Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells

Area of Science:

• Gerontology
• Cell Biology
• Phytochemistry

Background:

• Aging is linked to increased oxidative stress (OS) and antioxidant imbalance, raising the risk of chronic and neurodegenerative diseases.
• Premature senescence in cells can be induced by agents like hydrogen peroxide (H₂O₂), mimicking aging-related cellular damage.
• Certain plants possess phytochemicals with potential antioxidant and antiaging properties, often recognized through traditional ethnobotanical uses.

Purpose of the Study:

• To investigate the antisenescence effects of four plant species (Falcaria vulgaris, Ixiolirion tataricum, Ajuga chamaecistus, and Scabiosa flavida) on H₂O₂-induced premature senescence in NIH3T3 fibroblasts.
• To evaluate the impact of these plant extracts on oxidative stress markers, cell viability, cell cycle progression, and senescence-associated gene expression.
• To identify specific plant species with significant antiaging potential and understand their underlying mechanisms.

Main Methods:

• Cell viability was assessed using the MTT assay.
• Oxidative stress markers, including lipid peroxidation (LPO) and reactive oxygen species (ROS), and senescence-associated ß-galactosidase (SA-ß-GAL) activity were quantified.
• Cell cycle distribution was analyzed via flow cytometry.
• The expression of senescence-related genes (p38, p53, p16) and inflammatory mediators was determined using real-time RT-PCR.

Main Results:

• H₂O₂ treatment significantly reduced cell viability and increased ROS and LPO levels, alongside elevated SA-ß-GAL activity.
• Scabiosa flavida demonstrated the most potent antisenescence effects, exhibiting low cytotoxicity, reduced OS markers, and decreased SA-ß-GAL activity.
• Falcaria vulgaris, Ixiolirion tataricum, and Ajuga chamaecistus also showed varying degrees of efficacy.
• S. flavida modulated the cell cycle by reducing G0/G1 arrest and promoting G2/M transition, and downregulated key aging-related genes (p38, p53, p16) and inflammatory cytokines.

Conclusions:

• Scabiosa flavida effectively inhibits H₂O₂-induced premature senescence in fibroblasts by mitigating oxidative stress and modulating key aging pathways.
• The plant's ability to reduce OS, SA-ß-GAL activity, and downregulate senescence markers makes it a promising candidate for antiaging research and development.
• Further investigation into the specific phytochemicals within S. flavida could lead to novel antiaging therapeutic strategies.