• Title, Summary, Keyword: Senolytics

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Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases

  • Kang, Chanhee
    • Molecules and Cells
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    • v.42 no.12
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    • pp.821-827
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    • 2019
  • Aging is the most important single risk factor for many chronic diseases such as cancer, metabolic syndrome, and neurodegenerative disorders. Targeting aging itself might, therefore, be a better strategy than targeting each chronic disease individually for enhancing human health. Although much should be achieved for completely understanding the biological basis of aging, cellular senescence is now believed to mainly contribute to organismal aging via two independent, yet not mutually exclusive mechanisms: on the one hand, senescence of stem cells leads to exhaustion of stem cells and thus decreases tissue regeneration. On the other hand, senescent cells secrete many proinflammatory cytokines, chemokines, growth factors, and proteases, collectively termed as the senescence-associated secretory phenotype (SASP), which causes chronic inflammation and tissue dysfunction. Much effort has been recently made to therapeutically target detrimental effects of cellular senescence including selectively eliminating senescent cells (senolytics) and modulating a proinflammatory senescent secretome (senostatics). Here, we discuss current progress and limitations in understanding molecular mechanisms of senolytics and senostatics and therapeutic strategies for applying them. Furthermore, we propose how these novel interventions for aging treatment could be improved, based on lessons learned from cancer treatment.

Recent Trends on Telomerase Activators, Sirtuin Activators, and Senolytics as a Potential Anti-aging Agent (잠재적인 항노화제로 텔로머레이즈 활성화제, 서르튜언 활성화제, 세노릭틱스에 대한 최신 동향)

  • Kim, Moon-Moo
    • Journal of Life Science
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    • v.30 no.9
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    • pp.819-825
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    • 2020
  • All living organisms exhibit the characteristics of aging, such as skin wrinkle formation, muscle degeneration, cataracts, and hair graying as the number of aged cells increases over time. Senescence, which is known as a key cause of aging, is directly related to the aging of living organisms because cells are aged by external and internal factors and eventually cell proliferation is stopped. Senescence is caused by the gradual shortening of the telomere with cell division, and lifespan is determined by the length of the telomere. Recently, it has been found that the histone deacetylase, which can influence gene expression, is not only involved in yeast but also deeply involved in anti-aging mechanisms in both C. elegans and humans. It was also discovered that old cells play a decisive role in the aging phenomenon, and it has been reported that it is possible to promote the proliferation of young cells and delay aging by removing these senescent cells from the inside. Therefore, in order to develop potential anti-aging agents in the future, research should begin with an in-depth study of telomerase activators, sirtuin activators, and senolytics.

Senotherapeutics: emerging strategy for healthy aging and age-related disease

  • Kim, Eok-Cheon;Kim, Jae-Ryong
    • BMB Reports
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    • v.52 no.1
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    • pp.47-55
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    • 2019
  • Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. This review will present the current status of the development of senotherapeutics, in relation to aging itself and ARDs. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and ARDs.

Roles of Fisetin on Skin Barrier Function and Anti-aging in Epidermal Keratinocyte (각질형성세포에서 Fisetin의 피부장벽 기능 개선 및 항노화 효능 검증)

  • Lee, Kyung-Ha;Kim, Wanil
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.4
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    • pp.391-401
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    • 2020
  • Flavonoids are polyphenolic compounds derived from plants metabolites and are known to be capable of controlling various human physiological functions. Among them, fisetin (3,3', 3', 7-tetrahydroxyflavone) is found in various fruits and vegetables, and it has been recently known to restore the function of certain tissues through senolytic activity. In this study, targeting human epidermal keratinocytes, control of skin barrier genes and antioxidant efficacy of fisetin were analyzed. Fisetin increased the activity of telomerase and decreased the expression of CDKN1B. In addition, it increased the expression of KRT1, FLG, IVL, and DSP, which are main genes that make up the skin barrier. The fisetin also increased the expression of CerS3 and CerS4 genes, which are forms of ceramide synthases. These results show that the efficacy of fisetin is not limited as senolytics but is also involved in various physiological regulation of human keratinocytes. Therefore, we consider that fisetin could be used as an active ingredient in cosmetics and pharmaceuticals.

Can we rejuvenate? Implications of biological aging research (우리는 다시 젊어질 수 있는가? 생물학적 노화 연구의 시사점)

  • Son, Youlim;Kim, Jae-Ryong
    • Yeungnam University Journal of Medicine
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    • v.34 no.1
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    • pp.1-10
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    • 2017
  • The life history of man is summarized as a birth-aging-disease-death. Man eventually ages and dies. How long can humans live? What is aging? Why do we age? Is aging inevitable? Can we rejuvenate? Recent researches on biological aging suggest that humans might overcome aging and rejuvenate. In this paper, we review the biologic characteristics of aging and the latest results of biological aging research, implicating that aging can be controlled, further treated, and that humans can ultimately be rejuvenated.