PROLONGATION OF HUMAN LIFESPAN BY IMMATURE PEAR EXTRACT MEDIATED SIRTUIN-RELATED GENE EXPRESSION

Abstract Demographics of the world are changing rapidly with older populations growing at an unprecedented rate. Cellular senescence, a decline of cellular function due to aging, causes gradual loss of physiological functions. Several cellular senescence-related chronic diseases, such as metabolic syndrome, cardiovascular disease, cancer, osteoporosis, diabetes, and hypertension, negatively affect the quality of human life. Intervention in the cellular senescence process may reduce these incidences and slow the progression of age-related diseases, while contributing to the longevity of healthy human lifespans. Saccharomyces cerevisiae, the budding yeast, is a simple model system that can provide significant insights into the human genetics and molecular biology of senescence and is considered suitable as a cellular model for research on mammalian cells. The aim of our study was to investigate the anti-aging effects of immature pear fruit extract (IPE) on yeast cells and its possible application to extend healthy lifespan in humans. Anti-aging effects of IPE were investigated using a chronological lifespan assay on S. cerevisiae cells. The chronological lifespan of the yeast treated with IPE at 1% (v/v) was significantly extended than that of untreated cells (p < 0.05). The expression of sirtuin-related genes, which regulate cellular senescence, was examined by reverse transcription-polymerase chain reaction and found to be significantly increased following IPE treatment. These results suggest that sirtuin-related genes have important roles in IPE-regulated lifespan extension, which provides a mechanism by which IPE could affect mammalian cells and potentially extend healthy human lifespans.

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Anti-Aging Effects of Hydrophobic and Hydrophilic Components From Immature Pear Fruits Extract

Innovation in Aging ◽

10.1093/geroni/igaa057.427 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 130-130

Author(s):

Akira Ogita ◽

Wakae Murata ◽

Ken Yamauchi ◽

Akiko Sakai ◽

Yoshihiro Yamaguchi ◽

...

Keyword(s):

Cellular Senescence ◽

Mammalian Cells ◽

Human Life ◽

Yeast Cells ◽

Aging Effects ◽

Yeast Saccharomyces Cerevisiae ◽

Chronological Lifespan ◽

Human Lifespan ◽

Age Related ◽

Useful Components

Abstract Cellular senescence, the decline of cellular function due to aging, causes gradual loss of physiological functions and induces some chronic diseases, which negatively affect the quality of human life. Intervention in the cellular senescence process may reduce these incidences and delay the progression of age-related diseases, thereby contributing to the longevity of human lifespan. The budding yeast, Saccharomyces cerevisiae, is a model system that can provide significant insights into the genetics and molecular biology of senescence and is a suitable cellular model for research on mammalian cells. In the 2019 GSA meeting, we had revealed that the prolongation of yeast cell lifespan was induced by the addition of immature pear fruits extracts (iPE). In this study, we have focused on investigating the anti-senescence effects of hydrophilic (WiPE) and hydrophobic (OiPE) components of iPE on yeast cells and their genes and their possible application in extending human lifespan. The anti-aging effects of iPE were investigated using a chronological lifespan assay on S. cerevisiae cells. The chronological lifespan of the yeast was significantly extended in those treated with both WiPE and OiPE at 1% (v/v). The expression of sirtuin-related genes, which regulate cellular senescence, was examined by RT-PCR. Interestingly, gene expression was found to be significantly increased only in WiPE treated cells. The results suggested that the different polarity components from iPE exhibited anti-aging effects on the cells via different mechanisms. Research on the identification of useful components in iPE and the possibility of application to mammalian cells is ongoing.

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Immature Pear Extract Constituents Exert Multifaceted Anti-aging Effects

Innovation in Aging ◽

10.1093/geroni/igab046.2551 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 684-684

Author(s):

Akira Ogita ◽

Wakae Murata ◽

Ken Yamauchi ◽

Akiko Sakai ◽

Yoshihiro Yamaguchi ◽

...

Keyword(s):

Gene Expression ◽

Cellular Senescence ◽

Mammalian Cells ◽

Human Life ◽

The Body ◽

Yeast Cells ◽

Related Gene ◽

Aging Effects ◽

Chronological Lifespan ◽

Age Related

Abstract Cellular senescence causes a gradual loss of physiological functions and induces chronic diseases, which negatively affect the quality of human life. Intervention in the cellular senescence process may reduce the incidence of these diseases while delaying the progression of age-related diseases, thereby prolonging human lifespan. In our previous study, we found that extending the chronological lifespan of budding yeast cells, a suitable cellular model for research on mammalian cells, could be achieved by adding immature pear extract (iPE). Moreover, at the 2020 GSA meeting, using a colony-counting method, we reported that both hydrophilic (WiPE) and hydrophobic (OiPE) iPE components exhibited a chronological lifespan prolongation on yeast cells. In this study, the expression of sirtuin-related genes, which regulate cellular senescence, was verified by quantitative real-time reverse-transcription polymerase chain reaction. Interestingly, sirtuin-related gene expression was significantly increased in the WiPE-treated cells only, and OiPE could extend the chronological lifespan of yeast cells through the mechanisms not involved in sirtuin-related gene expression. In general, hydrophobic and hydrophilic components exhibit different degradation and metabolism in cells. Since each component has a different strategy of absorption and excretion in the body, we hypothesize that iPE with multiple active components will have multifaceted effects on anti-aging. Our research on elucidating the mechanism of lifespan extension by OiPE and its application to mammalian cells is ongoing.

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Resveratrol: A Sirtuin Activator and The Fountain of Youth

The Indonesian Biomedical Journal ◽

10.18585/inabj.v7i1.16 ◽

2015 ◽

Vol 7 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Anna Meiliana ◽

Nurrani Mustika Dewi ◽

Andi Wijaya

Keyword(s):

Caloric Restriction ◽

Healthy Aging ◽

Myocardial Infarct ◽

Functional Decline ◽

Steady Increase ◽

Healthy Human ◽

Aging Research ◽

Human Lifespan ◽

Age Related ◽

Fountain Of Youth

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator

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Apigenin Alleviates Oxidative Stress-Induced Cellular Senescence via Modulation of the SIRT1-NAD+-CD38 Axis

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500592 ◽

2021 ◽

pp. 1-16

Author(s):

Bing Si Li ◽

Ri Zhe Zhu ◽

Seok-Hee Lim ◽

Jae Ho Seo ◽

Byung-Min Choi

Keyword(s):

Oxidative Stress ◽

Cellular Senescence ◽

Lung Diseases ◽

Molecular Mechanisms ◽

Driving Mechanism ◽

Dependent Manner ◽

Aging Effects ◽

Chronic Lung Diseases ◽

Age Related ◽

The Impact

Oxidative stress-induced cellular senescence is now regarded as an important driving mechanism in chronic lung diseases-particularly chronic obstructive pulmonary disease (COPD). 4′,5,7-trihydroxyflavone (Apigenin) is a natural flavonoid product abundantly present in fruits, vegetables, and Chinese medicinal herbs. It has been known that apigenin has anti-oxidant, anti-inflammatory and liver-protecting effects. The efficacy of apigenin for lung aging, however, has not been reported. In this study, we selected the hydrogen peroxide (H2O[Formula: see text]- or doxorubicin (DOXO)-induced senescence model in WI-38 human embryonic lung fibroblast cells to determine the potential anti-aging effects of apigenin in vitro and associated molecular mechanisms. We found that apigenin reduced senescence-associated [Formula: see text]-galactosidase (SA-[Formula: see text]-gal) activity and promoted cell growth, concomitant with a decrease in levels of Acetyl (ac)-p53, p21[Formula: see text], and p16[Formula: see text] and an increase in phospho (p)-Rb. Apigenin also increased the activation ratio of silent information regulator 1 (SIRT1), nicotinamide adenine dinucleotide (NAD[Formula: see text], and NAD[Formula: see text]/NADH and inhibited cluster of differentiation 38 (CD38) activity in a concentration-dependent manner. SIRT1 inhibition by SIRT1 siRNA abolished the anti-aging effect of apigenin. In addition, CD38 inhibition by CD38 siRNA or apigenin increased the SIRT1 level and reduced H2O2-induced senescence. Our findings suggest that apigenin is a promising phytochemical for reducing the impact of senescent cells in age-related lung diseases such as COPD.

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THE LONGEVITY CONSORTIUM VISION

Innovation in Aging ◽

10.1093/geroni/igz038.758 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S208-S209

Author(s):

Daniel S Evans ◽

Steven R Cummings ◽

Nicholas Schork

Keyword(s):

Healthy Aging ◽

Human Longevity ◽

Cooperative Research ◽

Healthy Human ◽

Molecular Features ◽

Human Lifespan ◽

Age Related ◽

Show Evidence ◽

Funding Opportunities ◽

Multiple Chronic Diseases

Abstract Molecular factors and pathways promoting human longevity and healthy aging can potentially delay or prevent multiple chronic diseases and conditions, but identifying such factors that can be pharmacologically targeted requires an integrated multidisciplinary approach. We describe the design of the five research projects and three cores of the Longevity Consortium (LC) and how their cooperative research is designed to discover molecular factors and pathways that can predict healthy human aging and longevity, associate with extreme human lifespan, show relevance to chronic age-related conditions, respond to interventions to slow aging in mice, and show evidence for association with lifespan across species. A systems biology approach is undertaken to identify common molecular features across human traits and organisms, and a chemoinformatics approach to link molecular targets to candidate healthy aging interventions. The LC results are made publicly available and we provide funding opportunities to the scientific community to support pilot projects.

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Exercise tames the wild side of the Myc network: a hypothesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00027.2012 ◽

2012 ◽

Vol 303 (1) ◽

pp. E18-E30 ◽

Cited By ~ 14

Author(s):

Kishorchandra Gohil ◽

George A. Brooks

Keyword(s):

Stem Cell ◽

Primary Source ◽

Physical Activities ◽

Healthy Human ◽

Human Lifespan ◽

Age Related ◽

Mitochondrial Functions ◽

Cardiovascular Pathologies ◽

Exercise Induced ◽

Cell Growth And Proliferation

We propose that the well-documented therapeutic actions of repeated physical activities over human lifespan are mediated by the rapidly turning over proto-oncogenic Myc (myelocytomatosis) network of transcription factors. This transcription factor network is unique in utilizing promoter and epigenomic (acetylation/deacetylation, methylation/demethylation) mechanisms for controlling genes that include those encoding intermediary metabolism (the primary source of acetyl groups), mitochondrial functions and biogenesis, and coupling their expression with regulation of cell growth and proliferation. We further propose that remote functioning of the network occurs because there are two arms of this network, which consists of driver cells (e.g., working myocytes) that metabolize carbohydrates, fats, proteins, and oxygen and produce redox-modulating metabolites such as H2O2, NAD+, and lactate. The exercise-induced products represent autocrine, paracrine, or endocrine signals for target recipient cells (e.g., aortic endothelium, hepatocytes, and pancreatic β-cells) in which the metabolic signals are coupled with genomic networks and interorgan signaling is activated. And finally, we propose that lactate, the major metabolite released from working muscles and transported into recipient cells, links the two arms of the signaling pathway. Recently discovered contributions of the Myc network in stem cell development and maintenance further suggest that regular physical activity may prevent age-related diseases such as cardiovascular pathologies, cancers, diabetes, and neurological functions through prevention of stem cell dysfunctions and depletion with aging. Hence, regular physical activities may attenuate the various deleterious effects of the Myc network on health, the wild side of the Myc-network, through modulating transcription of genes associated with glucose and energy metabolism and maintain a healthy human status.

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Advancements in therapeutic drugs targeting of senescence

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622320964125 ◽

2020 ◽

Vol 11 ◽

pp. 204062232096412

Author(s):

Mingsheng Zhu ◽

Ping Meng ◽

Xian Ling ◽

Lili Zhou

Keyword(s):

Cellular Senescence ◽

Healthy Aging ◽

Early Stage ◽

Natural Aging ◽

Aging Effects ◽

Therapeutic Drugs ◽

Stage Of Development ◽

Age Related ◽

Therapeutic Value ◽

Nutrient Signaling

Aging leads to a high burden on society, both medically and economically. Cellular senescence plays an essential role in the initiation of aging and age-related diseases. Recent studies have highlighted the therapeutic value of senescent cell deletion in natural aging and many age-related disorders. However, the therapeutic strategies for manipulating cellular senescence are still at an early stage of development. Among these strategies, therapeutic drugs that target cellular senescence are arguably the most highly anticipated. Many recent studies have demonstrated that a variety of drugs exhibit healthy aging effects. In this review, we summarize different types of drugs promoting healthy aging – such as senolytics, senescence-associated secretory phenotype (SASP) inhibitors, and nutrient signaling regulators – and provide an update on their potential therapeutic merits. Taken together, our review synthesizes recent advancements in the therapeutic potentialities of drugs promoting healthy aging with regard to their clinical implications.

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Cellular Senescence in Lung Fibrosis

International Journal of Molecular Sciences ◽

10.3390/ijms22137012 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7012

Author(s):

Fernanda Hernandez-Gonzalez ◽

Rosa Faner ◽

Mauricio Rojas ◽

Alvar Agustí ◽

Manuel Serrano ◽

...

Keyword(s):

Cell Fate ◽

Cellular Senescence ◽

Lung Fibrosis ◽

Lung Diseases ◽

Physiological Mechanism ◽

Lung Parenchyma ◽

Scar Tissue ◽

Interstitial Lung Diseases ◽

Cellular Damage ◽

Age Related

Fibrosing interstitial lung diseases (ILDs) are chronic and ultimately fatal age-related lung diseases characterized by the progressive and irreversible accumulation of scar tissue in the lung parenchyma. Over the past years, significant progress has been made in our incomplete understanding of the pathobiology underlying fibrosing ILDs, in particular in relation to diverse age-related processes and cell perturbations that seem to lead to maladaptation to stress and susceptibility to lung fibrosis. Growing evidence suggests that a specific biological phenomenon known as cellular senescence plays an important role in the initiation and progression of pulmonary fibrosis. Cellular senescence is defined as a cell fate decision caused by the accumulation of unrepairable cellular damage and is characterized by an abundant pro-inflammatory and pro-fibrotic secretome. The senescence response has been widely recognized as a beneficial physiological mechanism during development and in tumour suppression. However, recent evidence strengthens the idea that it also drives degenerative processes such as lung fibrosis, most likely by promoting molecular and cellular changes in chronic fibrosing processes. Here, we review how cellular senescence may contribute to lung fibrosis pathobiology, and we highlight current and emerging therapeutic approaches to treat fibrosing ILDs by targeting cellular senescence.

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Cellular Senescence and Mammalian Healthspan

Innovation in Aging ◽

10.1093/geroni/igaa057.2655 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 742-742

Author(s):

Judith Campisi

Keyword(s):

Growth Factors ◽

Cell Fate ◽

Cellular Senescence ◽

Complex Cell ◽

Transgenic Mouse Models ◽

Bioactive Lipids ◽

Age Related ◽

Mammalian Tissues ◽

Secretory Phenotype ◽

Near Future

Abstract Cellular senescence is a complex cell fate, often induced by stress or damage, that can be beneficial or deleterious, depending on the physiological context and age of the organism. A prominent feature of senescent cells is a multi-faceted senescence-associated secretory phenotype (SASP), which includes growth factors, cytokine and chemokines, growth factors, proteases, bioactive lipids and metabolites. Senescent cells increase with age in most, if not all, mammalian tissues. Through the use of transgenic mouse models, senescent cells are now known to causally drive numerous age-related pathologies, largely through the SASP. Eliminating senescent cells, genetically or through the use of senolytic/senomorphic agents, can improve the health span, at least in mice, and hold promise for extension to humans in the near future.

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Dendranthema zawadskii var. lucidum (Nakai) J.H. Park Extract Inhibits Cellular Senescence in Human Dermal Fibroblasts and Aging-Related Inflammation in Rats

Processes ◽

10.3390/pr9050801 ◽

2021 ◽

Vol 9 (5) ◽

pp. 801

Author(s):

Jehun Choi ◽

Gwi-Yeong Jang ◽

Jeonghoon Lee ◽

Hae-Young Chung ◽

Hyung-Jun Noh ◽

...

Keyword(s):

Cellular Senescence ◽

Cell Cycle Progression ◽

Inflammatory Responses ◽

Dermal Fibroblast ◽

Dermal Fibroblasts ◽

Dependent Manner ◽

Aged Rats ◽

Age Related ◽

Dendranthema Zawadskii ◽

Beta Galactosidase

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.

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