Senolytics: Fisetin, NMN, PQQ, and Other Compounds Revolutionizing Anti-Aging

2024-12-26

Background

In 2015, James Kirkland's laboratory at the Mayo Medical Center first discovered that the combination of Dasatinib and Quercetin can selectively induce apoptosis in senescent adipocytes and endothelial cells. Drugs that selectively induce apoptosis in senescent cells are called "senolytics." The Senolytic strategy has been shown to be effective in clearing senescent cells in experimental animals and extending their lifespan.

Senolytics1

Figure: Senolytics selectively kill senescent cells

Key Senolytic Compounds

1. Dasatinib and Quercetin

A pioneering combination, dasatinib (a tyrosine kinase inhibitor) and quercetin (a natural flavonoid) selectively induce apoptosis in senescent fat and endothelial cells, effectively reducing inflammation and promoting tissue health.

2. Fisetin

Found in various fruits and vegetables, fisetin is a powerful antioxidant and anti-inflammatory agent. It enhances apoptotic pathways, clears senescent cells, and supports tissue repair.

3. NMN (Nicotinamide Mononucleotide)

A precursor to NAD+, NMN boosts cellular energy, improves mitochondrial function, and facilitates DNA repair, making it critical for metabolic health and aging intervention.

4. PQQ (Pyrroloquinoline Quinone)

This vitamin-like compound promotes mitochondrial biogenesis and offers strong antioxidant protection. PQQ enhances brain health, cardiovascular function, and cellular repair.

5. ABT-263 (Navitoclax)

A Bcl-2 family inhibitor, ABT-263 triggers apoptosis in senescent fibroblasts. While effective, its clinical use is limited by side effects like thrombocytopenia.

6. EF24

A curcumin derivative, EF24 demonstrates broad senolytic activity by inhibiting NF-κB and ROS pathways. It also shows potential in treating cancers and aging-related conditions.

7. EGCG (Epigallocatechin Gallate)

Extracted from green tea, EGCG combats oxidative stress, reduces cellular senescence, and improves metabolic and cardiovascular health.

Figure: The main metabolic pathways of NMN and NAD+ in the human body

8. Piperlongumine

Derived from long pepper, piperlongumine induces oxidative stress selectively in cancer and senescent cells, inhibiting tumor growth with minimal systemic toxicity.

The Future of Anti-Aging Science

Senolytic compounds are redefining aging interventions, offering promising solutions for cellular repair, chronic disease prevention, and healthspan extension. These advancements bring us closer to transformative therapies for aging-related challenges.