The Longevity Glossary

A toxic metabolite of alcohol metabolism; a Group 1 carcinogen that forms DNA adducts and impairs DNA repair. Central to alcohol's cancer risk. Read: Alcohol and Longevity →

An anti-inflammatory hormone secreted by adipose tissue. Higher levels are associated with insulin sensitivity and reduced cardiovascular risk. Paradoxically, levels decrease as body fat increases. Read: Visceral Fat →

A keystone gut bacterium that maintains the intestinal mucus layer. Associated with metabolic health, insulin sensitivity, and reduced inflammation. Declines with age and Western diets. Read: Gut Microbiome Optimization →

A Krebs cycle intermediate that declines with age. Supplementation extended lifespan in mice and improved frailty markers. Human evidence is limited to small trials showing biological age reduction. Read: Supplements Guide →

A cellular energy sensor activated by low-energy states, exercise, fasting, and certain drugs (metformin, berberine). Promotes autophagy, mitochondrial biogenesis, and fat oxidation. One of the key nutrient-sensing pathways in longevity biology. Read: AMPK →

A peptide that accumulates as plaques in Alzheimer's disease. Cleared during deep sleep via the glymphatic system. The amyloid hypothesis remains debated, but reducing accumulation through sleep, exercise, and vascular health is evidence-supported. Read: Alzheimer's Prevention →

The age-related decline in the muscle's ability to synthesize protein in response to amino acids and resistance training. Requires higher protein doses per meal (40-50g) to achieve the same muscle protein synthesis response as younger individuals. Read: Muscle Protein Synthesis →

A protein present on every atherogenic lipoprotein particle (LDL, VLDL, IDL, Lp(a)). The single best blood biomarker for cardiovascular risk assessment. Superior to LDL-C because it counts particles rather than cholesterol content. Read: ApoB →

A gene with three major variants (ε2, ε3, ε4). APOE4 carriers have 3-12x increased Alzheimer's risk. APOE2 is associated with exceptional longevity. The most actionable longevity-related gene variant for most people. Read: Longevity Genomics →

Progressive buildup of lipid-laden plaques in arterial walls driven by ApoB-containing lipoprotein particles. The pathological process underlying heart attacks and strokes. Begins decades before clinical events. Read: ApoB →

A cellular recycling process that degrades damaged organelles, misfolded proteins, and intracellular pathogens. Activated by fasting, exercise, rapamycin, and AMPK signaling. One of the 12 hallmarks of aging. Declines with age. Read: Autophagy →

A growth factor critical for neuroplasticity, memory formation, and neuronal survival. Activated powerfully by aerobic exercise, adequate sleep, and certain dietary factors. Reduced levels are associated with depression and cognitive decline. Read: BDNF →

A plant alkaloid that activates AMPK, lowers blood glucose, reduces LDL cholesterol, and modulates the gut microbiome. Often called 'nature's metformin' due to overlapping mechanisms, though the evidence base is smaller. Read: Berberine →

The metabolic process of breaking down fatty acids for energy in mitochondria. Enhanced by glucagon signaling, exercise, and fasting. Central to metabolic flexibility and the mechanism behind retatrutide's liver fat reduction. Read: GLP-1 Agonists →

The proportion of a substance that enters systemic circulation when introduced into the body. Critical for supplement selection — e.g., ubiquinol vs ubiquinone, methylfolate vs folic acid, magnesium glycinate vs oxide. Read: Brand Testing →

An estimate of how old your body is functionally, independent of chronological age. Measured via epigenetic clocks (DNA methylation), blood biomarker algorithms, or composite assessments. Can differ significantly from chronological age based on lifestyle. Read: Biological Age Testing →

Five geographic regions (Okinawa, Sardinia, Nicoya, Ikaria, Loma Linda) where populations live measurably longer. Common factors include plant-forward diets, daily movement, social integration, purpose, and moderate caloric intake. Read: Blue Zones →

Metabolically active fat tissue that generates heat through uncoupled respiration. Activated by cold exposure. Associated with improved glucose metabolism and reduced obesity risk. Read: Cold Exposure →

A short-chain fatty acid produced by gut bacteria fermenting dietary fiber. The primary energy source for colonocytes, strengthens the intestinal barrier, reduces inflammation, and activates regulatory T cells. The longevity-relevant fatty acid. Read: Gut Microbiome and Longevity →

A CT-based measurement of calcified plaque in the coronary arteries. A score of zero indicates very low 10-year cardiovascular risk. Considered the single best test for asymptomatic cardiovascular risk assessment. Read: CAC Scoring →

Reducing calorie intake by 10-25% below ad libitum levels without malnutrition. The most consistently demonstrated lifespan-extending intervention in animal models. The CALERIE trial showed metabolic benefits in humans at ~12% restriction. Read: Caloric Restriction →

The permanent arrest of cell division. Senescent cells accumulate with age and secrete inflammatory factors (the SASP) that damage neighboring tissue. Targeted removal by senolytic drugs is a major area of longevity research. Read: Cellular Senescence →

A concept popularized by Peter Attia: identifying the 10 physical tasks you want to perform in the last decade of life (e.g., carrying groceries, playing with grandchildren, climbing stairs) and training for them now. Read: Peter Attia's Medicine 3.0 →

A wearable device that measures interstitial glucose every 5-15 minutes. Reveals postprandial glucose spikes, overnight patterns, and individual food responses that a single fasting glucose measurement misses. Read: CGM for Non-Diabetics →

The number of years since birth. Distinct from biological age. Two 50-year-olds may have biological ages of 42 and 58 based on epigenetic and metabolic markers. Read: Biological Age Testing →

The ~24-hour internal biological clock governed by the suprachiasmatic nucleus (SCN). Regulates sleep-wake cycles, hormone secretion, metabolism, and gene expression. Disruption accelerates aging across multiple systems. Read: Circadian Rhythm and Longevity →

An essential electron carrier in the mitochondrial electron transport chain. Levels decline with age and are depleted by statin drugs. Ubiquinol is the reduced (active) form with superior bioavailability. Read: CoQ10 and Ubiquinol →

The primary stress hormone produced by the adrenal cortex. Chronically elevated cortisol accelerates aging by suppressing immune function, promoting visceral fat, impairing sleep, and increasing inflammation. Read: Chronic Stress →

An amino acid derivative that serves as a phosphate buffer for ATP regeneration. The most evidence-backed supplement for muscle strength, with emerging evidence for cognitive benefits. Chronic supplementation of 3-5g/day is well-supported. Read: Creatine →

Small signaling proteins that regulate inflammation and immune responses. Pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) are elevated in inflammaging. Anti-inflammatory cytokines (IL-10) counterbalance them. Read: Inflammaging →

The most-studied senolytic combination. Dasatinib (a cancer drug) and quercetin (a flavonoid) selectively induce apoptosis in senescent cells. Human trials are ongoing for idiopathic pulmonary fibrosis and diabetic kidney disease. Read: Longevity Science 2025 →

A body composition imaging technique that measures bone density, lean mass, visceral fat, and fat distribution with high precision. The clinical standard for sarcopenia and osteoporosis assessment. Read: Bone Density →

A marine omega-3 fatty acid that comprises ~40% of brain phospholipids. Critical for neuronal membrane integrity, synaptic plasticity, and neuroprotection. Found in fatty fish and algal oil. Read: Omega-3 →

The addition of methyl groups to cytosine bases in DNA, which regulates gene expression without changing the DNA sequence. The basis of epigenetic clocks that measure biological age. Read: Epigenetic Clocks →

An enzyme that rapidly degrades native GLP-1 and GIP hormones within minutes. GLP-1 receptor agonists like semaglutide are engineered to resist DPP-4 degradation, enabling once-weekly dosing. Read: GLP-1 Agonists →

A third-generation epigenetic clock developed by researchers at Duke and Columbia universities. Unlike earlier clocks that estimate biological age, DunedinPACE measures the current rate (pace) of aging. Considered the most actionable epigenetic measure for tracking intervention effects. Read: Epigenetic Clocks →

An imbalance in the gut microbiome characterized by reduced diversity, decreased beneficial species, and overgrowth of pathogenic organisms. One of the 12 hallmarks of aging. Read: Gut Microbiome →

A calculated measure of kidney function based on creatinine levels, age, sex, and race. Values below 60 mL/min indicate chronic kidney disease. A powerful predictor of cardiovascular mortality. Read: Kidney Health →

The health and responsiveness of the endothelium — the single-cell layer lining all blood vessels. Endothelial dysfunction is the earliest detectable stage of atherosclerosis, preceding plaque formation by decades. Read: Advanced CV Testing →

A marine omega-3 fatty acid with potent anti-inflammatory properties. More cardiovascular-specific than DHA. Found in fatty fish and algal oil. Combined with DHA, forms the basis of the Omega-3 Index. Read: Omega-3 →

An algorithm that uses DNA methylation patterns to estimate biological age or pace of aging. Major clocks include Horvath (pan-tissue), PhenoAge (disease risk), GrimAge (mortality), and DunedinPACE (pace of aging). Read: Epigenetic Clocks →

The level of insulin in the blood after an overnight fast. Elevated fasting insulin indicates insulin resistance — often decades before HbA1c or fasting glucose become abnormal. Optimal longevity range: 2-6 μIU/mL. Read: Fasting Insulin →

A 5-day calorie-restricted protocol (800-1100 kcal/day) designed to provide food while triggering fasting-like metabolic changes including autophagy, stem cell regeneration, and reduced IGF-1. Developed by Valter Longo's lab. Read: Prolonged Fasting and FMD →

A blood protein that stores iron. Optimal longevity range: 40-100 ng/mL for men, 30-80 for women. Elevated ferritin indicates iron overload, which accelerates oxidative damage. Low ferritin indicates iron deficiency. Read: Iron Status →

Indigestible carbohydrates fermented by gut bacteria into short-chain fatty acids (butyrate, propionate, acetate). The primary dietary driver of microbiome diversity. Target: 30-40g/day from whole food sources. Read: Gut Optimization →

The most consistently replicated human longevity gene. FOXO3 encodes a transcription factor that activates DNA repair, antioxidant defense, autophagy, and stress resistance. Beneficial variants are enriched in centenarian populations. Read: Longevity Genomics →

Reactive oxygen species produced as byproducts of mitochondrial respiration. At low levels, ROS serve as signaling molecules. Excessive ROS cause oxidative damage to DNA, proteins, and lipids. The mitochondrial theory of aging centers on ROS accumulation. Read: Mitochondria →

The accumulation of DNA damage over time from endogenous (replication errors, ROS) and exogenous (UV, pollution) sources. The first hallmark of aging. Partially addressed by DNA repair enzymes (PARPs), which require NAD+. Read: Hallmarks of Aging →

A drug or intervention that targets the biological mechanisms of aging itself, rather than treating individual age-related diseases. No gerotherapeutic has received FDA approval. GLP-1 agonists and rapamycin are leading candidates. Read: Longevity Science 2025 →

An incretin hormone that enhances insulin secretion, promotes lipid metabolism, and has direct effects on adipose tissue and bone. Targeted by tirzepatide and retatrutide alongside GLP-1. Read: GLP-1 Agonists →

A gut hormone released after eating that stimulates insulin, suppresses glucagon, slows gastric emptying, and reduces appetite via brain signaling. Synthetic GLP-1 receptor agonists (semaglutide, tirzepatide, retatrutide) are the most-discussed longevity drug class of 2025-2026. Read: GLP-1 Agonists →

The magnitude of blood glucose fluctuations over a day. High glycemic variability (large spikes and crashes) is associated with oxidative stress, endothelial damage, and accelerated aging — even when average glucose is normal. Read: CGM →

The brain's waste clearance system, active primarily during deep sleep. Removes amyloid-beta, tau proteins, and metabolic waste via cerebrospinal fluid flow through perivascular channels. Impaired glymphatic function is implicated in Alzheimer's disease. Read: Brain Longevity Blueprint →

A second-generation epigenetic clock designed to predict time to death. Uses DNA methylation surrogates for smoking, plasma proteins, and other factors. The best epigenetic clock for mortality prediction as of 2025. Read: Epigenetic Clocks →

Maximal force produced by hand grip. A validated predictor of all-cause mortality that correlates with overall muscle mass, functional capacity, and cardiovascular health. Below-average grip strength is associated with accelerated aging. Read: Grip Strength →

A pituitary hormone that peaks during slow-wave sleep. Declines ~14% per decade after age 30 (somatopause). GH replacement remains controversial for longevity — increased IGF-1 may accelerate aging despite short-term benefits. Read: Hormones →

The bidirectional communication network between the gastrointestinal tract and the central nervous system, mediated by the vagus nerve, immune signaling, neurotransmitter production, and microbial metabolites. Read: Gut-Brain Axis →

The 12 interconnected biological processes identified as the fundamental drivers of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled autophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, inflammaging, and dysbiosis. Read: Hallmarks of Aging →

An autoimmune condition where the immune system attacks the thyroid gland. The most common cause of hypothyroidism. Detected via anti-TPO and anti-thyroglobulin antibodies. Read: Thyroid Function →

A measure of average blood glucose over the preceding 2-3 months. Standard diagnostic for diabetes (≥6.5%). Longevity-optimal range: 4.8-5.3%. Read: Bloodwork Guide →

The period of life spent in good health, free from chronic disease, disability, and significant functional decline. Distinct from lifespan (total years alive). The primary goal of longevity medicine.

The master regulator of iron metabolism. Produced by the liver. Elevated hepcidin blocks iron absorption and traps iron in cells; low hepcidin permits excessive iron absorption. Read: Iron Status →

Exercise protocol alternating short bursts of high-intensity effort (85-95% max heart rate) with recovery periods. The Norwegian 4x4 protocol is the most studied HIIT format for VO2 max improvement. Read: HIIT vs Steady-State →

The birth of new neurons in the hippocampus (the brain's memory center). One of the few brain regions where adult neurogenesis occurs. Driven by aerobic exercise, BDNF, sleep, and enriched environments. Read: Exercise and the Brain →

A calculated ratio of fasting insulin × fasting glucose / 405 that estimates insulin resistance. Optimal: below 1.0. Values above 2.0 suggest clinically significant insulin resistance. Read: Fasting Insulin and HOMA-IR →

An amino acid intermediate in the methionine cycle. Elevated levels (>10 μmol/L) are associated with cardiovascular disease and cognitive decline. Lowered by folate (methylfolate), B12, and B6 supplementation. Read: Homocysteine →

A dose-response phenomenon where a low dose of a stressor (exercise, fasting, cold, heat, phytochemicals) produces beneficial adaptive responses, while higher doses are harmful. The biological basis of many longevity interventions.

The first pan-tissue epigenetic clock (2013). Uses 353 CpG sites to estimate biological age across virtually all tissue types. Accuracy: ±3.6 years. The original benchmark for epigenetic age measurement. Read: Epigenetic Clocks →

Replacement of declining sex hormones (estradiol, progesterone, testosterone) during aging. For women, the timing hypothesis suggests initiation within 10 years of menopause onset for cardiovascular benefit. Transdermal estradiol with micronized progesterone is the evidence-preferred formulation. Read: HRT for Women →

The variation in time intervals between successive heartbeats. Higher HRV indicates greater parasympathetic (rest-and-digest) tone and autonomic flexibility. A validated biomarker of stress resilience, fitness, and recovery capacity. Read: HRV →

A blood marker of systemic inflammation produced by the liver. Levels below 1.0 mg/L indicate low cardiovascular risk; above 3.0 indicates elevated risk. Used to assess inflammaging and track anti-inflammatory interventions. Read: Bloodwork Guide →

A growth factor regulated by growth hormone. Higher IGF-1 promotes muscle growth and tissue repair but may accelerate aging by activating mTOR. Centenarians typically have lower IGF-1 levels. The growth-longevity tradeoff. Read: Centenarian Biology →

The progressive deterioration of immune function with aging. Characterized by thymic involution, reduced naive T-cell production, increased senescent T-cells, and impaired vaccine responses. Zinc deficiency accelerates immunosenescence. Read: Zinc and Immune Aging →

A gut hormone that stimulates insulin secretion in a glucose-dependent manner after eating. The two major incretins are GLP-1 and GIP. Pharmaceutical analogs of these hormones form the GLP-1 agonist drug class. Read: GLP-1 Agonists →

Chronic, low-grade, sterile inflammation that increases with age. Driven by senescent cell accumulation (SASP), gut barrier dysfunction, visceral fat, and immune dysregulation. Considered a root cause of most age-related diseases. Read: Inflammaging →

A condition where cells become less responsive to insulin's signal, requiring progressively higher insulin levels to maintain glucose homeostasis. Precedes type 2 diabetes by 10-20 years. Detected early by fasting insulin and HOMA-IR. Read: Fasting Insulin →

Any eating pattern that cycles between periods of eating and fasting. Common formats include 16:8 (16 hours fasted, 8-hour eating window) and 5:2 (two days of very low calories per week). Benefits are primarily mediated through caloric reduction and circadian alignment. Read: Fasting Myths →

Fuel molecules produced by the liver during fasting or carbohydrate restriction. Beta-hydroxybutyrate (BHB) serves as both an energy substrate and a signaling molecule that activates HDAC inhibition, reduces inflammation, and may support brain function. Read: Ketogenic Diet →

The exercise intensity at which lactate begins to accumulate in the blood faster than it can be cleared. Zone 2 training operates just below the first lactate threshold (~2 mmol/L). Training at this intensity maximizes fat oxidation and mitochondrial adaptation. Read: Zone 2 Training →

A branched-chain amino acid that directly activates mTORC1 and muscle protein synthesis. The 'anabolic trigger' — approximately 2.5-3g per meal is required to maximally stimulate MPS. Found most abundantly in whey protein, eggs, and meat. Read: Muscle Protein Synthesis →

The total number of years an individual lives. Distinct from healthspan. The goal of longevity medicine is to extend both lifespan and healthspan, ideally compressing the period of decline (morbidity compression).

A genetically determined lipoprotein particle with both atherogenic and thrombotic properties. Levels are 90% determined by genetics and largely unresponsive to lifestyle. Elevated Lp(a) (>50 nmol/L) significantly increases cardiovascular risk. RNA-based therapies are in late-stage trials. Read: Lp(a) →

A composite clinical endpoint typically including cardiovascular death, nonfatal myocardial infarction (heart attack), and nonfatal stroke. The standard primary endpoint in cardiovascular outcome trials. Read: GLP-1 Agonists →

An essential mineral involved in 300+ enzymatic reactions including ATP production, DNA repair, nerve function, and muscle contraction. An estimated 50-60% of adults are deficient. Glycinate and threonate forms have superior bioavailability. Read: Magnesium →

Formerly called NAFLD. Accumulation of excess fat in the liver not caused by alcohol. Affects ~30% of adults globally. Progresses to MASH (steatohepatitis), fibrosis, and potentially cirrhosis. Strongly driven by fructose intake and insulin resistance. Read: Liver Health →

A conceptual framework popularized by Peter Attia describing a proactive, preventive approach to medicine — in contrast to Medicine 2.0's reactive disease treatment. Emphasizes early detection, aggressive risk factor management, and interventions targeting the four leading causes of death. Read: Peter Attia's Medicine 3.0 →

A dietary pattern emphasizing olive oil, vegetables, legumes, fruits, whole grains, fish, and moderate wine. The most evidence-supported dietary pattern for longevity, validated by the PREDIMED RCT showing 30% cardiovascular event reduction. Read: Mediterranean Diet →

A hormone produced by the pineal gland in response to darkness. Regulates circadian rhythm and sleep onset. Also functions as a powerful antioxidant and immunomodulator. Exogenous doses of 0.3-0.5 mg are physiological; common commercial doses (5-10 mg) are supraphysiological. Read: Melatonin →

A genetic epidemiology method that uses genetic variants as proxies for exposures to infer causality. More resistant to confounding than observational studies. Used to disprove the J-curve alcohol hypothesis and establish causal effects of Lp(a). Read: Alcohol and Longevity →

The ability to efficiently switch between glucose and fat oxidation depending on fuel availability and energy demand. Impaired metabolic flexibility is an early marker of insulin resistance and metabolic disease. Zone 2 training is the primary intervention. Read: Metabolic Flexibility →

A biguanide drug used for type 2 diabetes that activates AMPK, reduces hepatic glucose output, and has pleiotropic anti-aging effects. Being tested in the TAME (Targeting Aging with Metformin) trial — the first RCT designed to test a drug against aging itself. Read: Metformin →

The bioactive form of folate (vitamin B9). Unlike synthetic folic acid, methylfolate does not require MTHFR enzyme conversion and is preferred for individuals with MTHFR polymorphisms (affecting ~40% of the population). Read: Folate vs Folic Acid →

The variety of microbial species in the gut ecosystem. Higher diversity is consistently associated with better metabolic health, stronger immune function, and longer lifespan. Reduced by antibiotics, ultra-processed food, and stress. Read: Gut Microbiome →

A hybrid of the Mediterranean and DASH diets specifically designed for brain health. Emphasizes berries, leafy greens, nuts, olive oil, fish, and whole grains while limiting red meat, cheese, butter, pastries, and fried food. Read: Mediterranean Diet →

Double-membrane organelles that produce ATP via oxidative phosphorylation. Mitochondrial dysfunction — decreased ATP output, increased ROS production, impaired quality control — is one of the 12 hallmarks of aging. Zone 2 training is the most evidence-backed intervention for mitochondrial health. Read: Mitochondria and Aging →

The selective autophagy of damaged mitochondria. Essential for mitochondrial quality control. Activated by exercise, fasting, and urolithin A. Impaired mitophagy leads to accumulation of dysfunctional mitochondria that produce excess ROS. Read: Mitochondria and Aging →

Individuals with normal BMI but elevated visceral fat, insulin resistance, and inflammatory markers. Estimated 10-20% of normal-weight adults. DEXA scanning and fasting insulin testing detect this phenotype. Read: Visceral Fat →

The concept of delaying the onset of disease and disability to the latest possible point in life, compressing the period of decline into the shortest possible timeframe before death. The practical goal of healthspan extension.

An enzyme that converts folate to its active form (5-MTHF). Common polymorphisms (C677T, A1298C) reduce enzyme efficiency by 30-70%, leading to elevated homocysteine and impaired methylation. Affects approximately 40% of the global population. Read: Folate vs Folic Acid →

A master nutrient-sensing kinase that promotes growth, protein synthesis, and cell proliferation when activated. Chronic overactivation accelerates aging. Periodic inhibition (via fasting, rapamycin, or exercise-rest cycling) is a core longevity strategy. Read: mTOR →

The process of building new muscle protein in response to amino acids (especially leucine) and mechanical tension from resistance training. The rate of MPS determines whether muscle mass is maintained, gained, or lost. Read: Muscle Protein Synthesis →

Signaling molecules released by contracting skeletal muscle during exercise. Include IL-6, irisin, BDNF, and others. Mediate many of exercise's systemic benefits including anti-inflammatory effects, metabolic regulation, and neuroprotection. The basis of the 'muscle as endocrine organ' concept. Read: Strength Training →

A coenzyme essential for mitochondrial energy production, DNA repair (via PARPs), and sirtuin activation. NAD+ levels decline 40-50% between ages 40 and 70. NMN and NR are precursor supplements being studied to restore NAD+ levels. Read: NAD+ and Sirtuins →

The brain's ability to reorganize itself by forming new neural connections throughout life. Driven by BDNF, exercise, learning, and adequate sleep. Not limited to youth — adults retain meaningful plasticity, though the rate declines. Read: Neuroplasticity →

A direct precursor to NAD+ that bypasses the rate-limiting NAMPT step in the salvage pathway. Human trial data is emerging but limited compared to NR. Typical supplemental doses: 250-1000 mg/day. Read: NMN vs NR →

An NAD+ precursor that enters the salvage pathway via NRK enzymes. More human clinical trial data than NMN as of 2025. The CHROMAVIT trial showed modest NAD+ elevation. Typical supplemental doses: 300-1000 mg/day. Read: NMN vs NR →

Cellular pathways that detect nutrient availability and adjust growth and metabolism accordingly. The four major nutrient-sensing pathways in longevity biology are mTOR, AMPK, sirtuins, and insulin/IGF-1 signaling. Read: Hallmarks of Aging →

The percentage of EPA+DHA in red blood cell membranes. An Omega-3 Index above 8% is associated with the lowest cardiovascular and cognitive risk. Below 4% is considered high-risk. More clinically useful than measuring plasma omega-3 levels. Read: Omega-3 →

A sleep disorder where excessive monitoring of sleep data (from wearables) paradoxically increases sleep anxiety and worsens sleep quality. An iatrogenic effect of consumer sleep tracking. Read: Sleep Tracking →

DNA repair enzymes that consume NAD+ to fix single-strand DNA breaks. PARP activity increases with age as DNA damage accumulates, depleting the NAD+ pool and creating a vicious cycle of impaired repair and further damage. Read: NAD+ →

A second-generation epigenetic clock (2018) trained to predict disease risk rather than chronological age. Uses a combination of DNA methylation markers. Better at predicting morbidity and mortality than the original Horvath clock. Read: Epigenetic Clocks →

A diverse class of plant-derived compounds (flavonoids, stilbenes, phenolic acids) that activate stress-response pathways via hormesis rather than direct antioxidant activity. Key sources include berries, green tea, dark chocolate, olive oil, and red wine. Read: Polyphenols →

A landmark randomized controlled trial of 7,447 participants demonstrating that a Mediterranean diet supplemented with extra-virgin olive oil or mixed nuts reduced major cardiovascular events by approximately 30% compared to a low-fat control diet. Read: Mediterranean Diet →

The maintenance of proper protein folding, function, and degradation. Loss of proteostasis — the accumulation of misfolded or aggregated proteins — is one of the 12 hallmarks of aging and underlies neurodegenerative diseases. Read: Hallmarks of Aging →

An mTOR inhibitor originally used as an immunosuppressant in organ transplantation. Extended lifespan in every model organism tested (yeast, worms, flies, mice). Intermittent low-dose protocols are being studied in humans for longevity applications. Read: Rapamycin and mTOR →

The sleep stage characterized by rapid eye movements, vivid dreaming, near-total muscle atonia, and active brain metabolism. Essential for memory consolidation, emotional processing, and creativity. Comprises ~20-25% of total sleep. Suppressed by alcohol. Read: Sleep Stages →

A polyphenol found in red grapes and wine. Initially promoted as a sirtuin activator, but subsequent research showed the original findings were largely artifact. Current evidence does not support resveratrol supplementation for longevity in humans. Read: Sirtuins →

A triple receptor agonist (GLP-1/GIP/glucagon) in phase 3 clinical trials. Produced 24.2% weight loss at 48 weeks in phase 2 and 86% liver fat reduction. The glucagon component provides energy expenditure increases and hepatic fat oxidation unavailable from earlier drugs. Read: GLP-1 Agonists →

Age-related loss of skeletal muscle mass and function. Begins around age 30 and accelerates after 60. Strongly associated with increased mortality, falls, frailty, and metabolic decline. The primary countermeasure is resistance training combined with adequate protein. Read: Strength Training →

The cocktail of inflammatory cytokines, chemokines, proteases, and growth factors secreted by senescent cells. The SASP drives local and systemic inflammation, damages neighboring tissue, and promotes further senescence in a paracrine fashion. Read: Cellular Senescence →

A landmark cardiovascular outcome trial (17,604 participants) demonstrating that semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% in non-diabetic individuals with obesity. Published in NEJM 2023. Read: GLP-1 Agonists →

A GLP-1 receptor agonist marketed as Ozempic (diabetes) and Wegovy (weight management). The SELECT trial demonstrated 20% cardiovascular event reduction in non-diabetic obese individuals. The FLOW trial showed 24% kidney event reduction. The most-studied molecule in the incretin class. Read: GLP-1 Agonists →

Drugs that selectively kill senescent cells. The most studied combination is dasatinib + quercetin (D+Q). Human trials are in early stages. Considered one of the most promising novel longevity drug classes. Read: Longevity Science 2025 →

A class of diabetes drugs (empagliflozin, dapagliflozin) that block glucose reabsorption in the kidneys. Have shown dramatic cardiovascular and renal protective effects. Emerging evidence suggests anti-senescence properties. Read: Kidney Health →

A family of NAD+-dependent enzymes (SIRT1-7) that regulate DNA repair, metabolism, inflammation, and stress resistance. SIRT1 is the most studied for longevity. SIRT3 regulates mitochondrial function. Activated by NAD+ availability, exercise, and caloric restriction. Read: Sirtuins →

The cyclical structure of sleep across the night, alternating between NREM stages (N1, N2, N3/SWS) and REM sleep in approximately 90-minute cycles. First-half sleep is dominated by slow-wave sleep; second-half by REM. Read: Sleep Stages →

The deepest stage of non-REM sleep, characterized by high-amplitude delta waves. Essential for growth hormone secretion, tissue repair, immune function, and glymphatic brain clearance. Declines significantly with age. Read: Sleep Stages →

The discrepancy between social schedules (alarm clocks, work hours) and the body's circadian clock. Common in people who sleep later on weekends. Associated with metabolic disruption, increased BMI, and cardiovascular risk. Read: Circadian Rhythm →

The age-related decline in stem cell number and regenerative capacity. One of the 12 hallmarks of aging. Reduces the body's ability to repair tissue, maintain immune function, and replace damaged cells. Read: Hallmarks of Aging →

Elevated TSH (4.5-10 mIU/L) with normal free T4. Affects up to 15% of adults over 60. Treatment is controversial — some patients benefit from levothyroxine while others do not. Monitoring is recommended. Read: Thyroid Function →

The first FDA-approved randomized controlled trial designed to test a drug against aging as a composite endpoint. Testing metformin's ability to delay a composite of age-related diseases and mortality. Expected to set a regulatory precedent for aging as a treatable condition. Read: Metformin →

An enzyme that adds telomeric repeats to chromosome ends, partially counteracting telomere shortening. Active in stem cells and cancer cells. Lifestyle factors (exercise, stress reduction) modestly upregulate telomerase activity. Read: Telomeres →

Repetitive DNA sequences (TTAGGG) capping chromosome ends that shorten with each cell division. Critically short telomeres trigger cellular senescence. Telomere length testing is commercially available but has significant limitations as a longevity biomarker. Read: Telomeres →

The primary male sex hormone. Declines approximately 1-2% per year after age 30. The 2023 TRAVERSE trial established cardiovascular safety of TRT in hypogonadal men. Replacement is appropriate for symptomatic men with confirmed low levels. Read: Testosterone →

The thyroid gland produces T4 (thyroxine, inactive) and T3 (triiodothyronine, active). TSH from the pituitary stimulates production. Subclinical dysfunction is common and underdiagnosed in adults over 50. Read: Thyroid Function →

Confining all daily food intake to a specific window (typically 8-12 hours) without necessarily reducing total calories. Benefits are mediated through circadian alignment of metabolism. Early TRE (eating earlier in the day) appears superior to late TRE. Read: Time-Restricted Eating →

A dual GLP-1/GIP receptor agonist marketed as Mounjaro (diabetes) and Zepbound (weight management). Produced 22.5% weight loss in SURMOUNT-1. Outperformed semaglutide in head-to-head comparison (SURPASS-2). Cardiovascular outcome trial ongoing. Read: GLP-1 Agonists →

Blood fats that reflect recent dietary intake and metabolic health. Fasting triglycerides below 100 mg/dL are optimal for longevity. The TG:HDL ratio is a useful proxy for insulin resistance. Read: Bloodwork Guide →

The reduced (active) form of CoQ10 with superior bioavailability. Preferred over ubiquinone (oxidized form) for supplementation, particularly in individuals over 40 whose conversion capacity declines. Read: CoQ10 →

Industrially manufactured food products with five or more ingredients, typically including substances not used in home cooking (emulsifiers, artificial flavors, high-fructose corn syrup). Consistently associated with increased all-cause mortality in cohort studies. Read: Nutrition Blueprint →

An end product of purine metabolism. Elevated levels (>6.0 mg/dL in men, >5.0 in women) are causally linked to hypertension, kidney disease, and metabolic syndrome. Fructose consumption is the primary dietary driver. Read: Uric Acid →

A gut microbiome-derived metabolite of ellagic acid (from pomegranates, berries, walnuts). The most credible mitophagy-activating supplement with human trial data showing improved mitochondrial function and muscle endurance. Read: Mitochondria →

The longest cranial nerve, connecting the brainstem to the gut, heart, and lungs. The primary conduit of the parasympathetic nervous system. Vagal tone (measurable via HRV) is associated with anti-inflammatory capacity and stress resilience. Read: HRV →

Metabolically active fat surrounding abdominal organs. Unlike subcutaneous fat, visceral fat secretes inflammatory cytokines, drives insulin resistance, and is causally linked to cardiovascular disease. Can be elevated even in normal-weight individuals (MONW phenotype). Read: Visceral Fat →

A fat-soluble secosteroid hormone synthesized in the skin via UVB exposure. Deficiency affects 40-75% of adults. Optimal longevity range: 40-60 ng/mL. Influences bone health, immune function, and cancer risk. Read: Vitamin D →

Maximum oxygen uptake during exercise, measured in mL/kg/min. The single strongest predictor of all-cause mortality in the medical literature. Moving from the bottom 25th to the 50-75th percentile reduces mortality risk by 50-60%. Improvable at any age via Zone 2 and HIIT training. Read: VO2 Max →

Four transcription factors (Oct4, Sox2, Klf4, c-Myc) that can reprogram differentiated cells back to a pluripotent state. Partial reprogramming — brief expression without full dedifferentiation — has reversed epigenetic age in animal models. The most radical longevity frontier. Read: Yamanaka Factors →

Aerobic exercise at an intensity where fat oxidation is maximized and lactate remains below 2 mmol/L (approximately 60-70% of max heart rate). The most evidence-backed exercise modality for mitochondrial biogenesis, metabolic flexibility, and cardiovascular longevity. Recommended: 150-180 min/week. Read: Zone 2 Training →