# Environmental Exposures — Bioenergetic Longevity Framework

This document provides detailed mechanistic analyses of harmful environmental exposures evaluated through the lens of the bioenergetic theory of aging (see PLAN.md, METABOLISM_AND_AGING.md). The central question for each exposure is: **how does it impair mitochondrial energy production, disrupt hormonal signalling, or accelerate aging — and how can exposure be minimised?**

These are things to *avoid* or *minimise* — environmental chemicals, radiation, and other exposures that work against the bioenergetic framework. For beneficial therapeutic interventions, see THERAPIES.md. For supplement analyses, see SUPPLEMENTS.md.

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## Approach

Unlike SUPPLEMENTS.md and THERAPIES.md, this document does not use a tier system. Instead, each exposure is analysed by:

1. **What it is** — Chemical identity, sources, routes of exposure
2. **Mechanism of harm** — Molecular targets, pathway disruption, mitochondrial effects
3. **Evidence of harm** — Epidemiological and mechanistic evidence, dose-response where known
4. **Genotype-specific vulnerability** — Which genotypes increase susceptibility
5. **Exposure assessment** — How to identify and quantify personal exposure
6. **Practical avoidance** — Concrete, actionable steps to reduce exposure
7. **Mitigation** — Supplements or therapies (cross-ref SUPPLEMENTS.md, THERAPIES.md) that may reduce harm from unavoidable exposure

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## Table of Contents

*(Sections to be added as deep dives are completed)*

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## Planned Topics

The following exposures are queued for deep-dive analysis:

### Endocrine Disruptors

- **Xenoestrogens — Overview** — Definition, mechanism (estrogen receptor alpha/beta binding, non-genomic signalling), dose-response controversies (non-monotonic dose-response curves), the "cocktail effect" of multiple low-dose exposures, relevance to testosterone, thyroid function, and metabolic health.

- **Bisphenol A (BPA) and Analogues (BPS, BPF, BPAF)** — Polycarbonate plastics, thermal receipt paper, can linings. ERalpha/ERbeta agonism, anti-androgenic effects, thyroid hormone disruption (TR antagonism), mitochondrial dysfunction (Complex I inhibition, ROS generation), epigenetic effects (DNA methylation changes, transgenerational). "BPA-free" products often contain equally harmful analogues. Practical avoidance: glass/stainless steel containers, avoiding canned food, handling receipts.

- **Phthalates (DEHP, DBP, BBP, DiNP, DiDP)** — Plasticisers in PVC, food packaging, personal care products, fragrances. Anti-androgenic (suppress fetal Leydig cell testosterone synthesis — "phthalate syndrome"), PPARgamma activation (obesogenic), thyroid disruption, mitochondrial membrane depolarisation. Anogenital distance as a biomarker of prenatal exposure. Practical avoidance: fragrance-free products, avoiding plastic food containers, reading labels.

- **Parabens (Methylparaben, Ethylparaben, Propylparaben, Butylparaben)** — Preservatives in cosmetics, personal care products, some foods. Weak ERalpha agonism (butylparaben is most potent), anti-androgenic at high concentrations, detected in breast tumour tissue (Darbre 2004 — controversial). Practical avoidance: paraben-free personal care products.

- **Atrazine** — Herbicide (one of the most widely used globally). Aromatase induction (CYP19A1 upregulation) leading to increased estrogen synthesis, amphibian feminisation (Hayes et al. 2002, *PNAS*), endocrine disruption at environmentally relevant concentrations. Water contamination in agricultural regions. Practical avoidance: water filtration.

### Persistent Organic Pollutants

- **PFAS ("Forever Chemicals")** — PFOA, PFOS, GenX, and thousands of related compounds. Immune suppression (reduced vaccine response), thyroid disruption, liver toxicity, cholesterol elevation, cancer (kidney, testicular). Extreme environmental persistence (C-F bond). Sources: non-stick cookware, waterproof clothing, food packaging, contaminated water. Practical avoidance: cast iron/stainless steel cookware, water filtration (activated carbon + reverse osmosis).

- **Dioxins and PCBs** — AhR (aryl hydrocarbon receptor) activation, CYP1A1/CYP1B1 induction, immune suppression, endocrine disruption, carcinogenicity. Bioaccumulation in animal fat. Exposure primarily through diet (fatty fish, dairy, meat). CYP1A2 *1/*1F genotype relevance for AhR-mediated metabolism.

### Heavy Metals

- **Lead (Pb)** — Mitochondrial Complex I/III inhibition, delta-aminolevulinic acid dehydratase (ALAD) inhibition (heme synthesis disruption), calcium channel mimicry, endocrine disruption (testosterone suppression), neurotoxicity, bone storage (half-life ~20-30 years). Sources: old paint, contaminated water/soil, some supplements (turmeric adulteration — cross-ref SUPPLEMENTS.md Section 3.10), shooting ranges. Chelation vs avoidance.

- **Mercury (Hg)** — Methylmercury (organic, fish-borne) vs elemental mercury (dental amalgams) vs ethylmercury (thimerosal). Selenoprotein inhibition (mercury binds selenium with extreme affinity, depleting the Se pool needed for GPx/TrxR/DIO — cross-ref SUPPLEMENTS.md Section 1.4), mitochondrial dysfunction, neurodegeneration. The selenium-mercury molar ratio concept. Fish selection (high Se:Hg ratio fish are protective).

- **Cadmium (Cd)** — Tobacco smoke (primary source for smokers), contaminated food (rice, leafy greens, offal), occupational exposure. Mitochondrial dysfunction, nephrotoxicity, osteotoxicity, carcinogenicity (lung, kidney). Metallothionein induction and zinc competition. Extremely long biological half-life (~10-30 years in kidney).

- **Arsenic (As)** — Contaminated groundwater (Bangladesh, parts of India, some US regions), rice (bioaccumulates arsenite). Pyruvate dehydrogenase inhibition (arsenite binds dihydrolipoamide — directly impairs mitochondrial energy production), skin/bladder/lung cancer, cardiovascular disease. Inorganic vs organic arsenic. Practical avoidance: water testing, rice sourcing.

### Radiation and Electromagnetic

- **Blue Light at Night** — Melanopsin (OPN4) activation in intrinsically photosensitive retinal ganglion cells (ipRGCs), suppression of pineal melatonin synthesis via SCN-PVN-SCG pathway, circadian rhythm disruption, metabolic consequences (insulin sensitivity, cortisol timing). Practical avoidance: blue-light blocking glasses, screen filters, dimming lights after sunset.

- **Non-Ionising EMF (Radiofrequency/Microwave)** — Honest assessment needed. Mechanistic plausibility for voltage-gated calcium channel (VGCC) activation (Pall 2013 hypothesis) exists but remains controversial. IARC Group 2B classification (possibly carcinogenic). Large epidemiological studies (INTERPHONE, Million Women Study, Danish Cohort) show inconsistent results. This section should honestly separate established physics from speculative claims.

### Air Quality

- **Indoor Air Pollution** — VOCs (formaldehyde, benzene from furniture/paint), particulate matter from cooking (especially gas stoves — NO2), mould/mycotoxins. Mitochondrial effects of chronic low-level VOC exposure. Practical avoidance: HEPA filtration, ventilation, material selection.

- **Outdoor Air Pollution (PM2.5, PM10, O3, NO2)** — Systemic inflammation, cardiovascular disease, neurodegeneration (PM2.5 crosses BBB), mitochondrial dysfunction in alveolar epithelium, epigenetic aging acceleration. Geographic considerations.

### Food-Related Exposures

- **Seed Oils / PUFA Oxidation Products** — While partially covered in DIET.md, a dedicated deep dive on lipid peroxidation products (4-HNE, MDA, acrolein), their formation during cooking, cardiolipin damage, mitochondrial membrane effects, and the mechanistic basis for the anti-PUFA position of this framework.

- **Glyphosate** — Shikimate pathway disruption in gut microbiome (bacteria have this pathway; humans do not), potential effects on gut barrier integrity, chelation of minerals (Mn, Co, Zn), CYP enzyme inhibition (Samsel & Seneff hypothesis — controversial). Honest assessment: the Seralini affair and credibility problems in the anti-glyphosate literature vs legitimate mechanistic concerns.

- **Acrylamide** — Formed during high-temperature cooking (Maillard reaction) of starchy foods. Neurotoxicity, probable carcinogen (IARC 2A). Mitochondrial effects. Practical avoidance: cooking temperature management.

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*Each section will follow the standard deep-dive format established in SUPPLEMENTS.md: exhaustive mechanistic detail, researcher names with years and journals, ASCII pathway diagrams, evidence-level flagging, genotype-specific vulnerability (cross-referencing genotype-specific vulnerabilities), practical avoidance protocols, evidence summary tables, and key references.*

*Cross-references: SUPPLEMENTS.md (supplements that mitigate exposure harm), THERAPIES.md (therapies that support detoxification), METABOLISM_AND_AGING.md (bioenergetic framework), genotype-specific analysis (genotype-specific vulnerabilities), DIET.md (food-related exposures and dietary strategies)*
