Probiotic supplementation attenuates age‐related sarcopenia via the gut–muscle axis in SAMP8 mice

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.

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Senescent Accelerated Prone 8 (SAMP8) Mice as A Model of Age Dependent Neuroinflammation

10.21203/rs.3.rs-72160/v1 ◽

2020 ◽

Author(s):

Andrés Fernández ◽

Elena Quintana ◽

Patricia Velasco ◽

Belén de Andrés ◽

Maria Luisa Gaspar ◽

...

Keyword(s):

Choroid Plexus ◽

Inflammatory Cytokines ◽

Hippocampal Formation ◽

Morphological Changes ◽

Interleukin 1 ◽

Brain Parenchyma ◽

Age Related ◽

Inflammatory Changes ◽

Samp8 Mice ◽

The Brain

Abstract Background: Aging and age related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). The need of animal models that will allow us to understand and modulate this process is required for the scientific community. Methods: We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their resistant to senescence control (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and analyzed Iba1+ clustered cells with aging. To analyse specific constant brain areas we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus and meningeal membranes (m/Ch), and analyzed their response to systemic LPS- driven inflammation.Results: Aged 10 month old SAMP8 mice presents many of the hallmarks of aging-dependent neuroinflammation when compared with their senescence resistant control (SAMR1); ie, increase of protein aggregates, presence of Iba1+ clusters, but not increase in the number of Iba1+ cells. We have further observed and increased of main inflammatory mediator IL-1β, and augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus and meningeal membranes (m/Ch) have been analyzed showing that there is not significant increase of CD45+ from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL1β) transcription is mainly enhanced in CD45+BP cells. Furthermore, we are showing that LPS-driven systemic inflammation produces inflammatory cytokines mainly in the border bMyC, sensed to a lesser extent by the BP bMyC, and is enhanced in aged SAMP8 compared to control SAMR1.Conclusion: Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of main pro inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.

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The Antioxidant Resveratrol from Polygonum Cuspidatum Reverses Memory Impairment and Brain Oxidative Stress in SAMP8 Mice

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.422.470 ◽

2011 ◽

Vol 422 ◽

pp. 470-473

Author(s):

Gui Shan Liu ◽

Ze Sheng Zhang ◽

Bo Yang ◽

Wei He

Keyword(s):

Oxidative Stress ◽

Learning And Memory ◽

Open Field ◽

Field Test ◽

Memory Impairment ◽

Open Field Test ◽

Pharmacological Action ◽

Age Related ◽

Brain Oxidative Stress ◽

Samp8 Mice

Resveratrol (RVT) is a phytoalexin polyphenolic compound found in various plants, including grapes, berries and peanuts. Recently, studies have documented various health benefits of resveratrol including cardiovascular and cancer-chemopreventive properties. The aim of the present study was to demonstrate the effects of resveratrol on the learning and memory impairment. The senescence-accelerated mice (SAM) were introgastric gavage administrated resveratrol (25,100mg/(kg•bw)) for 60 days. The learning and memory behavior was assessed using open-field test while the parameters of oxidative stress assessed were malondialdehyde (MDA) and superoxide dismutases (SOD).The results showed that resveratrol significantly improved the learning and memory ability in open-field test. Further investigation showed that resveratrol restored SOD levels, but decreased MDA level in the mouce brain. These results indicated that the pharmacological action of RVT may offer a novel therapeutic strategy for the treatment of age-related conditions.

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Effects of moderate exercise over different phases on age-related physiological dysfunction in testes of SAMP8 mice

Experimental Gerontology ◽

10.1016/j.exger.2013.05.063 ◽

2013 ◽

Vol 48 (9) ◽

pp. 869-880 ◽

Cited By ~ 27

Author(s):

Xiujun Zhao ◽

Yanqing Bian ◽

Yichong Sun ◽

Li Li ◽

Lixuan Wang ◽

...

Keyword(s):

Moderate Exercise ◽

Age Related ◽

Samp8 Mice

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Lactobacillus paracasei PS23 decelerated age-related muscle loss by ensuring mitochondrial function in SAMP8 mice

Aging ◽

10.18632/aging.101782 ◽

2019 ◽

Vol 11 (2) ◽

pp. 756-770 ◽

Cited By ~ 3

Author(s):

Li-Han Chen ◽

Shih-Yi Huang ◽

Kuo-Chin Huang ◽

Chih-Chieh Hsu ◽

Kuen-Cheh Yang ◽

...

Keyword(s):

Mitochondrial Function ◽

Lactobacillus Paracasei ◽

Muscle Loss ◽

Age Related ◽

Samp8 Mice

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Long-Term Feeding of a High-Fat Diet Ameliorated Age-Related Phenotypes in SAMP8 Mice

Nutrients ◽

10.3390/nu12051416 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1416

Author(s):

Hideaki Oike ◽

Yukino Ogawa ◽

Kayo Azami

Keyword(s):

Control Diet ◽

Active Phase ◽

Restricted Feeding ◽

Long Term Effects ◽

High Fat ◽

Night Time ◽

Age Related ◽

Nutritional Studies ◽

Samp8 Mice

High-fat diets (HFD) have been thought to increase the risk of obesity and metabolic syndrome, as well as shorten lifespan. On the other hand, chrono-nutritional studies have shown that time-restricted feeding during active phase significantly suppresses the induction of HFD-induced obesity in mouse model. However, the long-term effects of time-restricted HFD feeding on aging are unknown. Therefore, in this study, we set up a total of four groups: mutual combination of ad libitum feeding or night-time-restricted feeding (NtRF) and an HFD or a control diet. We examined their long-term effects in a senescence-accelerated mouse strain, SAMP8, for over a year. Hearing ability, cognitive function, and other behavioral and physiological indexes were evaluated during the study. Unexpectedly, SAMP8 mice did not show early onset of death caused by the prolonged HFD intake, and both HFD and NtRF retarded age-related hearing loss (AHL). NtRF improved grip strength and cognitive memory scores, while HFD weakly suppressed age-related worsening of the appearance scores associated with the eyes. Notably, the HFD also retarded the progression of AHL in both DBA/2J and C57BL/6J mice. These results suggest that HFD prevents aging unless metabolic disorders occur and that HFD and NtRF are independently effective in retarding aging; thus, the combination of HFD and chrono-nutritional feeding may be an effective anti-aging strategy.

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3,4-Dihydroxybenzalacetone (DBL) Prevents Aging-Induced Myocardial Changes in Senescence-Accelerated Mouse-Prone 8 (SAMP8) Mice

Cells ◽

10.3390/cells9030597 ◽

2020 ◽

Vol 9 (3) ◽

pp. 597

Author(s):

Vijayasree V. Giridharan ◽

Vengadeshprabhu Karupppagounder ◽

Somasundaram Arumugam ◽

Yutaka Nakamura ◽

Ashrith Guha ◽

...

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

Cardiac Fibrosis ◽

Myocardial Dysfunction ◽

The Elderly ◽

Tunel Staining ◽

Inonotus Obliquus ◽

Age Related ◽

Samp8 Mice ◽

Senescence Accelerated Mouse

Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotus obliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.

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Lactobacillus paracasei PS23 Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice

Nutrients ◽

10.3390/nu10070894 ◽

2018 ◽

Vol 10 (7) ◽

pp. 894 ◽

Cited By ~ 12

Author(s):

Shih-Yi Huang ◽

Li-Han Chen ◽

Ming-Fu Wang ◽

Chih-Chieh Hsu ◽

Ching-Hung Chan ◽

...

Keyword(s):

Cognitive Decline ◽

Brain Dysfunction ◽

Lactobacillus Paracasei ◽

Oxidative Enzymes ◽

Control Group ◽

Age Related ◽

Chemotactic Protein ◽

Age Related Cognitive Decline ◽

Samp8 Mice ◽

Senescence Accelerated Mouse

Probiotic supplements are potential therapeutic agents for age-related disorders due to their antioxidant and anti-inflammatory properties. However, the effect of probiotics on age-related brain dysfunction remains unclear. To investigate the effects of Lactobacillus paracasei PS23 (LPPS23) on the progression of age-related cognitive decline, male and female senescence-accelerated mouse prone 8 (SAMP8) mice were divided into two groups (n = 6 each): the control and PS23 groups. From the age of 16 weeks, these groups were given saline and LPPS23, respectively, because SAMP8 mice start aging rapidly after four months of age. After 12 weeks of treatment, we evaluated the effect of LPPS23 by analyzing their appearance, behavior, neural monoamines, anti-oxidative enzymes, and inflammatory cytokines. The PS23 group showed lower scores of senescence and less serious anxiety-like behaviors and memory impairment compared to the control group. The control mice also showed lower levels of neural monoamines in the striatum, hippocampus, and serum. Moreover, LPPS23 induced the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Higher levels of tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP1) and lower levels of interleukin (IL)-10 indicated that LPPS23 modulated the inflammation. Our results suggest that LPPS23 supplements could delay age-related cognitive decline, possibly by preventing oxidation and inflammation and modulating gut–brain axis communication.

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