LONGEVITY | FOXO3 (rs2802292)

FOXO3 and Healthy Aging: What Your Genotype May Mean

Longevity, or living a long and healthy life, is shaped by many factors including your genes, lifestyle, and environment. One gene that has shown a consistent relationship with lifespan and healthy aging is FOXO3. This gene helps manage cellular repair, reduce inflammation, and protect cells from oxidative stress. Certain variants of FOXO3 are associated with a greater likelihood of living longer and maintaining better health into older age.

How FOXO3 Affects Cellular Health

FOXO3 is a transcription factor. That means it helps turn other genes on or off to control cell processes. Key roles of FOXO3 include:

• Promoting removal of damaged cells and cellular components to keep tissues functioning properly.
• Regulating antioxidant defenses to reduce damage from free radicals.
• Modulating inflammation by influencing inflammatory signaling molecules.
• Supporting repair pathways that preserve cell and tissue resilience.

Variation at a common site in FOXO3, known as rs2802292, has been linked to differences in these protective functions and to observed differences in lifespan in human studies.

General Lifestyle Recommendations to Support FOXO3 Function

Regardless of your FOXO3 genotype, lifestyle choices strongly influence how genes behave. The following evidence-informed strategies support cellular health and may help FOXO3-mediated pathways work optimally:

• Diet: Emphasize a whole-foods approach rich in fruits, vegetables, nuts, seeds, legumes, and fatty fish. Focus on foods high in antioxidants and anti-inflammatory compounds such as berries, leafy greens, turmeric, ginger, and tomatoes.
• Omega-3 fats: Include sources of EPA and DHA like fatty fish or consider a high-quality omega-3 supplement if dietary intake is low.
• Healthy fats: Use extra virgin olive oil and include sources of monounsaturated and polyunsaturated fats.
• Protein: Maintain adequate protein intake to support muscle mass and repair, with attention to lean sources and plant proteins.
• Physical activity: Combine regular aerobic exercise with strength training. Aim for at least 150 minutes per week of moderate activity plus two sessions of resistance exercise.
• Sleep: Prioritize 7 to 9 hours of restorative sleep per night, and maintain consistent sleep timing.
• Stress management: Practice stress reduction techniques such as mindfulness, breathing exercises, yoga, or hobbies that promote relaxation.
• Social connections: Maintain strong relationships and community engagement to support mental and physical health.
• Avoid tobacco and limit alcohol: Smoking and excess alcohol increase cellular damage and inflammation and reduce longevity.
• Regular health checks: Work with your healthcare provider to monitor blood pressure, lipids, glucose, body composition, and inflammation markers as needed.

Dietary and Supplement Considerations

To support antioxidant and anti-inflammatory pathways that interact with FOXO3 activity, consider these practical options:

• Increase intake of colorful fruits and vegetables for vitamins, polyphenols, and carotenoids.
• Include fatty fish like salmon, sardines, and mackerel at least twice weekly or a combined 500 mg to 1000 mg daily of EPA and DHA if using supplements.
• Use spices with anti-inflammatory properties such as turmeric and ginger in cooking.
• Consider a daily multivitamin if dietary gaps exist, focusing on B vitamins, vitamin D, vitamin C, and zinc as appropriate.
• Curcumin, vitamin D, and omega-3 supplements are commonly used to support inflammation balance, but use them under guidance from your healthcare provider.

Monitoring and Tests to Discuss With Your Provider

• Standard metabolic panel including fasting glucose and lipids to assess cardiovascular and metabolic risk.
• High sensitivity C-reactive protein or other inflammation markers if chronic inflammation is a concern.
• Vitamin D level if supplementation is being considered or if deficiency is suspected.
• Body composition and muscle strength assessments to track functional aging.

Genetic Interpretation for rs2802292 (FOXO3)

The section below explains how three possible genotypes at rs2802292 are associated with longevity traits. Use the accordion panels to view the interpretation that applies to you. Remember that genetics is only one piece of the picture and lifestyle and medical care shape actual outcomes.

Final Notes and Disclaimer

PlexusDx provides education about genetic predispositions only. This information is not medical advice. Genetic results can inform lifestyle choices but do not determine your health destiny. Always discuss genetic findings, supplements, major diet changes, or medical concerns with your healthcare provider before making changes to medical or treatment plans.