Researchers at the University of Dundee introduce a precision senolytic platform that selectively identifies and eliminates senescent cells—damaged “zombie” cells that secrete inflammatory factors—to rejuvenate tissue function and mitigate age-related diseases through targeted biomarker profiling and cellular clearance strategies.
Key points
University of Dundee’s Nature Aging platform uses biomarker-guided senolytic therapies to selectively eliminate senescent cells without collateral tissue damage.
Clinical data with ABT-263 demonstrate accelerated wound healing and reduced inflammatory SASP factors in aged skin models.
Precision senolytic approaches reduce systemic inflammatory burden and improve regenerative responses to mitigate age-related pathologies.
Why it matters:
Precision senolytics represent a paradigm shift in targeting cellular aging, offering measurable tissue rejuvenation and extended healthspan.
Q&A
What are senescent cells?
How do senolytic therapies work?
What is ABT-263 and how does it aid tissue rejuvenation?
What are the safety considerations for senolytic treatments?
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Academy
Cellular Senescence
Cellular senescence is a permanent state of cell cycle arrest that cells enter in response to various stressors such as DNA damage, oxidative stress, or telomere shortening. While senescence initially serves as a beneficial tumor suppressor mechanism by preventing damaged cells from proliferating, the accumulation of senescent cells with age can have detrimental effects on tissue function and organismal health.
Key Features of Senescent Cells:
- Senescence-Associated Secretory Phenotype (SASP): Senescent cells release a mixture of pro-inflammatory cytokines, growth factors, proteases, and other molecules that alter the local and systemic microenvironment.
- Cell Cycle Arrest: These cells permanently exit the cell cycle, yet remain metabolically active and resist apoptotic signals.
- Biomarkers: Common markers include elevated p16^INK4a, p21^CIP1, senescence-associated β-galactosidase activity, and DNA damage foci.
Impact on Aging: The SASP factors secreted by senescent cells contribute to chronic inflammation, extracellular matrix degradation, and impaired stem cell function. This pro-aging environment promotes the development of age-related pathologies such as osteoarthritis, cardiovascular disease, and neurodegeneration.
Senolytics
Senolytics are a class of investigational drugs or molecules designed to selectively eliminate senescent cells while sparing healthy cells. By targeting key survival pathways that are upregulated in senescent cells, senolytics induce apoptosis (programmed cell death) specifically in these dysfunctional cells, thereby reducing their numbers and mitigating SASP-related damage.
Examples of Senolytic Agents:
- ABT-263 (Navitoclax): A BCL-2 family protein inhibitor that disrupts pro-survival signaling in senescent cells, shown to improve wound healing and reduce inflammation in aged skin models.
- Dasatinib + Quercetin: A combination therapy that targets tyrosine kinase pathways and enhances natural flavonoid activity to clear senescent cells in various tissues.
- Fisetin: A plant-derived flavonoid with senolytic activity that has demonstrated reduction of senescent cell burden in preclinical studies.
Mechanism of Action:
- Biomarker Identification: Techniques such as transcriptomic profiling and imaging-based assays are used to detect senescence markers like p16^INK4a and elevated SASP factors.
- Target Engagement: Senolytic compounds bind to anti-apoptotic proteins or other survival regulators preferentially expressed in senescent cells.
- Apoptosis Induction: Once the survival defense is compromised, senescent cells undergo apoptosis and are cleared by the immune system.
- Tissue Rejuvenation: Removal of the pro-inflammatory senescent cell burden restores a healthier microenvironment, encourages stem cell function, and enhances tissue repair.
Clinical Implications: Early human trials for senolytics are exploring treatment of idiopathic pulmonary fibrosis, osteoarthritis, and diabetic complications. Ongoing research aims to refine targeting specificity, optimize dosing regimens, and combine senolytics with other rejuvenation strategies such as stem cell therapies and metabolic modulators.
Future Directions: The integration of AI-driven biomarker analysis and personalized diagnostics promises to tailor senolytic interventions to individual senescent cell profiles. As the field advances, senolytics may become a cornerstone of precision medicine approaches in longevity science, offering the first viable strategy to reverse aspects of biological aging.