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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Terpenoids as Emerging Senotherapeutics: Mechanistic Insights and Therapeutic Potential
Sungwoo Yi1, Jung Yoon Park1, Sung-Joon Lee1,2,3
1Department of Biotechnology, Graduate School of Biotechnology, Korea University, Seoul 02841, Republic of Korea.
Abstract:
Cellular senescence, characterized by stable cell cycle arrest, drives organismal aging and functional decline. Senescent cells (SnCs) increase in multiple tissues with age and contribute to pathology by resisting apoptosis, impairing regeneration, and releasing senescence-associated secretory phenotype (SASP) factors. Senotherapeutics, including senolytics and senomorphics, aim to reduce the impact of SnCs by selectively clearing SnCs or suppressing SASP production. Natural terpenoids are structurally diverse plant- and fungus-derived metabolites with antioxidant, anti-inflammatory, and cytoprotective properties. Growing evidence supports their ability to counteract senescence-associated phenotypes, including senescence-associated β-galactosidase (SA-β-gal) activity and the expression of p53, p21, and p16. In this review, we examine mono-, sesqui-, di-, and triterpenoids that modulate cell cycle regulation, SASP attenuation, redox homeostasis, mitochondrial function, autophagy, and apoptosis-related mechanisms. We also outline the principal pathways underlying these anti-senescence activities and highlight natural terpenoids as emerging modulators of cellular senescence.
Insights
Natural terpenoids show promise in combating cellular senescence, a key driver of aging. These compounds may offer new senotherapeutic strategies by targeting aging hallmarks and reducing harmful senescence-associated secretory phenotypes.
Area of Science:
- Gerontology and cellular biology
- Natural product chemistry
Background:
- Cellular senescence drives aging and age-related diseases by accumulating senescent cells (SnCs) that resist apoptosis and release harmful factors.
- Senotherapeutics aim to clear SnCs or suppress their detrimental senescence-associated secretory phenotype (SASP).
Purpose of the Study:
- To review natural terpenoids as potential senotherapeutics.
- To explore their mechanisms in modulating senescence-associated phenotypes.
Main Methods:
- Literature review of mono-, sesqui-, di-, and triterpenoids.
- Analysis of their effects on cell cycle regulation, SASP, redox balance, mitochondrial function, autophagy, and apoptosis.
Main Results:
- Natural terpenoids counteract senescence markers like SA-β-gal, p53, p21, and p16.
- They modulate key pathways including cell cycle arrest, SASP, redox homeostasis, and apoptosis.
Conclusions:
- Natural terpenoids exhibit significant potential as senotherapeutics.
- They offer a promising avenue for developing novel anti-aging interventions by targeting cellular senescence mechanisms.
