Researchers at Oxford University and companies such as Insilico Medicine and Calico leverage AI-discovered drug candidates, exposome risk analysis, and epigenetic clocks to advance personalized longevity strategies and target core aging mechanisms.
Key points
Oxford University exposome-wide study shows environmental factors explain 17% of mortality variation versus 2% for genetics.
AI platforms by Insilico Medicine and Calico accelerate discovery of anti-aging compounds through multi-species data modeling.
Senolytic pulse dosing with fisetin and quercetin in early human trials reduces senescent cell burden and chronic inflammation.
Why it matters:
This integrated AI and multi-parameter approach offers a paradigm shift by enabling targeted, preventive interventions with translational potential for age-related diseases.
Q&A
What is the exposome and why does it matter?
How do AI models accelerate drug discovery for aging?
What are epigenetic clocks and how accurate are they?
Why use intermittent dosing for senolytics?
How does prevention differ from reversal in longevity?
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Academy
Senolytics
Senescent cells are damaged or aged cells that no longer divide but remain metabolically active. They accumulate over time in various tissues and release inflammatory factors called the senescence‐associated secretory phenotype (SASP). The SASP can harm neighboring healthy cells, impair tissue repair, and contribute to chronic inflammation and age‐related diseases.
What senolytics are Senolytics are a class of small molecules or biologics designed to selectively induce death of senescent cells. They target survival pathways that senescent cells rely on, such as the BCL‐2 family of proteins, PI3K/AKT signaling, or inflammatory mediators. By clearing these cells, senolytics reduce the SASP burden and improve tissue function.
Key senolytic compounds Common senolytics include natural flavonoids like fisetin and quercetin, and pharmaceuticals such as dasatinib and navitoclax. Fisetin and quercetin inhibit anti–apoptotic BCL‐2 family members, while dasatinib blocks multiple tyrosine kinases. Recent research explores novel agents targeting senescence in specific cell types, such as p16Ink4a‐positive cells.
- Fisetin: A plant flavonoid that triggers apoptosis in senescent adipose and endothelial cells.
- Quercetin: A dietary polyphenol that enhances fisetin’s effect and clears senescent muscle cells.
- Dasatinib: A leukemia drug repurposed to eliminate senescent fibroblasts and stem cells.
Dosing strategies Senolytic protocols often use intermittent or “pulse” dosing to minimize side effects. For example, a common regimen is two consecutive days of dosing per month. This approach allows the body to recover between treatments and avoids chronic drug exposure.
Benefits for longevity Clearing senescent cells improves tissue regeneration, reduces inflammation, and enhances physical performance in animal models. Early human trials show promise in improving measures such as pulmonary function, mobility, and skin health.
Safety and monitoring Although many senolytics are well tolerated, they can cause side effects like fatigue, gastrointestinal discomfort, or cytopenias. Monitoring includes blood tests for liver enzymes, kidney function, and inflammatory markers, as well as tracking symptoms and biomarkers of senescence.
- Assess senescence burden: Measure biomarkers such as p16INK4a expression or SASP factors in blood samples.
- Select a protocol: Choose senolytic agents and dosing schedule based on health status and risk factors.
- Implement treatment: Administer the regimen under medical supervision with periodic monitoring.
- Evaluate outcomes: Track physical performance, inflammatory markers, and organ function over six to twelve months.
Future directions Research aims to develop targeted senolytics that clear senescent cells in specific organs without affecting healthy cells. Advances in drug delivery, such as nanoparticles and tissue‐specific ligands, may increase efficacy and reduce off‐target effects.