration ◽

Oxygen Species ◽

Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

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AGE-RELATED DECLINE IN VACCINATION EFFICACY: THE POTENTIAL ROLE OF MYELOID DERIVED SUPPRESSOR CELLS

Успехи геронтологии ◽

10.34922/ae.2020.33.4.023 ◽

2020 ◽

pp. 785-795

Author(s):

Ю. В. Перфильева ◽

Б. В. Каральник ◽

Е. О. Остапчук ◽

А. Кали ◽

Р. Т. Тлеулиева ◽

...

Keyword(s):

Young People ◽

Infectious Diseases ◽

Older People ◽

Suppressor Cells ◽

Primary Response ◽

Myeloid Derived Suppressor Cells ◽

Age Related ◽

Cellular And Humoral Immunity

Инфекционные заболевания у пожилых людей значительно более часты и смертность от них выше, чем у молодых людей. Вакцинация является наиболее эффективной и наименее затратной профилактической мерой при ряде инфекционных заболеваний. Однако вакцины, которые эффективны у молодых людей, часто неэффективны у пожилых людей старше 65 лет, причиной чего является постепенное снижение функциональных возможностей иммунной системы, происходящее с возрастом и называемое иммуностарением. Связанные с возрастом изменения в клеточном и гуморальном иммунитете ухудшают первичный ответ на вакцины и ослабляют развитие долговременной иммунной памяти. Исследования последних лет дают основание предполагать, что одной из возможных причин возникновения и поддержания иммуностарения в организме могут быть миелоидные супрессорные клетки ( Myeloid-Derived Suppressor Cells, MDSC ). Многочисленными исследованиями установлено, что MDSC способны ингибировать функции клеток врожденного и адаптивного иммунитета посредством ряда механизмов. В настоящем обзоре приводятся сведения, подчеркивающие роль MDSC в ингибировании иммунного ответа на вакцины при старении, а также обосновываются возможные пути преодоления данного иммунного препятствия. Infectious diseases in older people are much more frequent, and mortality from them is higher than in young people. Vaccination is the most effective and least expensive preventative measure for a number of infectious diseases. However, vaccines that are effective in young people are often ineffective in older people over 65, which is a result of a gradual decrease in the functional capacity of the immune systems, which occurs with age, and is called «immunosenescence». Age-related changes in the cellular and humoral immunity worsen the primary response to vaccines and weaken the development of long-term immunological memory. Recent studies suggest that one of the possible causes of the occurrence and maintenance of «immunosenescence» may be myeloid-derived suppressor cells ( MDSCs ). These cells have been shown to inhibit the functions of innate and adaptive immunity cells through a number of mechanisms. In this review, we provide information that emphasizes the role of MDSCs in inhibiting the immune response to vaccines during aging, and also substantiates possible ways to overcome this immunological obstacle.

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Long-term macrolide antibiotics in asthma therapy

Reviews in Health Care ◽

10.7175/rhc.v2i4.61 ◽

2011 ◽

Vol 2 (4) ◽

pp. 243-258

Author(s):

Daisuke Takekoshi ◽

Patrick Belvitch ◽

Israel Rubinstein

Keyword(s):

Clinical Trials ◽

Antimicrobial Properties ◽

Inflammatory Cells ◽

Macrolide Antibiotics ◽

Oxygen Species ◽

Immunomodulatory Effects ◽

Diffuse Panbronchiolitis ◽

Heterogeneous Nature

Macrolide antibiotics drew worldwide attention when their use was dramatically successful in the treatment of diffuse panbronchiolitis in 1980s. The success was attributed to their immunomodulatory effects, rather than their antimicrobial properties. Since then, studies have shown that macrolides exert their immunomodulatory effects through several mechanisms, including suppression of proinflammatory cytokines, promoting apoptosis of inflammatory cells, improving phagocytic function, ameliorating airway hypersecretion, and inhibiting production of reactive oxygen species. Macrolides have also been studied in the treatment of asthma. This review highlights the role of macrolides in the treatment of asthma, presenting an overview of the main clinical trials. Despite favourable preclinical data and reports of anecdotal successes, the results of clinical trials are conflicting. This may be due to the heterogeneous nature of asthma. Further studies are needed to identify particular subgroup of asthma that will respond to macrolides.

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LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.631835 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuting Zhuang ◽

Tingting Li ◽

Hongwen Xiao ◽

Jiaxu Wu ◽

Shuang Su ◽

...

Keyword(s):

Molecular Mechanism ◽

Noncoding Rna ◽

Physiological Function ◽

Luciferase Reporter ◽

Aged Mouse ◽

Progressive Decline ◽

Downstream Target ◽

Novel Target ◽

Related Proteins

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored.Methods: Senescence-associated β-galactosidases (SA-β-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism.Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-β-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence.Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.

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Dietary fatty acids and lipoproteins on progression of age-related macular degeneration

Grasas y Aceites ◽

10.3989/gya.0830162 ◽

2017 ◽

Vol 68 (2) ◽

pp. 187 ◽

Cited By ~ 1

Author(s):

S. Montserrat-de la Paz ◽

M. C. Naranjo ◽

B. Bermúdez ◽

S. López ◽

R. Abia ◽

...

Keyword(s):

Fatty Acids ◽

Macular Degeneration ◽

Medical Condition ◽

Dietary Fatty Acids ◽

Age Related Macular Degeneration ◽

Omega 3 ◽

Age Related ◽

Long Chain

Age-related macular degeneration (AMD) is a medical condition of central loss vision and blindness. Numerous studies have revealed that changes on certain dietary fatty acids (FAs) could have useful for AMD management. This review summarizes the effects of dietary omega-3 long-chain PUFAs, MUFAs, and SFAs, and lipoproteins on AMD. Findings are consistent with the beneficial role of dietary omega-3 long-chain PUFAs, while the effects of dietary MUFAs and SFAs appeared to be ambiguous with respect to the possible protection from MUFAs and to the possible adverse impact from SFAs on AMD. Some of the pathological mechanisms associated with lipoproteins on AMD share those observed previously in cardiovascular diseases. It was also noticed that the effects of FAs in the diet and lipoprotein on AMD could be modulated by genetic variants. From a population health perspective, the findings of this review are in favour of omega-3 long-chain FAs recommendations in a preventive and therapeutic regimen to attain lower AMD occurrence and progression rates. Additional long-term and short-term nutrigenomic studies are required to clearly establish the role and the relevance of interaction of dietary FAs, lipoproteins, and genes in the genesis and progression of AMD.

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Mitochondria and Aging—The Role of Exercise as a Countermeasure

Biology ◽

10.3390/biology8020040 ◽

2019 ◽

Vol 8 (2) ◽

pp. 40 ◽

Cited By ~ 17

Author(s):

Mats I Nilsson ◽

Mark A Tarnopolsky

Keyword(s):

Reactive Oxygen Species Generation ◽

Biological Aging ◽

Primary Role ◽

Oxygen Species ◽

Vicious Cycle ◽

Life And Death ◽

Cell Functions ◽

Age Related ◽

Damage Protein

Mitochondria orchestrate the life and death of most eukaryotic cells by virtue of their ability to supply adenosine triphosphate from aerobic respiration for growth, development, and maintenance of the ‘physiologic reserve’. Although their double-membrane structure and primary role as ‘powerhouses of the cell’ have essentially remained the same for ~2 billion years, they have evolved to regulate other cell functions that contribute to the aging process, such as reactive oxygen species generation, inflammation, senescence, and apoptosis. Biological aging is characterized by buildup of intracellular debris (e.g., oxidative damage, protein aggregates, and lipofuscin), which fuels a ‘vicious cycle’ of cell/DNA danger response activation (CDR and DDR, respectively), chronic inflammation (‘inflammaging’), and progressive cell deterioration. Therapeutic options that coordinately mitigate age-related declines in mitochondria and organelles involved in quality control, repair, and recycling are therefore highly desirable. Rejuvenation by exercise is a non-pharmacological approach that targets all the major hallmarks of aging and extends both health- and lifespan in modern humans.

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