Rejuvenate (Senolytic)

Rejuvenate — Advanced Senolytic & Cellular Renewal Support

Aging happens cell by cell. Rejuvenate targets the cells that have stopped functioning — and started causing harm.*

As the body ages, a growing proportion of cells enter a state of cellular senescence — losing the ability to divide or function normally while simultaneously releasing a cascade of pro-inflammatory signals known as the senescence-associated secretory phenotype (SASP). These "zombie cells" don't just stop working. They actively secrete factors that damage neighboring healthy cells, impair tissue regeneration, promote chronic low-grade inflammation, and accelerate the aging process in the tissues surrounding them.*

Senolytic science — the study of selectively clearing senescent cells — is one of the most active and promising areas of longevity research. Rejuvenate was designed around its best-studied natural compounds: fisetin, Quercetin Phytosome®, and a multi-layered supporting cast of SASP modulators, autophagy activators, and antioxidant defenders.*

Administered as a once-weekly high-dose pulse — mirroring the dosing architecture used in clinical senolytic research — Rejuvenate delivers a concentrated senotherapeutic intervention designed for practitioners who understand what happens at the cellular level when aging is addressed at its source.*

KEY SUPPORTED BENEFITS

Rejuvenate is formulated to support:*

• Natural clearance of senescent cell burden — the cellular aging process that drives "inflammaging"*
• Healthy SASP modulation — reducing the inflammatory signaling that senescent cells secrete*
• Autophagy activation — cellular recycling and self-renewal*
• Mitochondrial energy production, resilience, and cellular repair*
• NAD+ homeostasis through CD38 modulation*
• Muscle performance, recovery resilience, and mitochondrial renewal in muscle tissue*
• Broad-spectrum antioxidant defense — oxidative stress, lipid peroxidation, and free radical neutralization*
• Healthy inflammatory response signaling and cellular detoxification*
• Nutrient bioavailability and absorption optimization*

THE SENOLYTIC SCIENCE — WHY SENESCENT CELLS MATTER

Understanding What Rejuvenate Is Designed to Do

Every tissue in the body continuously produces new cells to replace aging ones. But as we age, an increasing number of cells enter a permanent growth arrest state — cellular senescence — instead of dying through normal apoptosis. They persist in tissues, consuming resources and producing SASP factors: cytokines, chemokines, proteases, and growth factors that create a pro-inflammatory, pro-aging microenvironment.*

Three core problems of cellular aging that accumulate over time:

Senescent Cell Accumulation: Zombie cells build up across tissues — adipose tissue, liver, kidney, vasculature, brain, lung, and muscle — driving tissue dysfunction in a tissue-specific pattern that varies by individual and accumulates exponentially with age.*

SASP Signaling Disruption: The inflammatory cascade secreted by senescent cells damages neighboring healthy cells, suppresses their function, and can even induce senescence in previously healthy cells — a process sometimes called "bystander senescence."* This self-amplifying dynamic is why senescent cell burden accelerates with age rather than remaining linear.*

Declining Cellular Turnover: As senescent cells accumulate and SASP signaling increases, autophagy declines, mitochondrial function weakens, and the tissue's regenerative capacity diminishes — creating a feedback loop between cellular aging, inflammation, and declining function.*

The Senolytic Approach: Rather than managing the downstream consequences of senescent cell accumulation, senolytics target the upstream cause — supporting the selective clearance of senescent cells to reduce their burden, moderate SASP signaling, and create the cellular environment in which healthy regeneration can occur.*

ONCE-WEEKLY PULSE DOSING — AND WHY IT MATTERS

Most longevity supplements are taken daily. Rejuvenate uses a once-weekly pulse protocol — and that distinction is clinically important.*

Senescent cells take time to re-accumulate after clearance support. Daily senolytic dosing is not more effective and may reduce efficacy by interfering with normal cellular signaling between pulse events. The intermittent pulse architecture — mirroring the dosing strategy used in published human senolytic research — allows for a high-concentration senolytic event followed by a recovery period in which cleared cellular space can be repopulated by healthier cells.*

This is not a compromise — it is the correct clinical approach for this class of ingredients.*

THE FORMULA — TEN INGREDIENTS. ONE SENOLYTIC SYSTEM.

Fisetin

Role: Primary Senolytic Support — Natural Senescent Cell Burden Reduction

Fisetin is a naturally occurring polyphenol found in strawberries, apples, grapes, and onions — and the most potent natural senolytic compound in the published longevity research literature.* It is the subject of active human clinical investigation across multiple Mayo Clinic trials and independent research centers, making it the most clinically studied natural senolytic ingredient currently available.*

Fisetin's proposed senolytic mechanism involves selective activation of apoptotic pathways in senescent cells — exploiting the pro-survival signaling that senescent cells depend on (particularly the Bcl-2 family anti-apoptotic proteins) to selectively induce their clearance while leaving healthy cells unaffected.* This selectivity is the defining feature of a true senolytic compound.*

Preclinical Evidence: Fisetin has demonstrated robust senolytic and lifespan-extending effects in multiple rodent studies — reducing senescent cell burden in adipose, liver, brain, and vascular tissue, and extending median lifespan in aged mice.* In vitro, fisetin outperformed 10 other flavonoids as a senolytic across multiple cell types.*

Human Clinical Evidence — Emerging and Ongoing:*

• Mayo Clinic AFFIRM trial (NCT03430037): Fisetin at 20 mg/kg/day for 2 days evaluated as a senolytic for frailty and inflammation in elderly women with multi-morbidity — actively enrolling and ongoing*
• Mayo Clinic STOP-Sepsis trial (NCT05758246): Multi-center randomized, double-blind, adaptive allocation Phase 2 trial evaluating fisetin in 220 elderly sepsis patients, with quantification of senescent CD3+ cells as a secondary outcome*
• 2024 Mayo Clinic long-COVID observational study (536 patients): 44 patients receiving fisetin reported significant alleviation of symptoms including fatigue, muscle pain, and orthostatic hypotension (64% response rate)*
• NCT06431932: Pilot trial of fisetin in healthy volunteers and older patients with multimorbidity — investigating pharmacokinetics, safety, and senolytic biomarkers*
• At Rejuvenate's once-weekly pulse dose, fisetin is delivered at a concentration consistent with the research literature supporting its senolytic activity.*

Quercetin Phytosome® (Quercefitᵀᴹ)

Role: Senolytic Support, Antioxidant Defense & Vascular Integrity — Enhanced Bioavailability

Quercetin is one of the most broadly studied dietary flavonoids — with documented activity as a senolytic agent, antioxidant, anti-inflammatory signaling modulator, and vascular protective compound.* In the senolytic literature, quercetin has been studied extensively alongside dasatinib (D+Q) in Mayo Clinic human trials — where the D+Q combination demonstrated reduced adipose tissue senescent cell burden measured by p16INK4a and SA-βGal markers, along with improved physical function in IPF patients.*

The challenge with standard quercetin is bioavailability — quercetin aglycone is poorly water-soluble and poorly absorbed in conventional oral forms.*

Rejuvenate uses Quercetin Phytosome® (Quercefitᵀᴹ) — quercetin complexed with lecithin phospholipids at the molecular level through Indena's proprietary Phytosome® technology. A 2024 systematic review and meta-analysis of 31 human intervention studies confirmed that lecithin phytosome formulation achieves up to 20-fold higher quercetin bioavailability compared to standard quercetin aglycone.*

At equivalent senolytic doses, Quercetin Phytosome® delivers meaningfully more active quercetin to systemic circulation — making the senolytic activity per gram administered substantially greater than standard quercetin.*

Quercetin Phytosome® also carries clinical evidence for:*

• Antioxidant protection and healthy inflammatory response modulation*
• Vascular integrity support and endothelial function*
• Healthy uric acid metabolism (2025 published human study)*
• Lipid metabolism support (2025 published human clinical study)*
• Broad antiviral and immune-modulatory activity*

Spermidine (Puremidine®) — 10 mg

Role: Autophagy Activation, Cellular Renewal & Longevity Signaling

Spermidine in Rejuvenate serves as the autophagy activation complement to fisetin and quercetin's senolytic activity. While senolytics target the clearance of existing senescent cells, autophagy ensures the continuous recycling of damaged cellular components before they accumulate — addressing cellular aging proactively rather than reactively.*

At 10 mg Puremidine® per weekly serving, Rejuvenate delivers a high-dose spermidine pulse alongside the senolytic ingredients — consistent with the emerging understanding that autophagy activation and senolytic clearance are complementary rather than competing strategies for cellular longevity.*

Spermidine's 2025 human clinical evidence — including the POLYCAD cardiac aging trial, the Aging journal study reversing memory decline, and the vaccine immune response trial — is described in full on the Prime Time+ product page, where Puremidine® also features as a daily formula ingredient.*

Senactiv® (Panax notoginseng Root + Rosa roxburghii Fruit Extracts)

Dose: 50 mg Role: Muscle Senolytic Renewal, Mitochondrial Energy & Recovery Support 

Senactiv® is the first and only natural ingredient backed by human studies demonstrating senescent cell clearance specifically in muscle tissue — through phagocytic macrophage activation during and after exercise.*

In 9 of 12 human subjects, Senactiv® supplementation led to complete elimination of senescent muscle cells following high-intensity interval training — allowing new, metabolically active muscle cells with greater mitochondrial density, ATP production capacity, and glycogen storage potential to regenerate in their place.*

In the context of Rejuvenate's senolytic architecture, Senactiv® provides a tissue-targeted senolytic mechanism specific to muscle — addressing the muscle-specific cellular aging that systemic senolytics like fisetin and quercetin may not reach as efficiently.*

Additional Senactiv® clinical evidence:*

• 47% increase in citrate synthase activity — a direct mitochondrial energy production marker*
• 2.7x greater muscle glycogen accumulation versus control*
• Significant improvement in endurance performance and time to exhaustion*
• Significant reduction in inflammatory and oxidative biomarkers post-exercise*

TurmiPure GOLD® (Micellar Curcumin Complex) + CurcuPrime® (Tetrahydrocurcumin)

Role: SASP Inflammatory Modulation, Cellular Detoxification & Antioxidant Defense — Dual High-Bioavailability Turmeric Complex

Rejuvenate's dual turmeric complex addresses the SASP inflammatory signaling that senescent cells generate — working downstream of fisetin and quercetin's senolytic activity to modulate the inflammatory environment created by residual senescent cells.*

TurmiPure GOLD® is a micellar curcumin formulation from Givaudan — delivering the curcuminoid complex in self-assembling micelles that dramatically improve solubility and absorption. A completed randomized crossover pharmacokinetic trial demonstrated 24-fold higher curcuminoid bioavailability over 24 hours compared to standard turmeric extract.* At 300 mg of TurmiPure GOLD®, Rejuvenate delivers curcuminoid exposure equivalent to over 7g of standard turmeric extract.*

CurcuPrime® delivers tetrahydrocurcumin (THC) — the primary active metabolite that curcumin is converted to in the body, delivered directly for consistent and predictable bioavailability. Tetrahydrocurcumin provides:*

• More potent antioxidant activity than curcumin itself (greater DPPH radical scavenging capacity)*
• Cellular detoxification support through phase II enzyme induction*
• SASP modulation through NF-κB pathway support*
• Superior metabolic stability compared to parent curcumin*

Together, TurmiPure GOLD® and CurcuPrime® provide complementary curcuminoid activity — TurmiPure GOLD® for rapid-onset anti-inflammatory signaling and CurcuPrime® for sustained antioxidant defense and detoxification support.

MitoPrime® L-Ergothioneine — 25 mg

Role: Mitochondrial Neuroprotection, Cellular Antioxidant Accumulation & Longevity Defense 

L-Ergothioneine — the "longevity vitamin" — accumulates selectively in the mitochondria and high-metabolic tissues that bear the greatest oxidative burden from SASP inflammatory signaling and cellular aging. At 25 mg in Rejuvenate's weekly pulse, MitoPrime® provides concentrated neuroprotective and mitochondrial antioxidant support in the cellular environment created by Rejuvenate's senolytic activity.*

Apigenin & Luteolin

Role: NAD+ Conservation via CD38 Modulation & Complementary Antioxidant Defense

Apigenin supports NAD+ homeostasis by modulating CD38 — the primary enzyme responsible for NAD+ degradation. By conserving endogenous NAD+, apigenin supports the sirtuin and PARP longevity signaling pathways that depend on NAD+ availability — and that are particularly relevant in the cellular environment following senolytic clearance, when regenerating cells require NAD+ for metabolic activity and DNA repair.*

Luteolin provides neuro-vascular antioxidant defense, healthy inflammatory tone, and direct autophagy support — reinforcing both Rejuvenate's cellular renewal and inflammatory modulation pillars.*

EGCG (Epigallocatechin Gallate, from Green Tea Extract)

Role: Cellular Metabolism, Stress Resilience & Broad-Spectrum Senescence Modulation

EGCG is the primary bioactive catechin of green tea — one of the most studied plant polyphenols in cellular aging and longevity science, with documented activity across multiple senescence-related pathways.* EGCG supports autophagy signaling, healthy inflammatory balance, cellular metabolism, and antioxidant defense — completing Rejuvenate's broad-spectrum polyphenol senolytic support network.*

In the context of Rejuvenate's once-weekly pulse, EGCG's rapid-acting antioxidant and signaling activity provides immediate cellular protection during the senolytic event.*

AstraGin® (Astragalus membranaceus + Panax notoginseng Root Extracts)

Dose: 50 mg Role: Bioavailability Optimization & Absorption Enhancement

AstraGin® upregulates key intestinal nutrient transporter proteins — SGLT-1, PEPT1, and CAT1 — supporting the absorption and bioavailability of Rejuvenate's active polyphenol compounds. In a formula where every active ingredient operates at a once-weekly high-dose pulse, maximizing the absorption of each component is directly relevant to clinical efficacy.*

AstraGin® also contributes gut barrier integrity support and immune homeostasis — complementary to the systemic cellular renewal goal of the formula.*

Science-Backed Longevity Synergy

Rejuvenate integrates ten complementary mechanisms to help maintain healthy cellular function:

• Senolytic support to promote the natural clearance of aged cells*

• Autophagy induction for cellular recycling and renewal*

• Antioxidant defense to reduce oxidative burden*

• Mitochondrial support for energy and resilience*

• Inflammatory balance for systemic health and performance*

Together, these ingredients deliver comprehensive support for the biological systems most affected by time and stress—helping your cells feel younger, stronger, and more efficient.