scholarly journals Quest for Bioactive Compounds in Our Diet with Anti-Ageing and Anti-Aggregation Properties

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 34
Author(s):  
Nikoletta Papaevgeniou ◽  
Eleni Panagiotidou ◽  
Konstantina Filippopoulou ◽  
Niki Chondrogianni
Keyword(s):  
Bioactive Compounds ◽  
Replicative Senescence ◽  
Nematode Caenorhabditis Elegans ◽  
Age Related ◽  
Complex Process ◽  
Primary Fibroblasts ◽  
Gradual Failure ◽  
Bioactive Phytochemicals ◽  
Nrf2 Transcription Factor ◽  
Genetic And Environmental Factors

Ageing is a complex process affected by both genetic and environmental factors, characterized by a gradual failure of functionality, reduced stress response and resistance, leading to enhanced probability for age-related diseases and mortality. During the last decades, natural compounds have attracted the attention of researchers in the quest of bioactive phytochemicals with anti-ageing properties. For a few of these compounds an extra advantage appears; many of them have been shown to decelerate the progression of age-related diseases with emphasis on aggregation-related diseases. Using the nematode Caenorhabditis elegans along with the replicative senescence model of human primary fibroblasts, we have identified compounds that are part of our diet with anti-oxidation, anti-ageing and anti-aggregation activities. Some of the identified compounds promote their anti-ageing activity through activation of the proteasome, others through the activation of Nrf2 transcription factor, while others through inhibition of glucose transporters (GLUTs). Our work identifies new bioactive compounds with anti-ageing and/or anti-aggregation properties or reveals additional beneficial properties on already known bioactive compounds.

scholarly journals Increased CD47 and MHC Class I Inhibitory Signals Expression in Senescent CD1 Primary Mouse Lung Fibroblasts

2021 ◽  
Vol 22 (19) ◽  
pp. 10215
Author(s):  
Elisa Hernández-Mercado ◽  
Jessica Lakshmi Prieto-Chávez ◽  
Lourdes Andrea Arriaga-Pizano ◽  
Salomon Hernández-Gutierrez ◽  
Fela Mendlovic ◽  
...  
Keyword(s):  
Immune System ◽  
Replicative Senescence ◽  
Class I ◽  
Lung Fibroblasts ◽  
Mouse Lung ◽  
Class I Mhc ◽  
Mhc I ◽  
Age Related ◽  
Primary Mouse ◽  
Primary Fibroblasts

Cellular senescence is more than a proliferative arrest in response to various stimuli. Senescent cells (SC) participate in several physiological processes, and their adequate removal is essential to maintain tissue and organism homeostasis. However, SC accumulation in aging and age-related diseases alters the tissue microenvironment leading to deterioration. The immune system clears the SC, but the specific scenarios and mechanisms related to recognizing and eliminating them are unknown. Hence, we aimed to evaluate the existence of three regulatory signals of phagocytic function, CD47, major histocompatibility complex class I (MHC-I), and calreticulin, present in the membrane of SC. Therefore, primary fibroblasts were isolated from CD1 female mice lungs, and stress-induced premature senescence (SIPS) was induced with hydrogen peroxide. Replicative senescence (RS) was used as a second senescent model. Our results revealed a considerable increment of CD47 and MHC-I in RS and SIPS fibroblasts. At the same time, no significant changes were found in calreticulin, suggesting that those signals might be associated with evading immune system recognition and thus averting senescent cells clearance.

A Developmental Perspective on the Genetic Basis of Alcohol Use Disorder

2018 ◽  
Author(s):  
Elisa M. Trucco ◽  
Gabriel L. Schlomer ◽  
Brian M. Hicks
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Developmental Perspective ◽  
Relative Contribution ◽  
Intermediate Phenotypes ◽  
Problematic Alcohol ◽  
Age Related ◽  
Genetic And Environmental Factors ◽  
Problematic Alcohol Use

Approximately 48–66% of the variation in alcohol use disorders is heritable. This chapter provides an overview of the genetic influences that contribute to alcohol use disorder within a developmental perspective. Namely, risk for problematic alcohol use is framed as a function of age-related changes in the relative contribution of genetic and environmental factors and an end state of developmental processes. This chapter discusses the role of development in the association between genes and the environment on risk for alcohol use disorder. Designs used to identify genetic factors relevant to problematic alcohol use are discussed. Studies examining developmental pathways to alcohol use disorder with a focus on endophenotypes and intermediate phenotypes are reviewed. Finally, areas for further investigation are offered.

scholarly journals Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Ting Zhao ◽  
Shengfan Ye ◽  
Zimu Tang ◽  
Liwei Guo ◽  
Zhipeng Ma ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Brain Aging ◽  
Ventricular Zone ◽  
Human Fibroblasts ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Antioxidant Genes ◽  
Age Related

AbstractReactive oxygen species (ROS) stress has been demonstrated as potentially critical for induction and maintenance of cellular senescence, and been considered as a contributing factor in aging and in various neurological disorders including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In response to low-level ROS stress, the expression of Δ133p53, a human p53 isoform, is upregulated to promote cell survival and protect cells from senescence by enhancing the expression of antioxidant genes. In normal conditions, the basal expression of Δ133p53 prevents human fibroblasts, T lymphocytes, and astrocytes from replicative senescence. It has been also found that brain tissues from AD and ALS patients showed decreased Δ133p53 expression. However, it is uncharacterized if Δ133p53 plays a role in brain aging. Here, we report that zebrafish Δ113p53, an ortholog of human Δ133p53, mainly expressed in some of the radial glial cells along the telencephalon ventricular zone in a full-length p53-dependent manner. EDU-labeling and cell lineage tracing showed that Δ113p53-positive cells underwent cell proliferation to contribute to the neuron renewal process. Importantly, Δ113p53M/M mutant telencephalon possessed less proliferation cells and more senescent cells compared to wild-type (WT) zebrafish telencephalon since 9-months old, which was associated with decreased antioxidant genes expression and increased level of ROS in the mutant telencephalon. More interestingly, unlike the mutant fish at 5-months old with cognition ability, Δ113p53M/M zebrafish, but not WT zebrafish, lost their learning and memory ability at 19-months old. The results demonstrate that Δ113p53 protects the brain from aging by its antioxidant function. Our finding provides evidence at the organism level to show that depletion of Δ113p53/Δ133p53 may result in long-term ROS stress, and finally lead to age-related diseases, such as AD and ALS in humans.

scholarly journals Change by challenge: A common genetic basis behind childhood cognitive development and cognitive training

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bruno Sauce ◽  
John Wiedenhoeft ◽  
Nicholas Judd ◽  
Torkel Klingberg
Keyword(s):  
Cognitive Development ◽  
Brain Plasticity ◽  
Training Sample ◽  
Age Related ◽  
Central Piece ◽  
Gene Environment ◽  
Related Development ◽  
Explained Variation ◽  
Genetic And Environmental Factors ◽  
Cognitive Challenges

AbstractThe interplay of genetic and environmental factors behind cognitive development has preoccupied multiple fields of science and sparked heated debates over the decades. Here we tested the hypothesis that developmental genes rely heavily on cognitive challenges—as opposed to natural maturation. Starting with a polygenic score (cogPGS) that previously explained variation in cognitive performance in adults, we estimated its effect in 344 children and adolescents (mean age of 12 years old, ranging from 6 to 25) who showed changes in working memory (WM) in two distinct samples: (1) a developmental sample showing significant WM gains after 2 years of typical, age-related development, and (2) a training sample showing significant, experimentally-induced WM gains after 25 days of an intense WM training. We found that the same genetic factor, cogPGS, significantly explained the amount of WM gain in both samples. And there was no interaction of cogPGS with sample, suggesting that those genetic factors are neutral to whether the WM gains came from development or training. These results represent evidence that cognitive challenges are a central piece in the gene-environment interplay during cognitive development. We believe our study sheds new light on previous findings of interindividual differences in education (rich-get-richer and compensation effects), brain plasticity in children, and the heritability increase of intelligence across the lifespan.

scholarly journals Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4317
Author(s):  
Yan-Xi Chen ◽  
Phuong Thu Nguyen Le ◽  
Tsai-Teng Tzeng ◽  
Thu-Ha Tran ◽  
Anh Thuc Nguyen ◽  
...  
Keyword(s):  
Model Systems ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
Cancer Cell Growth ◽  
C Elegans ◽  
Age Related ◽  
Ampk Activity ◽  
Β Amyloid ◽  
Amp Activated Protein Kinase ◽  
U87 Cells

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer’s disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses β-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

GENETIC AND ENVIRONMENTAL FACTORS ASSOCIATED WITH RETICULAR PSEUDODRUSEN IN AGE-RELATED MACULAR DEGENERATION

Retina ◽  
2013 ◽  
Vol 33 (5) ◽  
pp. 998-1004 ◽  
Author(s):  
Nathalie Puche ◽  
Rocio Blanco-Garavito ◽  
Florence Richard ◽  
Nicolas Leveziel ◽  
Jennyfer Zerbib ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Factors Associated ◽  
Reticular Pseudodrusen ◽  
Age Related ◽  
Genetic And Environmental Factors

scholarly journals Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 332 ◽  
Author(s):  
Jennifer T. Zieba ◽  
Yi-Ting Chen ◽  
Brendan H. Lee ◽  
Yangjin Bae
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Human Genetics ◽  
Skeletal Development ◽  
Gene Activation ◽  
Fracture Repair ◽  
Loss Of Function ◽  
Age Related ◽  
Complex Process ◽  
And Cartilage

Skeletal development is a complex process which requires the tight regulation of gene activation and suppression in response to local signaling pathways. Among these pathways, Notch signaling is implicated in governing cell fate determination, proliferation, differentiation and apoptosis of skeletal cells-osteoblasts, osteoclasts, osteocytes and chondrocytes. Moreover, human genetic mutations in Notch components emphasize the critical roles of Notch signaling in skeletal development and homeostasis. In this review, we focus on the physiological roles of Notch signaling in skeletogenesis, postnatal bone and cartilage homeostasis and fracture repair. We also discuss the pathological gain- and loss-of-function of Notch signaling in bone and cartilage, resulting in osteosarcoma and age-related degenerative diseases, such as osteoporosis and osteoarthritis. Understanding the physiological and pathological function of Notch signaling in skeletal tissues using animal models and human genetics will provide new insights into disease pathogenesis and offer novel approaches for the treatment of bone/cartilage diseases.

scholarly journals The Role of Selected Bioactive Compounds in the Prevention of Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 229 ◽  
Author(s):  
Wojciech Grodzicki ◽  
Katarzyna Dziendzikowska
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Health Concern ◽  
Elderly Persons ◽  
Global Public Health ◽  
Age Related ◽  
In Vivo Animal Model

Neurodegeneration is a feature of many debilitating, incurable age-dependent diseases that affect the nervous system and represent a major threat to the health of elderly persons. Because of the ongoing process of aging experienced by modern societies, the increasing prevalence of neurodegenerative diseases is becoming a global public health concern. A major cause of age-related dementia is Alzheimer’s disease (AD). Currently, there are no effective therapies to slow, stop, or reverse the progression of this disease. However, many studies have suggested that modification of lifestyle factors, such as the introduction of an appropriate diet, can delay or prevent the onset of this disorder. Diet is currently considered to be a crucial factor in controlling health and protecting oneself against oxidative stress and chronic inflammation, and thus against chronic degenerative diseases. A large number of bioactive food compounds may influence the pathological mechanisms underlying AD. Among them, phenolic compounds, omega-3 fatty acids, fat-soluble vitamins, isothiocyanates, and carotenoids seem to be promising. They act not only as antioxidant and anti-inflammatory agents, but also as active modulators of the pathological molecular mechanisms that play a role in AD development, including the formation of amyloid plaques and tau tangles, the main hallmarks of AD pathology. In vivo animal model studies as well as clinical and epidemiological research suggest that nutritional intervention has a positive effect on the health of older people and may prevent age-related cognitive decline, especially when the diet contains more than one bioactive nutrient. The Mediterranean diet and in particular its combination with Dietary Approaches to Stop Hypertension, which is called the MIND diet, are nutritional patterns based on many products rich in bioactive compounds that appear to be the most effective in preventing neurodegeneration. The present review gathers evidence that supports the neuroprotective effect of bioactive substances.

scholarly journals The Epigenetic Link between Polyphenols, Aging and Age-Related Diseases

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1094
Author(s):  
Itika Arora ◽  
Manvi Sharma ◽  
Liou Y. Sun ◽  
Trygve O. Tollefsbol
Keyword(s):  
Disease Progression ◽  
Fruits And Vegetables ◽  
Strong Association ◽  
Therapeutic Interventions ◽  
Dietary Polyphenols ◽  
Age Related ◽  
Non Coding Rna ◽  
Risk Of Mortality ◽  
Complex Process ◽  
Increased Risk

Aging is a complex process mainly categorized by a decline in tissue, cells and organ function and an increased risk of mortality. Recent studies have provided evidence that suggests a strong association between epigenetic mechanisms throughout an organism’s lifespan and age-related disease progression. Epigenetics is considered an evolving field and regulates the genetic code at several levels. Among these are DNA changes, which include modifications to DNA methylation state, histone changes, which include modifications of methylation, acetylation, ubiquitination and phosphorylation of histones, and non-coding RNA changes. As a result, these epigenetic modifications are vital targets for potential therapeutic interventions against age-related deterioration and disease progression. Dietary polyphenols play a key role in modulating these modifications thereby delaying aging and extending longevity. In this review, we summarize recent advancements linking epigenetics, polyphenols and aging as well as critical findings related to the various dietary polyphenols in different fruits and vegetables. In addition, we cover studies that relate polyphenols and their epigenetic effects to various aging-related diseases such as cardiovascular diseases, neurodegenerative diseases, autoimmune disorders, diabetes, osteoporosis and cancer.

scholarly journals Gene therapy for hearing loss

2019 ◽  
Vol 28 (R1) ◽  
pp. R65-R79 ◽  
Author(s):  
Ryotaro Omichi ◽  
Seiji B Shibata ◽  
Cynthia C Morton ◽  
Richard J H Smith
Keyword(s):  
Gene Therapy ◽  
Hearing Loss ◽  
Inner Ear ◽  
Viral Vectors ◽  
Therapeutic Potential ◽  
Late Onset ◽  
Science Research ◽  
Gene Replacement ◽  
Age Related ◽  
Genetic And Environmental Factors

Abstract Sensorineural hearing loss (SNHL) is the most common sensory disorder. Its underlying etiologies include a broad spectrum of genetic and environmental factors that can lead to hearing loss that is congenital or late onset, stable or progressive, drug related, noise induced, age related, traumatic or post-infectious. Habilitation options typically focus on amplification using wearable or implantable devices; however exciting new gene-therapy-based strategies to restore and prevent SNHL are actively under investigation. Recent proof-of-principle studies demonstrate the potential therapeutic potential of molecular agents delivered to the inner ear to ameliorate different types of SNHL. Correcting or preventing underlying genetic forms of hearing loss is poised to become a reality. Herein, we review molecular therapies for hearing loss such as gene replacement, antisense oligonucleotides, RNA interference and CRISPR-based gene editing. We discuss delivery methods, techniques and viral vectors employed for inner ear gene therapy and the advancements in this field that are paving the way for basic science research discoveries to transition to clinical trials.

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