¶ Cellular Senescence Interventions
Cellular senescence interventions target senescent cells, which accumulate with age and contribute to tissue dysfunction and chronic inflammation. These interventions aim to remove or modulate senescent cells to improve healthspan and potentially extend lifespan.
¶ Overview
Senescent cells are cells that have stopped dividing but remain metabolically active, secreting harmful factors that contribute to aging. Removing these cells or preventing their accumulation may slow aging processes.
¶ Types of Interventions
¶ Senolytic Drugs
- Dasatinib and quercetin combination
- Fisetin and other flavonoids
- BCL-2 inhibitors
- p53 pathway modulators
¶ Senomorphic Agents
- Rapamycin and mTOR inhibitors
- Metformin
- Anti-inflammatory compounds
- Antioxidant therapies
¶ Emerging Approaches
- CAR-T cell therapy for senescent cells
- Antibody-based targeting
- Gene therapy approaches
- Immunotherapy strategies
¶ Mechanism of Action
These interventions work through:
- Selective elimination of senescent cells
- Reduction of senescence-associated secretory phenotype (SASP)
- Decreased inflammation
- Improved tissue function
- Enhanced regeneration capacity
¶ Clinical Evidence
Current evidence includes:
- Promising animal studies
- Limited human trials
- Improvements in healthspan markers
- Ongoing clinical research
Studies in mice have shown that senolytic drugs can improve physical function and extend lifespan in old age.[1] A clinical trial demonstrated that the combination of dasatinib and quercetin reduced senescent cell burden and improved physical function in patients with idiopathic pulmonary fibrosis.[2]
¶ Safety Considerations
Potential risks include:
- Off-target effects
- Tissue damage from senescent cell removal
- Immune system effects
- Unknown long-term consequences
¶ See also
¶ References
Xu M, Pirtskhalava T, Farr JN, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246-1256. https://www.nature.com/articles/s41591-018-0092-9 ↩︎
Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554-563. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(19)30094-0/fulltext ↩︎