Description: <b>Regular physical activity</b> has been shown to influence cancer risk, progression, and survivorship. While exercise is not a cure for cancer, extensive research indicates that it can help reduce the risk of developing certain types of cancer and improve outcomes and quality of life for those diagnosed.<br>
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-Lowering the levels of hormones levels.<br>
-Preventing high blood levels of insulin.<br>
-Regular physical activity leads to decreased levels of inflammatory markers (such as C-reactive protein and interleukin-6).<br>
-Improving immune system function (enhancing the circulation of immune cells, including natural killer cells, T lymphocytes, and macrophages)<br>
-Reducing the time it takes for food to travel through the digestive system.<br>
-Helping to prevent obesity, which is a risk factor for many cancers.<br>
-Exercise promotes the upregulation of antioxidant defenses.<br>
<pre>
Exercise simultaneously modulates multiple core cancer drivers:
↓ Insulin / IGF-1 signaling
↓ Chronic inflammation (IL-6, TNF-α baseline)
↑ Immune surveillance (NK cells, CD8⁺ T cells)
↑ Mitochondrial function and mitophagy
↓ Estrogen and androgen bioavailability
↑ Circadian stability
↓ Visceral adiposity (key endocrine organ)
No supplement or single molecule does this breadth of work.
Exercise, fasting, and diet work by changing the environment tumors depend on — not by poisoning the tumor.
Age-stratified interpretation
1. Younger / metabolically healthy adults
-Baseline IGF-1: normal–high
-Exercise effect:
-Systemic IGF-1 ↔ or slight ↓
-IGF-1 signaling efficiency ↑ (better receptor sensitivity)
-Net effect:
-Less chronic growth drive
-Better metabolic control
➡ This is where IGF-1 ↓ papers usually come from.
2. Older adults (≈50–60+ years)
-Baseline IGF-1: low
-Exercise effect:
-IGF-1 ↑ (restoration toward youthful range)
-Improved GH → IGF-1 axis responsiveness
-Net effect:
-Muscle, bone, immune maintenance
-Reduced frailty and inflammation
➡ This is where IGF-1 ↑ papers come from.
3. Cancer relevance (critical distinction)
-Even when circulating IGF-1 increases in older exercisers:
-Tumor IGF-1 signaling still goes DOWN, because:
-Insulin sensitivity improves
-IGFBP balance shifts
-Inflammation drops
-mTOR tone is suppressed
-AMPK tone is elevated
So:
-Host IGF-1 ↑ ≠ tumor IGF-1 signaling ↑
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Exercise — Cancer vs Normal Cell Effects
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>Label</th>
<th>Primary Interpretation</th>
<th>Notes</th>
</tr>
<tr>
<td>1</td>
<td>Insulin / IGF-1 signaling</td>
<td>↓ IGF-1 signaling (tumor context)</td>
<td>↑ or ↓ IGF-1 (age- and baseline-dependent normalization)</td>
<td>Driver</td>
<td>Growth-signal reprogramming</td>
<td>Exercise normalizes IGF-1 toward age-appropriate levels while reducing tumor-promoting signaling</td>
</tr>
<tr>
<td>2</td>
<td>AMPK → mTOR nutrient sensing</td>
<td>↑ AMPK; ↓ mTOR (growth restraint)</td>
<td>↑ AMPK; ↓ mTOR (metabolic optimization)</td>
<td>Driver</td>
<td>Energy-sensing reprogramming</td>
<td>Repeated AMPK activation enforces catabolic signaling incompatible with tumor anabolism</td>
</tr>
<tr>
<td>3</td>
<td>Immune surveillance (NK cells, T cells)</td>
<td>↑ immune-mediated tumor pressure</td>
<td>↑ immune competence</td>
<td>Driver</td>
<td>Enhanced antitumor immunity</td>
<td>Exercise mobilizes NK cells and improves immune trafficking into tumors</td>
</tr>
<tr>
<td>4</td>
<td>Mitochondrial metabolism / metabolic flexibility</td>
<td>↓ metabolic advantage</td>
<td>↑ mitochondrial capacity and flexibility</td>
<td>Secondary</td>
<td>Energy efficiency divergence</td>
<td>Normal cells adapt metabolically; cancer cells lose relative advantage</td>
</tr>
<tr>
<td>5</td>
<td>Reactive oxygen species (ROS)</td>
<td>↑ ROS (secondary, transient)</td>
<td>↑ transient ROS → adaptive signaling</td>
<td>Secondary</td>
<td>Hormetic redox signaling</td>
<td>Exercise induces transient ROS that act as signals rather than toxins</td>
</tr>
<tr>
<td>6</td>
<td>Glutathione (GSH) and antioxidant capacity</td>
<td>↔ or insufficient upregulation</td>
<td>↑ GSH and antioxidant enzymes</td>
<td>Adaptive</td>
<td>Redox resilience in normal tissue</td>
<td>Normal cells adaptively increase antioxidant defenses; tumors adapt poorly</td>
</tr>
<tr>
<td>7</td>
<td>NRF2 antioxidant response</td>
<td>↔ modest activation</td>
<td>↑ NRF2 (adaptive)</td>
<td>Adaptive</td>
<td>Stress adaptation</td>
<td>NRF2 supports recovery and resilience rather than cytotoxicity</td>
</tr>
<tr>
<td>8</td>
<td>Inflammatory signaling (NF-κB / cytokines)</td>
<td>↓ pro-tumor inflammation</td>
<td>↓ chronic inflammation</td>
<td>Secondary</td>
<td>Anti-inflammatory milieu</td>
<td>Exercise reduces chronic low-grade inflammation that supports tumor progression</td>
</tr>
<tr>
<td>9</td>
<td>Cell cycle / proliferation</td>
<td>↓ proliferation (indirect)</td>
<td>↔ normal turnover</td>
<td>Phenotypic</td>
<td>Growth restraint</td>
<td>Proliferation effects arise from upstream hormonal and metabolic changes</td>
</tr>
</table>
<br>
<hr>
<br>
Exercise — Alzheimer’s Disease & Cognitive Decline
<table border="1" cellspacing="0" cellpadding="4">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Direction</th>
<th>Label</th>
<th>Primary Interpretation</th>
<th>Key Cognitive / AD Relevance</th>
<th>Notes</th>
</tr>
<tr>
<td>1</td>
<td>BDNF / TrkB neurotrophic signaling</td>
<td>↑ BDNF</td>
<td>Driver</td>
<td>Synaptic plasticity and neuronal survival</td>
<td>Improves learning, memory consolidation, and hippocampal resilience</td>
<td>BDNF induction is the single most robust and reproducible neurocognitive effect of exercise</td>
</tr>
<tr>
<td>2</td>
<td>Neurogenesis (hippocampal dentate gyrus)</td>
<td>↑ neurogenesis</td>
<td>Driver</td>
<td>Structural cognitive reserve</td>
<td>Supports memory formation and delays cognitive decline</td>
<td>Adult hippocampal neurogenesis is exercise-responsive and BDNF-dependent</td>
</tr>
<tr>
<td>3</td>
<td>Cerebral blood flow / angiogenesis (VEGF)</td>
<td>↑ perfusion</td>
<td>Driver</td>
<td>Improved nutrient and oxygen delivery</td>
<td>Enhances executive function and processing speed</td>
<td>Vascular health strongly predicts AD progression</td>
</tr>
<tr>
<td>4</td>
<td>Mitochondrial biogenesis (PGC-1α)</td>
<td>↑ mitochondrial capacity</td>
<td>Driver</td>
<td>Energy resilience in neurons</td>
<td>Preserves synaptic function and neuronal firing reliability</td>
<td>Mitochondrial dysfunction is an early AD feature</td>
</tr>
<tr>
<td>5</td>
<td>Neuroinflammation (microglia, cytokines)</td>
<td>↓ chronic inflammation</td>
<td>Driver</td>
<td>Microglial normalization</td>
<td>Reduces neurotoxic inflammatory signaling linked to cognitive decline</td>
<td>Exercise shifts microglia toward a neuroprotective phenotype</td>
</tr>
<tr>
<td>6</td>
<td>Insulin signaling / brain glucose utilization</td>
<td>↑ insulin sensitivity</td>
<td>Secondary</td>
<td>Improved neuronal fuel utilization</td>
<td>Supports memory and executive function</td>
<td>“Type 3 diabetes” concept in AD makes this pathway central</td>
</tr>
<tr>
<td>7</td>
<td>Amyloid-β production & clearance</td>
<td>↓ Aβ burden (modest)</td>
<td>Secondary</td>
<td>Reduced proteotoxic stress</td>
<td>Slows pathological cascade rather than reversing plaques</td>
<td>Exercise improves clearance more than production suppression</td>
</tr>
<tr>
<td>8</td>
<td>Tau phosphorylation / aggregation</td>
<td>↓ tau pathology (indirect)</td>
<td>Secondary</td>
<td>Axonal stability preservation</td>
<td>Supports memory retention and neuronal transport</td>
<td>Effect mediated via inflammation and insulin signaling</td>
</tr>
<tr>
<td>9</td>
<td>Oxidative stress / ROS</td>
<td>↓ chronic ROS</td>
<td>Adaptive</td>
<td>Redox stabilization</td>
<td>Protects synapses and mitochondria</td>
<td>Transient exercise ROS induces long-term antioxidant adaptation</td>
</tr>
<tr>
<td>10</td>
<td>Cognitive performance (memory, executive function)</td>
<td>↑ performance</td>
<td>Phenotypic</td>
<td>Functional outcome</td>
<td>Improved memory, attention, processing speed</td>
<td>Emergent result of upstream neurotrophic, vascular, and metabolic effects</td>
</tr>
</table>