04 — Longevity & Environment
Silo Scope
Targeting the cellular hallmarks of aging, biophysical inputs (light, heat, cold), and environmental toxin reduction.
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4.1 Cellular Health, NAD+ & Hallmarks of Aging
Interventions targeting genomic instability, mitochondrial dysfunction, senescence, and proteostasis.
- NAD+ Salvage Pathway (NMN, NR, CD38 Inhibition) — NAMPT rate-limiting enzyme, NMN vs. NR, Apigenin/Quercetin CD38 inhibition, PARP1 competition, methylation sinks (TMG pairing)
- Cellular Senescence & Senolytics (Fisetin, Quercetin, Dasatinib) — SASP suppression (senomorphics) vs. hit-and-run apoptosis of senescent cells (senolytics)
- Autophagy & Mitophagy (Spermidine, Urolithin A) — ULK1/AMPK signaling, PINK1/Parkin mitophagy, lysosomal biogenesis (TFEB), trehalose
- Mitochondrial Biogenesis & Uncoupling — PGC-1 activation, cardiolipin integrity, mild mitochondrial uncoupling
- Glycation & AGEs Inhibition (Carnosine, Benfotiamine) — Advanced Glycation End-products cross-linking, RAGE receptor blockade, transketolase activation
4.2 Photobiomodulation & Light Environment
Non-visual and mitochondrial photon signaling.
- Red & Near-Infrared Light Therapy (660nm, 850nm) — Cytochrome c oxidase (Complex IV) nitric oxide photodissociation, biphasic dose response (Arndt-Schulz curve, J/cm²), transcranial NIR (810nm/1064nm)
- Circadian Lighting & Melanopic Lux — High-CS (Circadian Stimulus) morning light (>1,000 melanopic EDI), zero-blue evening environments (<10 lux at eye level)
- UV Exposure, Nitric Oxide & Photobiology — UVA-induced dermal nitric oxide release (vasodilation), UVB vitamin D synthesis, POMC cleavage (-MSH, -endorphin)
- Blue Light Mitigation & Retinal Health — 400–500nm spectral filtering, macular carotenoids (lutein, zeaxanthin, astaxanthin), morning 670nm retinal exposure
4.3 Thermal Hormesis (Heat & Cold)
Hormetic temperature stress for cardiovascular, neurochemical, and metabolic adaptation.
- Sauna Protocols & Heat Shock Proteins — Dry/Finnish (80–100°C) vs. Infrared, HSP70/HSP90 upregulation, dynorphin/mu-opioid sensitization, plasma volume expansion, electrolyte replacement
- Cold Plunge, Norepinephrine & Brown Adipose Tissue — 250–500% norepinephrine & dopamine elevation, UCP1 uncoupling in BAT, cold shock proteins (RBM3), timing relative to hypertrophy (blunting mTOR if immediate post-lifting)
- Contrast Therapy & Vascular Conditioning — Alternating vasodilation/vasoconstriction, Sorenberg protocol (57 min sauna + 11 min cold/week), endothelial nitric oxide synthase (eNOS)
4.4 Environment & Toxin Mitigation
Minimizing exogenous xenobiotic load and optimizing endogenous clearance.
- Water Filtration, Remineralization & Hydrogen — Reverse osmosis + trace mineral restoration, molecular hydrogen () selective hydroxyl radical scavenging, disinfection byproducts (THMs)
- Indoor Air Quality (PM2.5, CO2, VOCs, HEPA) — True HEPA (H13/H14) + activated carbon, keeping bedroom for cognitive/sleep quality, radon & mold mycotoxin testing
- Heavy Metals, Microplastics & Endocrine Disruptors (PFAS, BPA) — Phthalates, bisphenols, PFOS/PFOA clearance (plasma/blood donation, soluble fiber bile sequestration), cookware & food storage swaps
- Detoxification Pathways (Phase I-III, Glutathione, Binders) — Cytochrome P450 (Phase I), Conjugation: glucuronidation/sulfation/methylation/glutathione (Phase II — sulforaphane/NRF2, calcium D-glucarate, NAC/GlyNAC), antiporter/bile/renal excretion (Phase III — TUDCA, activated charcoal/zeolite/pectin)