The theory of aging by autodigestion, as explored in this PLOS ONE paper, proposes that aging results from the gradual damage to tissues caused by the body’s own digestive enzymes, primarily those released from the pancreas. This idea builds on observations that, in older organisms, these enzymes (like trypsin) can escape the gastrointestinal system and infiltrate other tissues. This infiltration results in progressive tissue degradation over time.

Key findings supporting this theory include:

1. Enzyme Distribution and Accumulation: In older tissues outside the gastrointestinal tract (e.g., liver, heart, brain), there is increased presence and activity of pancreatic digestive enzymes. This accumulation correlates with signs of tissue degradation.

2. Collagen Damage: Digestive enzymes can break down extracellular matrix components like collagen, leading to weakened structural integrity in tissues.

3. Mechanistic Insights: The study hypothesizes that this autodigestion process begins due to a failure of normal containment mechanisms for digestive enzymes, such as protective barriers in the gut.

4. Potential Links to Aging Hallmarks: The tissue damage from autodigestion could interact with or exacerbate other hallmarks of aging, including chronic inflammation, genomic instability, and cellular senescence.

This framework offers a novel perspective on aging, complementing other theories by focusing on the internal biochemical environment rather than solely genetic or environmental factors.

Combating this involves strategies that support cellular health, reduce oxidative damage, and maintain metabolic and immune balance:

1. Promote Healthy Mitochondrial Function

• Exercise: Regular physical activity enhances mitochondrial biogenesis and function.
• Dietary Support: Consume foods rich in mitochondrial-supporting nutrients like CoQ10, carnitine, and B vitamins.
• Intermittent Fasting: Short-term fasting can promote mitophagy, removing damaged mitochondria.

2. Enhance Autophagy (Cellular Cleanup)

• Caloric Restriction: Reducing calorie intake without malnutrition has been shown to enhance autophagy.
• Phytochemicals: Compounds like resveratrol, curcumin, and EGCG (from green tea) can promote autophagy.
• Exercise: Physical activity also stimulates autophagy pathways.

3. Reduce Oxidative Stress

• Antioxidant-Rich Diet: Include foods high in antioxidants, such as berries, leafy greens, nuts, and seeds.
• Supplementation: Consider supplements like vitamin C, vitamin E, alpha-lipoic acid, and glutathione precursors (e.g., N-acetylcysteine).
• Avoid Toxins: Minimize exposure to environmental toxins and pollutants that increase oxidative stress.

4. Maintain Immune Balance

• Anti-Inflammatory Foods: Include omega-3 fatty acids (from fish or flaxseed) and spices like turmeric to combat chronic inflammation.
• Healthy Gut Microbiome: Probiotics, prebiotics, and a fiber-rich diet help maintain immune homeostasis.

5. Support Cellular Repair Mechanisms

• NAD+ Boosters: Supplements like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) can replenish NAD+ levels, critical for DNA repair and energy metabolism.
• DNA Repair Nutrients: Zinc, selenium, and folate support DNA repair enzymes.

6. Hormesis and Resilience Training

• Cold and Heat Stress: Practices like cold water immersion and sauna therapy can stimulate cellular stress responses that enhance resilience.
• Moderate Stress Exposure: Controlled stressors, such as short fasting periods or high-intensity exercise, can help cells adapt to challenges.

7. Lifestyle Optimization

• Sleep: Prioritize quality sleep, as repair and detoxification processes are most active during this time.
• Stress Reduction: Chronic stress accelerates cellular aging; practice mindfulness, yoga, or meditation.
• Avoid Smoking and Limit Alcohol: These habits greatly accelerate oxidative damage and inflammation.

8. Medical Interventions

• Senolytics: Compounds that target and eliminate senescent (damaged) cells, such as quercetin and dasatinib, are a promising area of research.
• Metformin: May help reduce oxidative stress and improve metabolic health.
• Rapamycin: Inhibits mTOR, promoting autophagy and potentially extending healthspan.

These interventions, when combined, can address the root causes of cellular damage associated with aging and slow down the processes contributing to "autodigestion."