Chemical screen identifies a geroprotective role of quercetin in premature aging

Area of Science:

• Gerontology
• Cell Biology
• Natural Product Chemistry

Background:

• Aging is a primary risk factor for numerous diseases.
• Aging research aims to develop therapies that slow aging and mitigate associated illnesses.
• Developing effective anti-aging interventions is a significant medical challenge.

Purpose of the Study:

• To identify geroprotective compounds from a natural product library.
• To evaluate the efficacy of candidate compounds in premature aging models.
• To elucidate the mechanisms underlying the anti-aging effects of promising compounds.

Main Methods:

• Screening of a natural product library using Werner syndrome (WS) human mesenchymal stem cells (hMSCs) as a premature aging model.
• Detailed investigation of quercetin, a lead candidate compound.
• Mechanistic studies including assessment of cell proliferation, heterochromatin restoration, and RNA-sequencing.
• Testing quercetin's effects on Hutchinson-Gilford progeria syndrome (HGPS) and naturally aged hMSCs.

Main Results:

• Ten candidate geroprotective compounds were identified from the natural product library.
• Quercetin demonstrated significant geroprotective effects by enhancing cell proliferation and restoring heterochromatin in WS hMSCs.
• RNA-sequencing revealed shared and distinct transcriptional pathways for quercetin and Vitamin C's anti-aging effects.
• Quercetin attenuated senescence in HGPS and physiological aging hMSCs.

Conclusions:

• Quercetin is identified as a potent geroprotective agent effective against both accelerated and natural cellular aging in hMSCs.
• Quercetin's mechanisms involve improving cell proliferation and heterochromatin integrity.
• This study highlights quercetin as a potential therapeutic agent for age-associated disorders.