Terms and Abbreviations used in How To Live Forever
ALCAR — Acetyl-L-Carnitine. An amino acid derivative that shuttles fatty acids across the mitochondrial membrane for energy production. Supports mitochondrial function and cognitive health.
AMPK — AMP-activated protein kinase. The master energy-sensing enzyme that triggers cellular housecleaning (autophagy) and suppresses mTOR when energy is scarce. Activated by caloric restriction, fasting, exercise, and compounds including Gynostemma pentaphyllum, hesperidin, berberine, and EGCG. Declines with age.
AChE — Acetylcholinesterase. The enzyme that breaks down acetylcholine, the primary neurotransmitter for memory and cognition. AChE inhibition increases acetylcholine availability. Relevant to the sleep and dreaming protocol.
Apoptosis — Programmed cell death. The orderly self-destruction of damaged or dysfunctional cells that prevents them from persisting and causing harm. One of the three stages of the genomic integrity system. When apoptosis fails, senescent cells accumulate.
Autophagy — Literally “self-eating.” The cellular housecleaning process that removes damaged proteins, organelles, and metabolic debris. Activated by AMPK and suppressed by mTOR. Declines with age.
BRCA1/BRCA2 — Breast Cancer genes 1 and 2. DNA repair proteins responsible for double-strand break repair. Their expression is upregulated by I3C/DIM from cruciferous vegetables and suppressed by the DREAM complex.
CR — Caloric Restriction. Reducing caloric intake below ad libitum levels without malnutrition. The most validated single longevity intervention across species. Activates AMPK, suppresses mTOR, upregulates autophagy.
DHA — Docosahexaenoic acid. The primary omega-3 fatty acid in neural tissue. Essential for brain function, membrane integrity, and anti-inflammatory signaling. Found in fatty fish, especially sardines.
DIM — Diindolylmethane. The active gut metabolite of I3C (indole-3-carbinol) from cruciferous vegetables. Upregulates BRCA1 and BRCA2 DNA repair proteins.
DREAM complex — Dimerization partner, RB-like, E2F, and Multi-vulval class B protein complex. A gene suppressor that actively limits DNA repair gene expression in somatic cells, preventing them from using the full repair capacity their genome contains. EGCG disrupts DREAM assembly through DYRK1A inhibition.
DYRK1A — Dual-specificity tyrosine phosphorylation-regulated kinase 1A. The kinase that assembles the DREAM complex by phosphorylating LIN52. Inhibited by EGCG, apigenin, harmine, and flavokavain A — thereby releasing DREAM suppression of DNA repair genes.
EGCG — Epigallocatechin gallate. The primary active polyphenol in green tea. Antiviral, anti-inflammatory, SIRT1-activating, and a DYRK1A inhibitor that disrupts DREAM complex assembly to release suppressed DNA repair gene expression.
EPA — Eicosapentaenoic acid. An omega-3 fatty acid with primarily anti-inflammatory effects. Found alongside DHA in fatty fish.
GH — Growth hormone. Secreted primarily during deep sleep in a pulsatile pattern. Declines with age. Essential for muscle repair, fat metabolism, and cellular regeneration overnight.
Hallmarks of Aging — The twelve biological processes whose accumulation produces aging, established by López-Otín et al. and updated in 2023: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, dysbiosis, and disabled macroautophagy.
HPA axis — Hypothalamic-pituitary-adrenal axis. The stress response system that regulates cortisol secretion. Chronic activation produces the cortisol dysregulation associated with sleep disruption, immune suppression, and accelerated aging.
HIIT — High-Intensity Interval Training. Exercise protocol alternating intense effort with recovery periods. The most potent available stimulus for mitochondrial biogenesis and cardiovascular adaptation.
I3C — Indole-3-carbinol. A compound from cruciferous vegetables that converts to DIM in the gut, upregulating BRCA1 and BRCA2 DNA repair proteins. Found in broccoli, cauliflower, cabbage, and kale.
IGF-1 — Insulin-like growth factor 1. A growth-promoting hormone that parallels GH activity. Elevated IGF-1 is associated with both muscle maintenance and increased cancer risk — context-dependent effects.
ITP — Interventions Testing Program. The National Institute on Aging’s program for testing potential longevity compounds in genetically heterogeneous mice at three independent sites simultaneously. The most rigorous standard for mammalian lifespan extension evidence.
K2 — Vitamin K2 (menaquinone). Directs calcium into bones and away from arterial walls. Found in fermented foods, particularly natto (fermented soybeans). Distinct from K1 (phylloquinone) found in leafy greens.
LEF — Life Extension Foundation. The supplement company and research organization founded by William Falloon in 1980. Publisher of Life Extension Magazine and funder of longevity research.
LPS — Lipopolysaccharide. A bacterial endotoxin used in challenge studies to produce a standardized inflammatory response, testing immune function without requiring live pathogen exposure.
mTOR — Mechanistic target of rapamycin. The cellular growth-promoting complex that suppresses autophagy and cellular repair when nutrients are abundant. Suppressed by AMPK. Dysregulation contributes to cancer, metabolic disease, and aging. The drug rapamycin inhibits it directly.
NAD+ — Nicotinamide adenine dinucleotide. A coenzyme essential for cellular energy production and the substrate for PARP (DNA repair) and sirtuin (longevity) enzymes. Declines with age. Restored by niacin, NR, and NMN supplementation.
NER — Nucleotide excision repair. The DNA repair pathway that removes bulky lesions including UV-induced thymine dimers and transcription-blocking adducts. Enhanced by Cat’s Claw (Uncaria tomentosa).
NHEJ — Non-homologous end joining. One of the four major DNA double-strand break repair pathways. Rejoins broken DNA ends without requiring a homologous template — faster but less precise than homologous recombination. Released from DREAM complex suppression by EGCG through DYRK1A inhibition.
BER — Base excision repair. The DNA repair pathway that removes small, non-helix-distorting base lesions such as oxidized bases and deaminated bases. The highest-volume repair pathway, addressing the spontaneous chemical instability of DNA in aqueous solution.
HR — Homologous recombination. The high-fidelity DNA double-strand break repair pathway using a homologous template to accurately restore the original sequence. The pathway in which BRCA1 and BRCA2 play their primary roles.
NK cells — Natural killer cells. Innate immune lymphocytes that detect and destroy cancer cells and virally infected cells without prior sensitization. Decline in number and activity with age. Maintained by echinacea supplementation.
NMN — Nicotinamide mononucleotide. A direct NAD+ precursor with documented lifespan extension in animal models and emerging human biomarker data.
NR — Nicotinamide riboside. A NAD+ precursor with human clinical data supporting NAD+ restoration.
NRF2 — Nuclear factor erythroid 2-related factor 2. The master regulator of antioxidant and detoxification gene expression. Activated by sulforaphane (from cruciferous vegetables), curcumin, and other compounds in the protocol.
PARP — Poly(ADP-ribose) polymerase. The primary DNA damage detection and repair signaling enzyme. Requires NAD+ as substrate. Declining NAD+ with age impairs PARP function and reduces DNA repair capacity.
PFAS — Per- and poly-fluoroalkyl substances are man-made “forever chemicals” used since the 1940sl
PQQ — Pyrroloquinoline quinone. A micronutrient that directly stimulates mitochondrial biogenesis through PGC-1α activation. C. elegans lifespan extension of 30-33%. Mouse lifespan extension of 12.7% in 2026 SAMP8 study. Highest food source: fermented soybeans (natto).
RCT — Randomized controlled trial. The gold standard for human clinical evidence — participants randomly assigned to treatment or placebo, with outcomes compared.
ROS — Reactive oxygen species. Free radicals and other oxidizing molecules produced as byproducts of cellular metabolism. Primary source of oxidative DNA damage. Addressed by the antioxidant architecture throughout the protocol.
SAC — S-allylcysteine. The primary water-soluble active compound in aged garlic extract. Cardiovascular protection through hydrogen sulfide enhancement, antioxidant, and anti-inflammatory mechanisms.
SASP — Senescence-associated secretory phenotype. The inflammatory cytokine cloud produced by senescent cells that refuse to die. Drives the chronic low-grade inflammation of aging. Targeted by senolytics and quercetin.
SIRT1/SIRT6 — Sirtuin 1 and Sirtuin 6. NAD+-dependent deacetylase enzymes with documented roles in longevity, DNA repair, metabolic regulation, and epigenetic maintenance. Activated by resveratrol, pterostilbene, and NAD+ precursors.
TNF-α — Tumor necrosis factor alpha. A primary pro-inflammatory cytokine. Elevated chronically in metabolic syndrome, obesity, and aging. Reduced by echinacea, EGCG, omega-3 fatty acids, and quercetin.
WBTB — Wake-back-to-bed. A lucid dreaming technique involving waking after 4-6 hours of sleep, remaining awake briefly, then returning to sleep — timing the entry into REM sleep that produces vivid dreaming.
Organizations and Products
CALERIE — Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy. The major human caloric restriction trial that used the DunedinPACE epigenetic clock to demonstrate slowing of biological aging rate.
FLORASSIST — Life Extension’s probiotic product line. FLORASSIST Targeted Phage includes bacteriophages that selectively regulate gut bacterial populations as part of the holobiont ecosystem.
ITP — see above.
LEF — see above.
NHANES — National Health and Nutrition Examination Survey. Large US population health survey whose data provides much of the Category 1 epidemiological mortality evidence in Chapter 11.
NOVOSLabs — Longevity supplement company that collaborated with Newcastle University on the 12-ingredient nutraceutical study showing comparable effects to pharmaceutical senolytics.
TranslAGE — A harmonized database of 51 longitudinal human intervention studies with DNA methylation data, used to systematically compare longevity intervention effects across 16 epigenetic clocks. Published in Nature Medicine 2026.
Epigenetic Clock Terms
DunedinPACE — A DNA methylation-based biomarker measuring the rate of biological aging rather than current biological age. The most responsive clock to both lifestyle and pharmaceutical interventions in the TranslAGE analysis.
GrimAge — An epigenetic clock trained on time-to-death data. The strongest predictor of all-cause mortality among the major epigenetic clocks.
PhenoAge — An epigenetic clock specifically designed to predict phenotypic aging outcomes including all-cause mortality, cancer, and Alzheimer’s disease. Used in the DO-HEALTH trial.
SystemsAge — An explainable epigenetic clock providing aging scores for 11 distinct physiological systems simultaneously, allowing organ-system-specific assessment of intervention effects.
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