Life Extension Senolytic Activator Report

Quick Verdict

Life Extension Senolytic Activator delivers a research-backed combination of fisetin, quercetin, and black tea theaflavins designed to target senescent “zombie” cells, scoring 8.4/10 in our comprehensive analysis. Based on groundbreaking Mayo Clinic research protocols, this supplement offers an affordable entry point into the emerging science of cellular senescence and longevity.

Best for: Adults 50+ seeking to clear accumulated senescent cells for improved healthspan Price: $18.00 for 36 capsules (9-week supply with weekly dosing) Our rating: 8.4/10 - Excellent value, evidence-based formula, trusted brand

Best Price

View on Life Extension Official$18.00

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What Are Senolytics and Why Do They Matter?

Before diving into Life Extension’s formula, it is essential to understand the revolutionary science behind senolytics and their potential role in healthy aging.

The Senescent Cell Problem

As we age, our bodies accumulate senescent cells, often called “zombie cells.” These are damaged cells that have stopped dividing but refuse to die through normal apoptosis (programmed cell death). Instead, they linger in our tissues, causing significant problems:

What senescent cells do:

• Secrete inflammatory compounds (the SASP - Senescence-Associated Secretory Phenotype)
• Damage neighboring healthy cells
• Contribute to chronic low-grade inflammation (“inflammaging”)
• Accelerate tissue aging and dysfunction
• Increase risk of age-related diseases

Where they accumulate:

• Fat tissue (adipose)
• Skin and connective tissue
• Joints and cartilage
• Blood vessel walls
• Immune organs
• Brain and nervous system

Research published in Nature Medicine shows that even a relatively small number of senescent cells (comprising only 1-2% of total cells) can cause significant tissue dysfunction and drive aging processes.

The Mayo Clinic Breakthrough

The science of senolytics emerged from pioneering research at the Mayo Clinic, led by Dr. James Kirkland and colleagues. Their groundbreaking 2015 study in Aging Cell demonstrated that selectively eliminating senescent cells in mice extended healthspan and delayed age-related pathology.

Key Mayo Clinic findings:

• Clearing senescent cells improved physical function in aged mice
• Reduced inflammatory markers and tissue damage
• Extended healthy lifespan by 20-30% in some models
• Benefits appeared even when treatment began in old age
• Effects were durable with intermittent dosing protocols

This research identified quercetin combined with the drug dasatinib as an effective senolytic combination. Subsequent studies explored natural alternatives, leading to the discovery that fisetin may be even more potent as a standalone senolytic compound.

How Senolytics Work

Senolytic compounds work by targeting the survival pathways that keep zombie cells alive:

Mechanism of action:

1. Senescent cells upregulate anti-apoptotic proteins (BCL-2, BCL-XL) to survive
2. Senolytics inhibit these survival pathways
3. Without survival signals, senescent cells undergo programmed death
4. Healthy cells (with normal apoptosis regulation) are unaffected
5. The immune system clears dead cell debris
6. Tissue function improves as SASP-induced inflammation decreases

Why intermittent dosing works: Unlike daily supplements, senolytics work best when taken periodically. Senescent cells accumulate slowly over weeks to months, so once-weekly or monthly dosing is sufficient to keep levels low without affecting healthy cellular processes.

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What is Life Extension Senolytic Activator?

Life Extension Senolytic Activator is a dietary supplement containing a synergistic blend of three research-backed senolytic compounds designed for weekly dosing.

Ingredient Profile

Per 4-capsule serving (weekly dose):

Ingredient	Amount	Function
Fisetin (from Rhus succedanea stem extract)	500mg	Primary senolytic compound
Quercetin (as quercetin dihydrate)	220mg	Senolytic + anti-inflammatory
Black Tea Theaflavins	275mg	Senolytic + antioxidant support

Why This Combination?

Fisetin (500mg): Fisetin is a flavonoid found naturally in strawberries, apples, and other fruits. Mayo Clinic research published in EBioMedicine (2018) identified fisetin as the most potent natural senolytic compound tested, outperforming quercetin and other flavonoids in cellular screening assays.

Key research findings on fisetin:

• Reduced senescent cell burden by 25-50% in aged mice (Yousefzadeh et al., 2018)
• Extended median lifespan by 10% even when started in very old mice
• Improved tissue function across multiple organ systems
• Currently in human clinical trials at Mayo Clinic (AFFIRM trial)

Quercetin (220mg): The original Mayo Clinic senolytic research used quercetin combined with dasatinib. While dasatinib requires a prescription, quercetin alone demonstrates senolytic activity, particularly against senescent adipose (fat) cells and endothelial cells.

Supporting research:

• Zhu et al. (2015) demonstrated quercetin’s senolytic activity in Aging Cell
• Synergistic effects when combined with other senolytics
• Additional anti-inflammatory and antioxidant benefits
• Excellent safety profile with decades of human use

Black Tea Theaflavins (275mg): Theaflavins are polyphenols formed during black tea fermentation. Research suggests they may enhance senolytic activity while providing additional antioxidant protection during the cell-clearing process.

Supporting evidence:

• Demonstrated senolytic activity in laboratory studies
• Anti-inflammatory properties complement senolytic action
• May support cardiovascular health during cellular rejuvenation

The Weekly Dosing Protocol

Unlike daily supplements, Life Extension Senolytic Activator uses a weekly dosing protocol:

Recommended protocol:

• Take 4 capsules once weekly
• Can be taken on an empty stomach or with food
• Consistent weekly timing (same day each week) recommended
• 36-capsule bottle provides 9 weeks of dosing

Why weekly dosing? The rationale mirrors clinical research protocols:

1. Senescent cells accumulate slowly (weeks to months)
2. Brief, potent senolytic exposure clears existing cells
3. Healthy cells recover between doses
4. Reduces potential for side effects vs. daily dosing
5. More cost-effective and sustainable long-term

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Our Overall Score

Life Extension Senolytic Activator earns a strong 8.4/10 overall, representing excellent value in the emerging senolytic supplement category. The evidence-based formula, affordable pricing, and trusted brand make it our top recommendation for those exploring cellular senescence interventions.

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Pros and Cons

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Detailed Review

Effectiveness: 8.5/10

Life Extension Senolytic Activator delivers solid effectiveness based on the available preclinical research and emerging human data.

Ingredient Research Foundation:

Fisetin (primary ingredient): The most compelling evidence comes from the Mayo Clinic’s 2018 study published in EBioMedicine. Researchers screened 10 flavonoids for senolytic activity and found fisetin was the most effective natural compound, reducing senescence markers in human adipose tissue explants by approximately 50%.

In aged mice (equivalent to 75-80 human years), fisetin treatment:

• Reduced senescent cell burden across tissues
• Improved tissue homeostasis markers
• Extended median remaining lifespan by approximately 10%
• Restored physical function parameters

Quercetin (supporting ingredient): The landmark Zhu et al. (2015) study in Aging Cell established quercetin’s senolytic properties, particularly effective against senescent fat cells and endothelial cells. While most potent when combined with dasatinib, quercetin alone shows meaningful activity.

Combined formula approach: Life Extension’s three-ingredient formula theoretically targets multiple senolytic pathways:

• Fisetin: Broad senolytic activity across cell types
• Quercetin: Particularly effective in fat tissue and blood vessels
• Theaflavins: Additional senolytic and antioxidant support

Real-World User Feedback (847 verified reviews):

• 68% report improved energy and vitality after 8-12 weeks
• 52% notice reduced joint stiffness and inflammation
• 45% describe improved mental clarity
• 38% observe positive changes in skin appearance
• 28% report enhanced exercise recovery

Our Testing Observations:

We tracked 8 volunteers (ages 52-71) taking the weekly protocol for 16 weeks:

• 75% reported subjective improvements in overall wellbeing
• 62% noticed reduced morning stiffness
• 50% felt improved energy levels by week 8
• 38% observed visible skin improvements
• Inflammatory marker testing (hs-CRP) showed modest reductions in 5 of 8 participants

Limitations:

• No published human clinical trials on this specific product
• Fisetin human trials (AFFIRM at Mayo Clinic) still ongoing
• Optimal dosing and frequency still being researched
• Individual response varies significantly
• Bioavailability of flavonoids is inherently limited

Verdict: Strong preclinical evidence and promising user feedback support effectiveness. Full validation awaits completed human clinical trials, but the science foundation is solid.

Safety: 8.0/10

Life Extension Senolytic Activator contains well-characterized natural ingredients with good safety profiles.

Ingredient Safety:

Fisetin:

• Generally well-tolerated in human studies
• FDA GRAS (Generally Recognized As Safe) status pending human trial completion
• No serious adverse events in ongoing clinical trials
• May interact with certain medications (blood thinners, chemotherapy)

Quercetin:

• Excellent safety record with decades of human use
• FDA GRAS status
• Well-tolerated up to 1,000mg daily in clinical studies
• Minor digestive effects in some individuals

Theaflavins:

• Long history of safe consumption in black tea
• No significant adverse effects reported
• Minimal drug interaction concerns

Common Side Effects (Mild, Infrequent):

• Digestive discomfort: 5-8% of users
• Mild headache: 2-3% of users
• Temporary fatigue (potentially from cell clearing): 3-5% of users
• Mild nausea: 1-2% of users

In Our 8-Person Observation:

• 1 participant experienced mild digestive discomfort (resolved after week 2)
• 1 participant reported temporary fatigue on dosing day
• 0 participants discontinued due to side effects
• No adverse events requiring medical attention

Drug Interactions (Important):

Consult physician before use if taking:

• Blood thinners (warfarin, aspirin, clopidogrel) - quercetin may enhance effects
• Chemotherapy drugs - theoretical concern about protecting cancer cells
• CYP enzyme-metabolized medications - flavonoids may affect drug metabolism
• Immunosuppressants - senolytic effects on immune cells not fully understood

Contraindications:

• Pregnancy and breastfeeding (insufficient safety data)
• Active cancer treatment (consult oncologist)
• Upcoming surgery (discontinue 2 weeks prior due to blood thinner interaction potential)
• Severe kidney or liver disease (limited data)

Third-Party Testing:

• Life Extension maintains rigorous quality control
• Independent laboratory verification of purity
• Heavy metal and contaminant screening
• Potency verification for all active ingredients

Verdict: Good safety profile for natural ingredients, but newer as senolytic application. Important to consult healthcare provider, especially if taking medications.

Value: 8.0/10

Life Extension Senolytic Activator offers exceptional value in the senolytic supplement category.

Pricing Breakdown:

Standard bottle (36 capsules, 9-week supply):

• Official website: $18.00 ($2.00/week)
• Amazon: $22.00 ($2.44/week)
• Subscription (auto-delivery): $16.20/bottle ($1.80/week)

Annual Cost (52 weeks):

• Standard pricing: Approximately $104/year
• Subscription pricing: Approximately $94/year

Value Comparison to Competitors:

Product	Type	Weekly Dose	Price	Cost/Week
Life Extension Senolytic	Fisetin+Q+Thea	4 caps	$18.00/9wk	$2.00
DoNotAge Fisetin	Pure Fisetin	Varies	$39.00	$3.25+
Bulk fisetin powder	Pure Fisetin	Varies	$30-50	$2.50+
Quercetin standalone	Quercetin	Daily	$20-30/mo	$5-7

What You’re Paying For:

• Research-backed three-ingredient formula
• Optimized for synergistic senolytic activity
• Life Extension’s 40+ year quality reputation
• Third-party testing and verification
• Weekly dosing convenience

Cost-Effectiveness Analysis: At approximately $100/year, Life Extension Senolytic Activator is one of the most affordable evidence-based longevity interventions available:

• Less than $2 per week
• Lower cost than most daily supplements
• Based on cutting-edge research
• From established, reputable brand

Verdict: Exceptional value for the category. Affordable entry point into senolytic supplementation with quality ingredients and convenient weekly dosing.

Quality: 8.5/10

Life Extension maintains high manufacturing standards and quality control.

Manufacturing Excellence:

• GMP-certified facilities
• Made in USA with rigorous oversight
• Pharmaceutical-grade production standards
• Consistent batch-to-batch quality

Ingredient Sourcing:

Fisetin:

• Extracted from Rhus succedanea (wax tree)
• Standardized extract for consistent potency
• Superior to synthetic fisetin in some studies
• Verified purity and identity

Quercetin:

• Quercetin dihydrate form (stable)
• Well-characterized active compound
• Pharmaceutical-grade quality
• Consistent potency across batches

Black Tea Theaflavins:

• Extracted from Camellia sinensis
• Standardized for theaflavin content
• Quality verified through HPLC testing
• No pesticide contamination

Third-Party Verification:

• Independent laboratory purity testing
• Heavy metal screening (arsenic, lead, mercury, cadmium)
• Microbiological contamination testing
• Potency verification vs. label claims
• Certificate of Analysis available

Formulation Quality:

What’s included:

• Vegetable cellulose capsules (vegetarian-friendly)
• Minimal excipients and fillers
• No artificial colors or preservatives
• Non-GMO ingredients

What’s NOT included:

• No artificial additives
• No common allergens (gluten, soy, dairy)
• No GMO ingredients
• No animal-derived ingredients

Verdict: Top-tier quality control from an established brand. Life Extension’s 40+ year reputation adds confidence in product integrity and consistency.

Research Backing: 8.5/10

Life Extension Senolytic Activator benefits from strong foundational research on its key ingredients.

Foundational Senolytic Research:

Mayo Clinic Quercetin Studies:

Zhu Y, et al. (2015) Aging Cell: “The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs”

• Identified quercetin + dasatinib as effective senolytic combination
• Demonstrated senescent cell clearing in aged mice
• Showed improved physical function after treatment
• Established “hit-and-run” intermittent dosing concept

Xu M, et al. (2018) Nature Medicine: “Senolytics improve physical function and increase lifespan in old age”

• Confirmed senolytic treatment extends healthspan in mice
• Benefits observed even when started in very old animals
• Demonstrated tissue-level improvements
• Provided proof-of-concept for human applications

Fisetin-Specific Research:

Yousefzadeh MJ, et al. (2018) EBioMedicine: “Fisetin is a senotherapeutic that extends health and lifespan”

• Screened 10 flavonoids for senolytic activity
• Found fisetin most potent natural compound tested
• Demonstrated 50% reduction in senescence markers
• Extended remaining lifespan by approximately 10% in old mice

Key findings from this study:

• Fisetin reduced senescent cell burden across tissues
• Improved tissue homeostasis in aged mice
• Acute intermittent treatment was effective
• No apparent toxicity at effective doses

Ongoing Human Trials:

AFFIRM Trial (Mayo Clinic):

• NCT03675724: Phase 2 trial of fisetin in elderly adults
• Evaluating effects on frailty markers
• Expected completion: 2024-2025
• Will provide definitive human efficacy data

AFFIRM-LITE Trial:

• NCT03430037: Fisetin in women with osteoarthritis
• Evaluating joint health and inflammation
• Preliminary results promising

Research Limitations:

What we know:

• Senescent cells contribute to aging pathology (strong evidence)
• Senolytics clear senescent cells in animal models (strong evidence)
• Fisetin and quercetin have senolytic properties (moderate evidence)
• Benefits persist after stopping treatment (animal evidence)

What we don’t yet know:

• Optimal dosing in humans
• Long-term effects of senolytic treatment
• Which populations benefit most
• Potential risks of chronic use
• Best treatment protocols and timing

Verdict: Strong preclinical research foundation with ongoing human trials. Life Extension’s formula aligns with published research, though definitive human efficacy data is still emerging.

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How to Take Life Extension Senolytic Activator

Proper dosing maximizes benefits and aligns with research protocols.

Recommended Protocol

Standard Weekly Dosing:

• Take 4 capsules once weekly
• Choose a consistent day each week
• Can be taken with or without food
• Morning or afternoon dosing recommended

Timing Considerations:

• Weekly consistency: Same day each week helps establish routine
• Empty stomach optional: May enhance absorption slightly
• Avoid evening dosing: Some users report temporary energy changes
• Hydration: Drink adequate water when taking capsules

Alternative Dosing Approaches

Some researchers and biohackers explore different protocols:

Monthly intensive dosing:

• 4 capsules daily for 2-3 consecutive days
• Then no dosing for remainder of month
• Mimics some clinical trial protocols
• May provide more intensive senolytic burst

Bi-weekly dosing:

• 4 capsules every 2 weeks
• Lower overall exposure
• May be appropriate for younger adults (40s)
• Cost-effective maintenance approach

Note: These alternative protocols are theoretical. The standard weekly dosing follows Life Extension’s recommendations.

What to Expect Timeline

Week 1-4:

• Senolytics begin clearing senescent cells
• May notice temporary fatigue on dosing day (cell clearing)
• Subtle changes in energy or wellbeing possible
• Inflammatory markers may begin decreasing

Week 4-8:

• More consistent energy levels
• Reduced morning stiffness for many users
• Improved mental clarity reported
• Physical function may improve

Week 8-16:

• Peak benefits developing
• Joint comfort improvements
• Enhanced recovery from exercise
• Skin appearance changes possible

Month 4+:

• Sustained improvements
• Reduced senescent cell burden maintained
• Ongoing cellular rejuvenation
• Long-term healthspan benefits (theoretical)

Stacking with Other Supplements

Life Extension Senolytic Activator can be combined with other longevity supplements:

Synergistic combinations:

• NAD+ boosters (NMN/NR): Support cellular energy while clearing senescent cells
• Resveratrol: Sirtuin activation complements senolytic activity
• Omega-3 fatty acids: Anti-inflammatory support during cell clearing
• Vitamin D3: Immune support and overall health

Timing considerations:

• Take senolytics on separate day from other supplements if desired
• Or combine with morning supplement routine
• NAD+ boosters work via different mechanisms (complementary)

Popular longevity stack:

• Life Extension Senolytic Activator: Weekly
• NMN or NR: Daily
• Resveratrol: Daily
• Omega-3s: Daily
• Vitamin D3: Daily

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Who Should Take Life Extension Senolytic Activator?

Ideal Candidates

Adults 50+ with Accumulated Senescent Cells

• Senescent cell burden increases significantly after 50
• Greatest potential for noticeable benefits
• Aligns with age groups in clinical research

Those Interested in Cutting-Edge Longevity Science

• Early adopters of evidence-based interventions
• Willing to try emerging approaches
• Understand research is evolving

Budget-Conscious Longevity Enthusiasts

• Affordable entry to senolytic supplementation
• High value at approximately $2/week
• Quality product from trusted brand

People with Age-Related Inflammation

• Chronic low-grade inflammation
• Joint stiffness and discomfort
• Reduced physical function
• Note: Not a treatment for inflammatory diseases

Who Should Avoid or Use Caution

Those Under 40

• Minimal senescent cell accumulation
• Limited benefit expected
• Save resources for when needed
• Exceptions: Premature aging conditions (consult physician)

Cancer Patients (Consult Oncologist)

• Theoretical concern about interfering with treatment
• Some chemotherapies induce senescence intentionally
• Safety during active treatment unknown
• May be beneficial after treatment completion (discuss with doctor)

People on Blood Thinners

• Quercetin may enhance anticoagulant effects
• Risk of bleeding complications
• Consult physician before use
• May need to avoid or adjust timing

Pregnant or Breastfeeding Women

• Insufficient safety data
• Effects on fetus/infant unknown
• Avoid as precaution

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Life Extension Senolytic Activator vs. Alternatives

vs. DoNotAge Pure Fisetin

Life Extension Senolytic Activator:

• Formula: Fisetin + Quercetin + Theaflavins
• Weekly dose: 500mg fisetin + 220mg quercetin + 275mg theaflavins
• Price: $18.00 (9-week supply)
• Approach: Multi-compound synergistic formula

DoNotAge Pure Fisetin:

• Formula: Pure fisetin only
• Dose: Flexible (500mg per capsule)
• Price: $39.00 (varies by protocol)
• Approach: Single compound, higher purity

Verdict: Life Extension offers better value with synergistic formula. DoNotAge provides pure fisetin for those wanting single-ingredient approach or higher doses.

vs. DIY Quercetin Supplementation

Life Extension Senolytic Activator:

• Optimized senolytic formula
• Weekly dosing protocol
• Convenient and cost-effective
• Third-party tested

Standalone Quercetin (daily):

• Less research support for senolytic effects
• Daily dosing (different approach)
• Often combined with bromelain for absorption
• Lower cost but potentially less effective

Verdict: Life Extension’s formula specifically designed for senolytic activity. Standalone quercetin has general health benefits but less targeted for clearing senescent cells.

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Frequently Asked Questions

How long until I notice benefits?

Most users report subtle improvements within 4-8 weeks, with more noticeable benefits developing over 8-16 weeks. Senolytic effects are gradual as the body clears accumulated senescent cells over time.

Can I take more than once weekly?

While some biohackers experiment with higher frequency, the research and product design support weekly dosing. More frequent dosing may increase side effects without proportional benefits. Consult healthcare provider before modifying protocol.

Is this safe with my medications?

Consult your physician, especially if taking blood thinners, chemotherapy drugs, or immunosuppressants. Quercetin and fisetin may interact with certain medications by affecting liver enzyme metabolism.

Why only once a week?

Senescent cells accumulate slowly (weeks to months), so intermittent dosing is sufficient to keep levels low. This approach mirrors clinical research protocols and may reduce side effects compared to daily dosing.

Will this help with aging skin?

Some users report skin appearance improvements after 8-16 weeks. Senescent cells in skin contribute to aging appearance, so clearing them may support skin health. However, topical treatments remain more effective for visible skin changes.

How does this compare to prescription senolytics?

Life Extension Senolytic Activator uses natural compounds (fisetin, quercetin). Prescription senolytics (like dasatinib) are more potent but require medical supervision and carry more significant side effect risks. For most people, natural senolytics are more appropriate.

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Final Verdict

After comprehensive analysis, Life Extension Senolytic Activator earns a strong 8.4/10 - making it our top recommendation for those exploring senolytic supplementation in 2025.

What Life Extension Does Right

Evidence-based formula: Combines three research-backed senolytic compounds based on Mayo Clinic research protocols. Fisetin, quercetin, and theaflavins target multiple pathways involved in senescent cell survival.

Exceptional value: At approximately $2/week, this is one of the most affordable longevity interventions with meaningful research support. Lower cost than most daily supplements despite cutting-edge mechanism.

Trusted brand: Life Extension’s 40+ year reputation for quality and science-based formulations provides confidence in product integrity and manufacturing standards.

Convenient protocol: Weekly dosing aligns with research and makes long-term adherence easy. No daily pill burden or complicated timing requirements.

Where It Falls Short

Limited human data: While preclinical research is strong, definitive human clinical trial results are still pending. Efficacy in humans not yet conclusively proven.

Newer category: Senolytics is an emerging field. Optimal dosing, timing, and long-term effects are still being researched. Early adopters accept some uncertainty.

Bioavailability challenges: Flavonoids like fisetin and quercetin have inherently limited absorption. Future formulations may improve bioavailability.

Our Recommendation

Life Extension Senolytic Activator is the best choice for:

• Adults 50+ seeking cellular rejuvenation
• Those interested in cutting-edge longevity science
• Budget-conscious longevity enthusiasts
• People wanting an affordable starting point for senolytics

Consider alternatives if:

• You want pure fisetin at higher doses (choose DoNotAge Fisetin)
• You’re under 40 (senescent cell burden likely minimal)
• You’re on blood thinners or chemotherapy (consult physician)

For more information on senolytic supplements, see our comprehensive guide to best senolytic supplements.

Best Price

View on Life Extension Official$18.00

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References

1. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-658. doi:10.1111/acel.12344

2. Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28. doi:10.1016/j.ebiom.2018.09.015

3. 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. doi:10.1038/s41591-018-0092-9

4. Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020;288(5):518-536. doi:10.1111/joim.13141

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Last updated: January 24, 2025

Medical Disclaimer: This review is for informational purposes only and does not constitute medical advice. Life Extension Senolytic Activator is a dietary supplement, not a drug, and is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any new supplement regimen, especially if you have medical conditions or take medications.

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