FOX04
FOXO4-D-Retro-Inverso
FOXO4-DRI is a synthetic peptide designed to target and remove senescent cells—also known as “zombie cells”—which are old, damaged cells that stop dividing but don’t die off like they should. These cells accumulate with age and release harmful substances that cause chronic inflammation and tissue damage. FOXO4-DRI works by disrupting a specific protein interaction (between FOXO4 and p53), which allows these unhealthy cells to undergo natural cell death (apoptosis) without harming healthy cells.
By clearing out senescent cells, FOXO4 has the potential to reverse signs of aging at the cellular level, improve tissue function, and reduce the burden of age-related diseases. In animal studies, it’s been shown to restore hair growth, increase energy, and improve organ regeneration. While it's still in early research stages and not widely available for clinical use, FOXO4 represents an exciting frontier in the field of senolytics—therapies aimed at slowing or even reversing aging by cleaning out damaged cells.
Protocols
1. Anti-Aging & Longevity (Senescent Cell Clearance & Tissue Rejuvenation)
• Dosage: 3–5 mg per week (subcutaneous or intravenous injection)
• Cycle: Once per week for 4 weeks, followed by a 6–12 month break
Administration: Best taken with fasting or calorie restriction to enhance autophagy
Stacking:
• With Rapamycin or Metformin for synergistic anti-aging effects
• With NMN, Resveratrol, or Fisetin to support NAD+ and mitochondrial function
• With GHK-Cu for enhanced collagen synthesis and skin repair
Expected Benefits:
Reduced inflammation and oxidative stress
Enhanced organ function and cellular repair
Increased tissue regeneration and muscle endurance
2. Muscle Regeneration & Recovery (Athletes & Injury Healing)
• Dosage: 5 mg per week (SC or IV)
• Cycle: 4-week cycle, repeated every 6 months
Administration: Best taken post-exercise or during recovery periods
Stacking:
• With BPC-157 & TB-500 for muscle and tendon healing
• With CJC-1295 & Ipamorelin for GH release and tissue repair
Expected Benefits:
Faster muscle recovery and endurance
Reduced muscle atrophy and stiffness
Enhanced tissue repair and regeneration
3. Neuroprotection & Cognitive Function (Preventing Neurodegeneration)
• Dosage: 3 mg per week (SC or IV)
• Cycle: 4 weeks on, with 6–12 months off
Administration: Best taken with a ketogenic diet or fasting for optimal brain benefits
Stacking:
• With MOTS-c for mitochondrial and brain energy metabolism support
• With Semax or Dihexa for cognitive enhancement
• With Lion’s Mane Mushroom Extract for BDNF upregulation
Expected Benefits:
Reduced brain inflammation and oxidative stress
Improved memory, focus, and cognitive resilience
Lower risk of Alzheimer’s and Parkinson’s disease
4. Metabolic Health & Anti-Inflammatory Benefits
• Dosage: 3–5 mg per week (SC or IV)
• Cycle: 4-week cycle, repeated every 6–12 months
Administration: Best taken while following a low-inflammatory diet (paleo, keto, or fasting protocols)
Stacking:
• With Berberine or AICAR for metabolic regulation
• With Thymosin Alpha-1 (TA-1) for immune modulation
Expected Benefits:
Reduced chronic inflammation and oxidative stress
Improved insulin sensitivity and glucose metabolism
Enhanced mitochondrial function and energy levels
Further reading
FOXO4-DRI belongs to a class of compounds known as senolytics, which are designed to target and remove senescent cells. These cells accumulate in various tissues, contributing to chronic inflammation, metabolic dysfunction, and organ degeneration. FOXO4-DRI selectively disrupts the FOXO4-p53 interaction, causing senescent cells to undergo apoptosis, thereby enhancing tissue regeneration and function.
Animal studies have demonstrated that FOXO4-DRI can reverse many signs of aging, including:
Improved muscle function and endurance
Reduced kidney fibrosis and improved renal function
Enhanced fur density and skin elasticity in aging mice
Increased lifespan and overall resilience
Additionally, FOXO4-DRI has shown promise in preventing neurodegeneration. Since senescent cells contribute to Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, removing them may protect brain function and slow cognitive decline.
Unlike traditional anti-aging drugs that focus on oxidative stress or telomere length, FOXO4-DRI targets cellular senescence at its root cause, offering a fundamentally new approach to longevity and age-related disease prevention.
However, research is still in preclinical stages, and there are no long-term human trials yet. As a result, its safety, long-term effects, and optimal dosing protocols remain under investigation. Despite this, many biohackers and longevity researchers have begun self-experimenting with FOXO4-DRI due to its promising results in animal studies.
References
- Baar, M.P., et al. (2017). Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell, 169(1), 132-147.
Gorgoulis, V., et al. (2019). Cellular senescence in aging and age-related disease: From mechanisms to interventions. Nature Reviews Molecular Cell Biology, 20(8), 402-420.
Childs, B.G., et al. (2020). Senolytics and senostatics: Removing and restraining senescent cells to combat aging and disease. Nature Medicine, 26(8), 1045-1056.
Kirkland, J.L., & Tchkonia, T. (2020). Senolytic drugs: From discovery to translation. Journal of Clinical Investigation, 130(12), 629-641.
van Deursen, J.M. (2021). Senescent cells in aging and disease: A path forward for senolytic therapies. Nature Aging, 1(10), 1086-1099.