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Exposome and Healthspan

Introduction: The term exposome describes the totality of environmental and lifestyle factors that an individual encounters during their lifetime, from diet and pollutants to physical activity and stress. Unlike genetics, which is fixed at birth, the exposome is dynamic and modifiable, making it a key concept for understanding and improving healthspan—the period of life spent in good health.

Key Components of the Exposome

• Dietary Exposures: Nutrients (vitamins, minerals), fats, and phytochemicals can impact metabolic pathways and aging mechanisms.
• Environmental Pollutants: Heavy metals (lead, arsenic, cadmium), air pollutants, and chemicals disrupt cellular processes and accelerate aging.
• Lifestyle Factors: Smoking, alcohol, and physical activity levels influence oxidative stress, inflammation, and repair mechanisms.
• Psychosocial Stress: Chronic stress alters hormonal balance and inflammatory responses, affecting longevity.

Oxylipin Metabolism and Its Role in Aging

Oxylipins are signaling lipids derived from polyunsaturated fatty acids (PUFAs). Enzymes such as:

• Cytochrome P450s (CYP) produce epoxy- and hydroxy-PUFAs.
• Lipoxygenases (LOX) generate leukotrienes and hydroperoxides.
• Cyclooxygenases (COX) form prostaglandins and thromboxanes.

These mediators regulate inflammation, vascular function, and cell survival. Imbalances in oxylipin profiles, driven by exposome factors, contribute to chronic inflammation and cellular senescence—a hallmark of aging.

Interplay Between Exposome and Oxylipins

• Vitamin-Modulated Oxidative Stress: Adequate levels of vitamins A, D, E, and K support antioxidant defenses, reducing lipid peroxidation and harmful oxylipin formation.
• Metal Exposure: Heavy metals disrupt enzymatic pathways (CYP, LOX), leading to pro-inflammatory oxylipin accumulation and senescence.
• PUFA Availability: Dietary omega-3 and omega-6 intake influences substrate pools for oxylipin synthesis, affecting inflammatory balance.

Strategies to Enhance Healthspan

Research points to targeted interventions such as inhibiting soluble epoxide hydrolase (sEH) to preserve beneficial epoxy-PUFAs, dietary optimization of PUFAs, and reducing pollutant exposure. By modulating the exposome and oxylipin metabolism, it may be possible to slow down cellular aging, decrease chronic inflammation, and extend the healthy years of life.

Future Directions

1. Develop personalized exposome profiles to guide nutrition and lifestyle choices.
2. Explore small-molecule inhibitors of key lipid-metabolizing enzymes in clinical trials.
3. Integrate exposome monitoring with wearable sensors for real-time healthspan management.