Unraveling the mode of action of medicinal plants in delaying age-related diseases using model organisms

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

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Abstract 426: Laminin Downregulation Facilitates Cardiomyocyte Coupling in situ to Increase Contractile Function

Circulation Research ◽

10.1161/res.119.suppl_1.426 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Ayla Sessions ◽

Gaurav Kaushik ◽

Adam Engler

Keyword(s):

Basement Membrane ◽

Contractile Function ◽

Current Model ◽

Model Systems ◽

Model Organisms ◽

Muscle Physiology ◽

Heart Tube ◽

Age Related ◽

New Evidence

Aging is associated with extensive remodeling of the heart, including basement membrane extracellular matrix (ECM) components that surround cardiomyocytes. Remodeling is thought to contribute to impaired cardiac mechanotransduction, but the contribution of specific basement membrane ECM components to age-related cardiac remodeling is unclear, owing to current model systems being complex and slow to age. To investigate the effect of basement membrane remodeling on mechanical function in genetically tractable, rapidly aging, and simple model organisms, we employed Drosophila melanogaster, which has a simple trilayered heart tube composed of only basement membrane ECM. We observed differential regulation of collagens between laboratory Drosophila strains , i.e. yellow-white ( yw ) and white-1118 ( w 1118 ), leading to changes in muscle physiology, which were linked to severity of dysfunction with age. Therefore, we sought to understand the extent to which basement membrane ECM modulates lateral cardiomyocyte coupling and contractile function during aging. Cardiac-restricted knockdown of ECM genes Pericardin , Laminin A , and Viking in Drosophila prevented age-associated heart tube restriction and increased contractility, even under viscous load. Most notably, reduction of Laminin A expression decreased levels of other genes that co-assemble in ECM, leading to overall preservation of contractile velocity and extension of median organismal lifespan by 3 weeks or 39%. These data provide new evidence of a direct link between basement membrane ECM homeostasis, contractility, and maintenance of lifespan.

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Impact of nutrition on the ageing process

British Journal Of Nutrition ◽

10.1017/s0007114514003237 ◽

2014 ◽

Vol 113 (S1) ◽

pp. S18-S22 ◽

Cited By ~ 29

Author(s):

John C. Mathers

Keyword(s):

Human Life ◽

Premature Mortality ◽

Later Life ◽

Energy Restriction ◽

Healthy Ageing ◽

Ageing Process ◽

Model Organisms ◽

Nutritional Interventions ◽

Age Related ◽

Reduced Risk

Human life expectancy has been increasing steadily for almost two centuries and is now approximately double what it was at the beginning of the Victorian era. This remarkable demographic change has been accompanied by a shift in disease prevalence so that age is now the major determinant of most common diseases. The challenge is to enhance healthy ageing and to reduce the financial and social burdens associated with chronic ill health in later life. Studies in model organisms have demonstrated that the ageing phenotype arises because of the accumulation of macromolecular damage within the cell and that the ageing process is plastic. Nutritional interventions that reduce such damage, or which enhance the organism's capacity to repair damage, lead to greater longevity and to reduced risk of age-related diseases. Dietary (energy) restriction increases lifespan in several model organisms, but it is uncertain whether it is effective in primates, including humans. However, excess energy storage leading to increased adiposity is a risk factor for premature mortality and for age-related diseases so that obesity prevention is likely to be a major public health route to healthy ageing. In addition, adherence to healthy eating patterns, such as the Mediterranean dietary pattern, is associated with longevity and reduced risk of age-related diseases.

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Reproductive aging: insights from model organisms

Biochemical Society Transactions ◽

10.1042/bst20110694 ◽

2011 ◽

Vol 39 (6) ◽

pp. 1770-1774 ◽

Cited By ~ 1

Author(s):

Alice L. Ye ◽

Needhi Bhalla

Keyword(s):

Nuclear Envelope ◽

Recent Work ◽

Nuclear Organization ◽

Regulatory Control ◽

Model Organisms ◽

Reproductive Aging ◽

Cellular Mechanisms ◽

Age Related ◽

Number Of Factors ◽

Genetic Mechanisms

Aging was once thought to be the result of a general deterioration of tissues as opposed to their being under regulatory control. However, investigations in a number of model organisms have illustrated that aspects of aging are controlled by genetic mechanisms and are potentially manipulable, suggesting the possibility of treatment for age-related disorders. Reproductive decline is one aspect of aging. In model organisms and humans of both sexes, increasing age is associated with both a decline in the number of progeny and an increased incidence of defects. The cellular mechanisms of reproductive aging are not well understood, although a number of factors, both intrinsic and extrinsic to an organism's germline, may contribute to aging phenotypes. Recent work in a variety of organisms suggests that nuclear organization and nuclear envelope proteins may play a role in these processes.

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Herbal Treatments for Age-Related Macular Degeneration: A Literature Review

10.36811/irjo.2020.110005 ◽

2020 ◽

pp. 01-13

Keyword(s):

Risk Factors ◽

Medicinal Plants ◽

Literature Review ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Carnosic Acid ◽

Retinal Diseases ◽

Lycium Barbarum ◽

Age Related ◽

Wide Range

Background and aim: Age-related macular degeneration (AMD) is one of the major causes of blindness and it has risk factors such as obesity, hypertension, smoking, or genetic characteristics. There is no certain cure for AMD till now, so it is very important to design new therapeutic agents or strategies for treatment of AMD. This literature review assessed the effects of different plants or herbal extracts on the retinal diseases such as AMD either for treatment or prevention of disease. Materials and methods: Fifteen studies were included in this literature review and assessed possible herbal treatments or preventions of AMD or its related diseases and risk factors. Results: From a wide range of medicinal plants, Artemisia annua contained artemisinin, Lycium barbarum, Fructus barbarum rich in carotenoids like zeaxanthin, Scutellaria baicalensis contained wogonin, saffron, rosemary contained carnosic acid, and Melissa officinalis are of the most important and beneficial medicinal plants that can be used for production and design of new drugs and therapeutics for AMD. They act via different mechanisms such as anti-oxidation, anti-VEGF, or anti-inflammatory actions. There are several other important herbal effective compounds for AMD, such as fisetin and luteolin that are polyphenols. Also, there are other herbal compounds such as HESA-A, Traditional Chinese Medicine (TCM), Guibi-tang (GBT), Samul-tang (SMT), and Sipjeondaebo-tang (SDT) that are contained in several different beneficial medicinal plants and their extracts for AMD. Conclusion: There is a need for more investigations on these medicinal plants and their benefits on AMD, but they can be beneficial in lowering the risk of AMD or several other retinal diseases and prevention of them. For each mechanism included in AMD pathogenesis, one or more medicinal plant is introduced in this review.

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An economical and highly adaptable optogenetics system for individual and population-level manipulation of Caenorhabditis elegans

BMC Biology ◽

10.1186/s12915-021-01085-2 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

M. Koopman ◽

L. Janssen ◽

E. A. A. Nollen

Keyword(s):

Caenorhabditis Elegans ◽

Light Stimulus ◽

Cholinergic Neurons ◽

Model Organisms ◽

Parameter Study ◽

Multiple Model ◽

Excitable Cells ◽

Specific Expression ◽

C Elegans ◽

Age Related

Abstract Background Optogenetics allows the experimental manipulation of excitable cells by a light stimulus without the need for technically challenging and invasive procedures. The high degree of spatial, temporal, and intensity control that can be achieved with a light stimulus, combined with cell type-specific expression of light-sensitive ion channels, enables highly specific and precise stimulation of excitable cells. Optogenetic tools have therefore revolutionized the study of neuronal circuits in a number of models, including Caenorhabditis elegans. Despite the existence of several optogenetic systems that allow spatial and temporal photoactivation of light-sensitive actuators in C. elegans, their high costs and low flexibility have limited wide access to optogenetics. Here, we developed an inexpensive, easy-to-build, modular, and adjustable optogenetics device for use on different microscopes and worm trackers, which we called the OptoArm. Results The OptoArm allows for single- and multiple-worm illumination and is adaptable in terms of light intensity, lighting profiles, and light color. We demonstrate OptoArm’s power in a population-based multi-parameter study on the contributions of motor circuit cells to age-related motility decline. We found that individual components of the neuromuscular system display different rates of age-dependent deterioration. The functional decline of cholinergic neurons mirrors motor decline, while GABAergic neurons and muscle cells are relatively age-resilient, suggesting that rate-limiting cells exist and determine neuronal circuit ageing. Conclusion We have assembled an economical, reliable, and highly adaptable optogenetics system which can be deployed to address diverse biological questions. We provide a detailed description of the construction as well as technical and biological validation of our set-up. Importantly, use of the OptoArm is not limited to C. elegans and may benefit studies in multiple model organisms, making optogenetics more accessible to the broader research community.

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Medicinal plants and natural products as neuroprotective agents in age-related macular degeneration

Neural Regeneration Research ◽

10.4103/1673-5374.284978 ◽

2020 ◽

Vol 15 (12) ◽

pp. 2207

Author(s):

Isabel Martínez-Solís ◽

Francisco Bosch-Morell ◽

Victoria Villagrasa ◽

Teresa Ortega ◽

Nuria Acero ◽

...

Keyword(s):

Natural Products ◽

Medicinal Plants ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Neuroprotective Agents ◽

Age Related

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A proteomics database for CNS proteins of the great pond snail Lymnaea stagnalis

10.1101/2021.05.03.442491 ◽

2021 ◽

Author(s):

Sarah Wooller ◽

Aikaterini Anagnostopoulou ◽

Benno Kuropka ◽

Michael Crossley ◽

Paul R. Benjamin ◽

...

Keyword(s):

Molecular Mechanisms ◽

Lymnaea Stagnalis ◽

Model Organism ◽

Research Area ◽

Biological Data ◽

Model Organisms ◽

Pond Snail ◽

Data Sets ◽

Area Of Interest ◽

Age Related

Applications of key technologies in bioscientific and biomedical research, such as qRT-PCR or LC-MS based proteomics, are generating large biological data sets (omics data) which are useful for the identification and quantification of biomarkers involved in molecular mechanisms of any research area of interest. Genome, transcriptome and proteome databases are already available for a number of model organisms including vertebrates and invertebrates. However, there is insufficient information available for protein sequences of certain invertebrates, such as the great pond snail Lymnaea stagnalis, a model organism that has been used highly successfully in elucidating evolutionarily conserved mechanisms of learning and memory, ageing and age-related as well as amyloid beta induced memory decline. Here, we present the design and benchmarking of a new proteomics database (LymSt-PDB) for the identification of proteins from the Central Nervous System (CNS) of Lymnaea stagnalis by LC-MS based proteomics.

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Finding Ponce de Leon’s Pill: Challenges in Screening for Anti-Aging Molecules

F1000Research ◽

10.12688/f1000research.7821.1 ◽

2016 ◽

Vol 5 ◽

pp. 406 ◽

Cited By ~ 16

Author(s):

Surinder Kumar ◽

David B. Lombard

Keyword(s):

Model Organisms ◽

Cancer Type ◽

Pharmacological Interventions ◽

Aging Research ◽

Genetic Manipulations ◽

Age Related ◽

Probability Of Death ◽

Invertebrate Models ◽

Progressive Accumulation

Aging is characterized by the progressive accumulation of degenerative changes, culminating in impaired function and increased probability of death. It is the major risk factor for many human pathologies – including cancer, type 2 diabetes, and cardiovascular and neurodegenerative diseases – and consequently exerts an enormous social and economic toll. The major goal of aging research is to develop interventions that can delay the onset of multiple age-related diseases and prolong healthy lifespan (healthspan). The observation that enhanced longevity and health can be achieved in model organisms by dietary restriction or simple genetic manipulations has prompted the hunt for chemical compounds that can increase lifespan. Most of the pathways that modulate the rate of aging in mammals have homologs in yeast, flies, and worms, suggesting that initial screening to identify such pharmacological interventions may be possible using invertebrate models. In recent years, several compounds have been identified that can extend lifespan in invertebrates, and even in rodents. Here, we summarize the strategies employed, and the progress made, in identifying compounds capable of extending lifespan in organisms ranging from invertebrates to mice and discuss the formidable challenges in translating this work to human therapies.

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Sirtuins and Neuropeptide y downregulation in Flinders Sensitive Line Rat Model of Depression

Acta Neuropsychiatrica ◽

10.1017/neu.2021.36 ◽

2021 ◽

pp. 1-19

Author(s):

Miranda Stiernborg ◽

Paschalis Efstathopoulos ◽

Andreas Lennartsson ◽

Catharina Lavebratt ◽

Aleksander A. Mathé

Keyword(s):

Rat Model ◽

Histone Deacetylases ◽

Sirtuin 1 ◽

Model Organisms ◽

Age Related ◽

Age Dependent ◽

Sensitive Line ◽

And Control ◽

Temporal Trajectory ◽

Flinders Sensitive Line

Abstract Objective: Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3 month old and 14-15 month old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like-ageing interaction. Methods: Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. Results: PFC. Sirt1 expression was decreased in FSL (p=0.001). An interaction between age and genotype was found (p=0.032); young FSL had lower Sirt1 with respect to both age (p=0.026) and genotype (p=0.001). Sirt2 was lower in FSL (p=0.003). Npy mRNA was downregulated in FSL (p=0.001) but did not differ between the young and old rat groups. Hippocampus.Sirt1 was reduced in young FSL compared to young FRL (p=0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p=0.003). Effects of ageing could not be investigated due to loss of samples. Conclusions: i. This is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression ; ii. The changes are age dependent; iii. Sirtuins are potential targets for treatment of age-related neurodegenerative diseases.

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