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Senolytics: Eliminating Zombie Cells

Senolytic drugs target senescent 'zombie cells' that accelerate aging, extending lifespan by 20%+ in animal studies.

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Senolytics: Eliminating Zombie Cells

What Are Senescent Cells?

The Zombie Cell Problem

Normal: Damaged cells → Apoptosis (programmed death) → Cleared Senescent: Damaged cells → Escape death → Accumulate → Secrete toxins

SASP: The Aging Accelerator

Senescent cells release Senescence-Associated Secretory Phenotype (SASP):

  • Pro-inflammatory cytokines (IL-6, IL-1β, TNF-α)
  • Matrix metalloproteinases (tissue degradation)
  • Growth factors promoting cancer
  • Reactive oxygen species

Result: A toxic microenvironment that accelerates aging in surrounding healthy cells.

Landmark Animal Studies

Key Discovery: Eliminating senescent cells extended both lifespan and healthspan

Results:

  • Median lifespan increase: 20%+ in mice
  • Benefits even when treatment started late in life
  • Improved organ function across multiple systems
  • Delayed onset of age-related diseases

Paradigm Shift: Aging isn't just damage accumulation—it's active harm from senescent cells.

Senolytic Compounds

1. Dasatinib + Quercetin (D+Q)

Most studied senolytic combination

Dasatinib: FDA-approved cancer drug, requires prescription Quercetin: Natural flavonoid, over-the-counter

Dosing in Studies:

  • Dasatinib: 100mg
  • Quercetin: 1000mg
  • Frequency: Intermittent (2 days per week or month)

Evidence:

  • Improved walking speed in elderly
  • Reduced senescent cell burden
  • Decreased inflammatory markers

2. Fisetin

Natural senolytic from fruits

Sources: Strawberries (highest), apples, persimmons

Advantages:

  • Available as supplement
  • Generally recognized as safe
  • Dual action: senolytic + antioxidant

Dosing:

  • Research doses: 100-500mg/kg (very high)
  • Human equivalent: ~5-10g for 70kg person
  • Intermittent: 2-3 days per month

Challenge: Requires very high doses, poor bioavailability

3. Rapamycin (Sirolimus)

Dual mechanism: mTOR inhibitor + senescent cell modulator

Status: FDA-approved immunosuppressant, requires prescription

Evidence:

  • Extended lifespan in mice, flies, worms
  • Improved immune function in elderly (clinical trial)
  • May reduce SASP without killing cells (senostatic)

Dosing for Longevity:

  • 1-6mg weekly (much lower than immunosuppressive doses)
  • "Pulse" dosing to minimize side effects

Controversies: Immunosuppressive at high doses, long-term safety unknown

Clinical Applications (Emerging)

Current Trials

  • Idiopathic pulmonary fibrosis (IPF)
  • Osteoarthritis
  • Cardiovascular disease
  • Alzheimer's disease
  • General aging/frailty

Early Results

  • Improved physical function
  • Reduced frailty markers
  • Decreased inflammatory biomarkers
  • Enhanced quality of life

Practical Implementation

Medical Supervision Required

Important: Senolytics (especially prescription) should only be used under medical supervision.

Natural Senolytic Approach

Fisetin Protocol:

  • Dose: 500-1000mg per day for 2-3 days
  • Frequency: Once per month or every other month
  • Form: High-quality supplement
  • Timing: With fatty meal for better absorption

Quercetin Protocol:

  • Dose: 1000mg per day
  • Frequency: Daily or intermittent (2-3 days/week)
  • Enhancement: Combine with bromelain

Supportive Compounds:

  • Curcumin: 500-1000mg daily
  • EGCG: 400-600mg or 3-4 cups green tea
  • Resveratrol: May enhance effects

Clinical Protocols (Physician-Supervised)

D+Q Protocol:

  • Dasatinib: 100mg
  • Quercetin: 1000mg
  • Schedule: 2 consecutive days, every 2-4 weeks
  • Monitoring: CBC, liver function, kidney function

Safety Considerations

Dasatinib Risks:

  • Blood clots (serious risk)
  • Bleeding
  • Cardiovascular events
  • Requires medical monitoring

Quercetin/Fisetin:

  • Generally safe
  • Mild GI upset possible
  • May interact with medications

Key Takeaways

  1. Senescent cells actively accelerate aging—not passive bystanders
  2. Eliminating them extends lifespan 20%+—one of the most robust anti-aging interventions
  3. Benefits even when started late—never too late to clear zombie cells
  4. Human trials are promising—early evidence for improved function
  5. Natural options available—Fisetin, Quercetin accessible without prescription
  6. Medical supervision recommended—especially for Dasatinib, Rapamycin
  7. Intermittent dosing is key—not continuous administration

Actionable Steps

Conservative Approach:

  • Fisetin: 1000mg for 2 days, monthly
  • Quercetin: 500-1000mg daily or intermittent
  • Lifestyle support: Exercise, fasting, sleep
  • Track inflammatory markers

Aggressive Approach (Medical Supervision):

  • Find longevity-focused physician
  • Baseline testing
  • Consider D+Q protocol if appropriate
  • Regular monitoring

Senolytics represent one of the most promising anti-aging interventions. By eliminating zombie cells, we address a fundamental cause of aging—not just symptoms.