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 → Source: PubMed

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 → Source: PubMed

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 → Source: PubMed

A Krebs cycle intermediate that declines with age. Supplementation extended lifespan and shortened the period of late-life illness in mice. Human evidence is limited to small, uncontrolled studies. Read: Supplements Guide → Source: PubMed

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 → Source: PubMed

A peptide that accumulates as plaques in Alzheimer's disease. In mice, its clearance from the brain increases during sleep. Whether amyloid drives the disease, rather than marking it, remains debated. Read: Alzheimer's Prevention → Source: PubMed

The age-related decline in the muscle's ability to build protein in response to amino acids and resistance training. Older muscle needs more protein per meal to respond fully: about 0.4 g/kg in older men versus about 0.24 g/kg in younger men. Read: Muscle Protein Synthesis → Source: PubMed

A protein present on every atherogenic lipoprotein particle (LDL, VLDL, IDL, Lp(a)). Because each particle carries one ApoB, it measures the number of these particles, and it can capture cardiovascular risk that LDL cholesterol misses when the two disagree. Read: ApoB → Source: PubMed

A gene with three common variants (ε2, ε3, ε4). In a large analysis of people of European ancestry, one ε4 copy raised Alzheimer's risk about 3-fold and two copies about 15-fold. Read: Longevity Genomics → Sources: PubMed · PubMed

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 → Source: PubMed

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 → Source: PubMed

A growth factor important for neuroplasticity, memory formation and neuronal survival. Exercise raises it: a single session has a moderate effect in meta-analyses, and regular training strengthens the response. Low levels are associated with depression and cognitive decline. Read: BDNF → Source: PubMed

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 → Source: PubMed

The process of breaking down fatty acids for energy in mitochondria. Increased by fasting, exercise and glucagon signalling, and central to metabolic flexibility. Read: GLP-1 Agonists → Source: PubMed

The proportion of a substance that reaches the circulation after you take it. Different forms of the same nutrient or drug can differ in how well they are absorbed. Read: Brand Testing → Source: Standard pharmacological definition (e.g., US FDA, 21 CFR 320.1)

An estimate of how old your body is functionally, as opposed to your chronological age. It is measured with epigenetic clocks (DNA methylation), blood biomarker algorithms or composite assessments, and it can differ from chronological age. Read: Biological Age Testing → Source: PubMed

Regions identified as having unusually many long-lived people: Okinawa (Japan), Sardinia (Italy), Nicoya (Costa Rica), Ikaria (Greece) and Loma Linda (California). Shared habits include plant-forward diets, daily movement and strong social ties. The accuracy of some of the underlying age records has been questioned. Read: Blue Zones → Source: PubMed

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 → Source: PubMed

A short-chain fatty acid produced when gut bacteria ferment dietary fiber. It is the main energy source for the cells lining the colon, supports the intestinal barrier and has anti-inflammatory effects. Read: Gut Microbiome and Longevity → Source: PubMed

A CT-based measurement of calcified plaque in the coronary arteries. A score of zero indicates a low 10-year risk of cardiovascular events. It is most useful for refining risk in adults whose risk is intermediate. Read: CAC Scoring → Source: PubMed

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 → Source: PubMed

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 → Source: PubMed

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 → Source: Attia P, Gifford B. Outlive: The Science and Art of Longevity. Harmony; 2023.

A wearable sensor that measures glucose in the fluid under the skin every few minutes. It shows patterns after meals and overnight that a single fasting glucose measurement misses. Read: CGM for Non-Diabetics → Source: PubMed

The number of years since birth. Distinct from biological age: two 50-year-olds can have quite different biological ages based on epigenetic and metabolic markers. Read: Biological Age Testing → Source: PubMed

The roughly 24-hour internal clock coordinated by the suprachiasmatic nucleus (SCN) in the brain. It regulates sleep and wake, hormone release, metabolism and gene expression. Long-term disruption, as in rotating night-shift work, is associated with higher cardiovascular risk. Read: Circadian Rhythm and Longevity → Source: PubMed

An electron carrier in the mitochondrial energy chain. Levels fall with age and with statin use. Ubiquinol is its reduced form; whether it is meaningfully better absorbed is debated, and supplements have not been shown to relieve statin muscle symptoms. Read: CoQ10 and Ubiquinol → Source: PubMed

The main stress hormone, produced by the adrenal glands. Chronically high cortisol, as in Cushing's syndrome, promotes visceral fat, muscle loss, high blood sugar and other features of metabolic syndrome. Read: Chronic Stress → Source: PubMed

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 → Source: PubMed

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 → Source: PubMed

The most-studied senolytic combination: dasatinib, a prescription cancer drug, and quercetin, a plant flavonoid. Small pilot trials in diabetic kidney disease and lung fibrosis reported fewer senescent-cell markers and showed the approach was feasible; larger trials are needed. Read: Longevity Science 2025 → Sources: PubMed · PubMed

A low-dose X-ray scan that measures bone density, lean mass and fat distribution. It is the standard test for osteoporosis and is widely used to measure muscle mass when assessing sarcopenia. Read: Bone Density → Source: PubMed

A marine omega-3 fatty acid and the most abundant omega-3 in the brain, important for neuronal membranes and signalling. Found in fatty fish and algal oil. Read: Omega-3 → Source: PubMed

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 → Source: PubMed

An enzyme that breaks down the gut hormones GLP-1 and GIP within minutes. Semaglutide was engineered to resist DPP-4 and to bind albumin, which together allow once-weekly dosing. Read: GLP-1 Agonists → Source: PubMed

A third-generation epigenetic clock developed by researchers at Duke and Columbia universities. Instead of estimating biological age, it estimates the current pace of biological aging from a single blood test. Read: Epigenetic Clocks → Source: PubMed

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 → Source: PubMed

An estimate of kidney function calculated from blood creatinine (and sometimes cystatin C), age and sex; the 2021 equations no longer use race. An eGFR below 60 mL/min/1.73 m² for three months or more indicates chronic kidney disease, and lower eGFR is associated with higher cardiovascular and all-cause mortality. Read: Kidney Health → Sources: PubMed · PubMed

How well the endothelium, the single layer of cells lining the blood vessels, controls vessel tone and blood flow. Endothelial dysfunction is an early step in atherosclerosis and can be detected before plaques cause symptoms. Read: Advanced CV Testing → Source: PubMed

A marine omega-3 fatty acid found in fatty fish and algal oil. A high-dose prescription form (icosapent ethyl) reduced cardiovascular events in high-risk patients on statins in the REDUCE-IT trial. With DHA, it makes up the omega-3 index. Read: Omega-3 → Sources: PubMed · PubMed

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 → Source: PubMed

The level of insulin in the blood after an overnight fast. A raised level can signal insulin resistance; in one large cohort, insulin sensitivity was already falling steeply in the five years before diabetes was diagnosed. Reference ranges vary by lab and assay. Read: Fasting Insulin → Source: PubMed

A five-day, low-calorie, plant-based eating plan designed to mimic some effects of fasting, developed in Valter Longo's lab. In a randomized trial, three monthly cycles lowered body weight, blood pressure and IGF-1. Read: Prolonged Fasting and FMD → Source: PubMed

A protein that stores iron; its blood level reflects the body's iron stores. Low ferritin indicates iron deficiency. High ferritin can reflect iron overload, but it also rises with inflammation, infection and liver disease. Read: Iron Status → Source: PubMed

Carbohydrates that the body cannot digest; gut bacteria ferment some of them into short-chain fatty acids such as butyrate. In a large analysis of cohort studies and trials, people eating 25 to 29 grams a day or more had lower mortality and heart disease risk than those eating less. Read: Gut Optimization → Source: PubMed

A gene encoding a transcription factor involved in stress resistance, DNA repair and autophagy. Certain FOXO3 variants were strongly associated with longevity in long-lived Japanese-American men in Hawaii, and the link has since been found in other populations. Read: Longevity Genomics → Source: PubMed

Reactive oxygen species are produced mainly by mitochondria. At low levels they act as signalling molecules; in excess they damage DNA, proteins and lipids. The older idea that their accumulation drives aging has not held up as a complete explanation. Read: Mitochondria → Source: PubMed

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 → Source: PubMed

A drug or intervention that targets the biology of aging itself rather than one disease. None is approved for aging; the proposed TAME trial of metformin was designed to test whether a drug can delay several age-related diseases at once. Read: Longevity Science 2025 → Source: PubMed

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 → Source: PubMed

A gut hormone released after eating that stimulates insulin, suppresses glucagon, slows stomach emptying and reduces appetite. Drugs that mimic it (GLP-1 receptor agonists such as semaglutide) are used for diabetes and obesity. Read: GLP-1 Agonists → Source: PubMed

How much blood glucose swings up and down over the day. In people with type 2 diabetes, large swings activated oxidative stress more than steady high glucose did; whether variability matters in people without diabetes is uncertain. Read: CGM → Source: PubMed

The brain's waste-clearance system, in which cerebrospinal fluid flows along channels around blood vessels. In mice it is most active during sleep and clears amyloid-beta; impaired clearance is implicated in Alzheimer's disease. Read: Brain Longevity Blueprint → Source: PubMed

A second-generation epigenetic clock built to predict time to death, using DNA methylation stand-ins for smoking history and several blood proteins. In its developers' validation cohorts it strongly predicted lifespan and healthspan. Read: Epigenetic Clocks → Source: PubMed

The maximum force of your hand grip. In a 17-country study, each 5 kg lower grip strength was linked to 16 percent higher mortality, and grip strength predicted death better than systolic blood pressure. Read: Grip Strength → Source: PubMed

A pituitary hormone released mostly during deep sleep; its secretion falls with age. Growth hormone treatment for aging remains controversial, because raising IGF-1 may carry long-term risks despite short-term effects on body composition. Read: Hormones → Source: PubMed

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 → Source: PubMed

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 → Source: PubMed

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 → Source: PubMed

A measure of average blood glucose over the previous two to three months. An HbA1c of 6.5% or higher indicates diabetes, and 5.7 to 6.4% indicates prediabetes. Read: Bloodwork Guide → Source: PubMed

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. Source: PubMed

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 → Source: PubMed

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 → Source: PubMed

The formation of new neurons in the hippocampus, a brain region central to memory. Whether, and how much, it continues in adult humans is debated: one 2018 study found it drops to undetectable levels after childhood, while another found it persists into old age. Read: Exercise and the Brain → Sources: PubMed · PubMed

An estimate of insulin resistance calculated from fasting insulin and fasting glucose (insulin in μIU/mL × glucose in mg/dL ÷ 405). There is no universal cut-off: thresholds vary with age, sex and population. Read: Fasting Insulin and HOMA-IR → Sources: PubMed · PubMed

An amino acid made in the methionine cycle. High levels are associated with cardiovascular disease and cognitive decline. Folate, B12 and B6 lower homocysteine, but trials found that lowering it did not prevent heart attacks. Read: Homocysteine → Source: PubMed

A dose-response pattern in which a low dose of a stressor (exercise, fasting, cold, heat, some plant compounds) triggers protective adaptations, while higher doses cause harm. Proposed as the basis of several longevity interventions. Source: PubMed

The first epigenetic clock to work across almost all tissues (2013). It uses 353 DNA methylation sites to estimate age and became the benchmark for later clocks. Read: Epigenetic Clocks → Source: PubMed

Replacement of declining sex hormones. For women under 60 or within 10 years of menopause without contraindications, guidelines support hormone therapy for hot flashes and to prevent bone loss; it is not recommended to prevent heart disease or other chronic conditions. Transdermal estradiol carries a lower risk of blood clots than oral forms. Read: HRT for Women → Sources: PubMed · PubMed · PubMed

The variation in time between successive heartbeats. Higher HRV generally reflects stronger parasympathetic (rest-and-digest) activity, and it is used to track stress, fitness and recovery. Read: HRV → Source: PubMed

A blood marker of inflammation made by the liver. It is used to refine cardiovascular risk. Read: Bloodwork Guide → Source: PubMed

A growth factor driven by growth hormone. It supports muscle and tissue growth, but lower IGF-1 signalling is linked to longer life in animals, and in a study of people aged 95 and older, lower IGF-1 predicted longer survival in women. Read: Centenarian Biology → Source: PubMed

The gradual decline of immune function with age, marked by a shrinking thymus, fewer new (naive) T cells, more senescent immune cells and weaker responses to vaccines. Read: Zinc and Immune Aging → Source: PubMed

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 → Source: PubMed

Chronic, low-grade inflammation that rises with age, fed by senescent cells, visceral fat, changes in the gut and immune aging. It is thought to contribute to many age-related diseases. Read: Inflammaging → Source: PubMed

A state in which cells respond less to insulin, so the body needs more insulin to keep blood glucose normal. It can be present years before type 2 diabetes is diagnosed: in one large cohort, insulin sensitivity was already falling steeply in the five years before diagnosis. Read: Fasting Insulin → Source: PubMed

Eating patterns that cycle between eating and fasting, such as 16:8 (eating within an 8-hour window) or 5:2 (two very-low-calorie days a week). In a year-long trial, adding time-restricted eating to calorie restriction did not increase weight loss. Read: Fasting Myths → Source: PubMed

Fuel molecules made by the liver during fasting or carbohydrate restriction. Beta-hydroxybutyrate (BHB) is also a signalling molecule: in mice it inhibits histone deacetylases and protects against oxidative stress. Read: Ketogenic Diet → Source: PubMed

The exercise intensity at which lactate starts to build up in the blood. Zone 2 training is usually set just below the first lactate threshold, an intensity at which fat burning is near its peak. Read: Zone 2 Training → Source: PubMed

An essential amino acid that switches on mTORC1 and muscle protein synthesis. Leucine-rich proteins such as whey stimulate muscle protein synthesis more than lower-leucine proteins at the same dose. Read: Muscle Protein Synthesis → Source: PubMed

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). Source: PubMed

A lipoprotein particle whose level is largely inherited and changes little with diet or exercise. Genetic and epidemiologic studies show a causal, continuous link between Lp(a) and cardiovascular disease, even when LDL cholesterol is very low. Drugs that lower Lp(a) are being tested in outcome trials. Read: Lp(a) → Sources: PubMed · PubMed

A composite endpoint that typically combines cardiovascular death, nonfatal heart attack and nonfatal stroke. It is the usual primary endpoint in cardiovascular outcome trials, although definitions vary between studies. Read: GLP-1 Agonists → Source: PubMed

An essential mineral needed by hundreds of enzymes, including those involved in energy production and nerve and muscle function. About half of US adults consume less than the estimated requirement. Read: Magnesium → Source: PubMed

The name adopted in 2023 for fatty liver disease linked to metabolic risk factors (formerly NAFLD). It affects about 30% of adults worldwide and can progress to MASH (inflammation), fibrosis and cirrhosis. Obesity, type 2 diabetes and insulin resistance are the main drivers. Read: Liver Health → Sources: PubMed · PubMed

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 → Source: Attia P, Gifford B. Outlive: The Science and Art of Longevity. Harmony; 2023.

A dietary pattern built on olive oil, vegetables, legumes, fruit, whole grains, fish and nuts. In the PREDIMED trial (republished in 2018 after problems with randomization were found), Mediterranean diets supplemented with olive oil or nuts lowered major cardiovascular events by about 30%. Read: Mediterranean Diet → Source: PubMed

A hormone made by the pineal gland in darkness that helps time sleep. In older adults, about 0.3 mg restored normal night-time levels; higher doses such as 3 mg raise levels far above normal. Read: Melatonin → Source: PubMed

A method that uses genetic variants as natural experiments to test whether an exposure causes an outcome, which reduces confounding. In a large Chinese study, genetic evidence showed that moderate drinking does not protect against stroke, and genetic studies support Lp(a) as a cause of heart attacks. Read: Alcohol and Longevity → Sources: PubMed · PubMed

The ability to switch between burning glucose and fat as fuel supply and demand change. Reduced flexibility accompanies insulin resistance and obesity. Read: Metabolic Flexibility → Source: PubMed

A diabetes drug that lowers glucose production by the liver. Observational and animal studies prompted interest in it as an anti-aging drug, and the proposed TAME trial would test whether it delays several age-related diseases at once. Read: Metformin → Source: PubMed

The active form of folate (vitamin B9). It does not need the MTHFR enzyme to be activated and is marketed to people with MTHFR variants, but medical genetics guidelines find no evidence to support MTHFR testing to guide treatment. Read: Folate vs Folic Acid → Source: PubMed

The variety of microbial species in the gut. Higher diversity is generally associated with better health; in one large study, a gut microbiome that became more distinctive with age predicted better survival in older adults. Read: Gut Microbiome → Source: PubMed

A hybrid of the Mediterranean and DASH diets designed for brain health, emphasizing berries, leafy greens, nuts, olive oil, fish and whole grains. In a three-year trial, it did not slow cognitive decline more than a control diet when both groups lost similar weight. Read: Mediterranean Diet → Source: PubMed

Organelles that produce most of the cell's energy (ATP). Mitochondrial dysfunction is one of the 12 hallmarks of aging. Endurance exercise increases mitochondrial content in muscle. Read: Mitochondria and Aging → Sources: PubMed · PubMed

The selective recycling of damaged mitochondria, essential for mitochondrial quality control. It is stimulated by exercise and fasting; in a human trial, urolithin A was safe and produced a molecular signature of improved mitochondrial function. Read: Mitochondria and Aging → Source: PubMed

People with a normal BMI who have metabolic abnormalities such as insulin resistance, high blood pressure or abnormal lipids. In US national data, about 1 in 4 normal-weight adults had two or more such abnormalities. Read: Visceral Fat → Source: PubMed

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. Source: PubMed

An enzyme that converts folate into its active form. A common variant, C677T, makes the enzyme less stable and less active and can raise homocysteine, especially when folate intake is low. Medical genetics guidelines do not support routine MTHFR testing. Read: Folate vs Folic Acid → Sources: PubMed · PubMed

A nutrient-sensing kinase that drives growth and protein synthesis when nutrients are plentiful. Inhibiting it with rapamycin extends lifespan in mice, even when started late in life; whether intermittent inhibition benefits people is not yet known. Read: mTOR → Sources: PubMed · PubMed

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 → Source: PubMed

Signalling molecules, such as IL-6, released by contracting muscle. They mediate some of the effects of exercise on metabolism and inflammation and underpin the idea of muscle as an endocrine organ. Read: Strength Training → Source: PubMed

A coenzyme essential for energy metabolism and for enzymes such as PARPs and sirtuins. NAD+ levels fall with age in several tissues; NMN and NR are precursors being studied as ways to restore it. Read: NAD+ and Sirtuins → Source: PubMed

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 → Source: PubMed

A direct precursor of NAD+. Human trials are small and short: in women with prediabetes it improved muscle insulin sensitivity, and trials have tested doses of up to 900 mg a day. Read: NMN vs NR → Sources: PubMed · PubMed

An NAD+ precursor that enters the salvage pathway through NRK enzymes. In a trial in healthy middle-aged and older adults, NR was well tolerated and raised NAD+ levels. Read: NMN vs NR → Source: PubMed

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 → Source: PubMed

The percentage of EPA plus DHA in red blood cell membranes. In the paper that proposed it, an index of 8% or more was associated with the lowest risk of death from coronary heart disease and 4% or less with the highest. Read: Omega-3 → Source: PubMed

A term coined in 2017 for sleep problems driven by a preoccupation with perfecting sleep-tracker data. Read: Sleep Tracking → Source: PubMed

DNA repair enzymes that consume NAD+ as they fix DNA breaks. Rising DNA damage with age increases their demand for NAD+, which may contribute to falling NAD+ levels. Read: NAD+ → Sources: PubMed · PubMed

A second-generation epigenetic clock (2018) trained on a blood-test-based measure of physiological age rather than on chronological age. It outperformed earlier clocks at predicting mortality and age-related disease. Read: Epigenetic Clocks → Source: PubMed

A large family of plant compounds (flavonoids, stilbenes, phenolic acids) found in berries, tea, cocoa, olive oil, coffee and vegetables. Their health effects are thought to come partly from triggering stress-response pathways rather than only from direct antioxidant activity. Read: Polyphenols → Sources: PubMed · PubMed

A Spanish randomized trial of 7,447 people at high cardiovascular risk. Mediterranean diets supplemented with extra-virgin olive oil or nuts reduced major cardiovascular events by about 30% compared with advice to follow a reduced-fat diet. The results were republished in 2018 after problems with randomization at some sites were corrected for. Read: Mediterranean Diet → Source: PubMed

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 → Source: PubMed

An mTOR inhibitor used to prevent organ-transplant rejection. It has extended lifespan in yeast, worms, flies and mice, including when started late in life in mice. Intermittent low-dose regimens are being studied in people, but there is no proof yet that it slows human aging. Read: Rapamycin and mTOR → Sources: PubMed · PubMed

The sleep stage with rapid eye movements, vivid dreams and near-total muscle paralysis. It is thought to support memory and emotional processing, and alcohol suppresses it early in the night. Read: Sleep Stages → Sources: PubMed · PubMed

A polyphenol found in grapes and red wine, once promoted as a sirtuin activator. Later research showed that some early test-tube results depended on the assay used, and in older Italian adults, dietary resveratrol levels were not associated with longer life. Current evidence does not support supplements for longevity. Read: Sirtuins → Sources: PubMed · PubMed

A triple receptor agonist (GLP-1, GIP and glucagon) that is not yet approved. It produced 24.2% weight loss at 48 weeks in a phase 2 trial; in the phase 3 TRIUMPH-1 trial, Lilly's topline results reported 28.3% average weight loss at 80 weeks on 12 mg (25.0% counting everyone who started). The glucagon component is thought to add effects on energy expenditure and liver fat. Read: GLP-1 Agonists → Sources: PubMed · Eli Lilly press release, May 21, 2026: TRIUMPH-1 topline results (investor.lilly.com) · PubMed

Age-related loss of muscle mass, strength and function. It is associated with falls, frailty, disability and higher mortality. Resistance training is the main countermeasure, alongside adequate protein. Read: Strength Training → Source: PubMed

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 → Source: PubMed

A cardiovascular outcome trial of 17,604 people with established cardiovascular disease and overweight or obesity but no diabetes. Semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% (hazard ratio 0.80). Published in the New England Journal of Medicine in 2023. Read: GLP-1 Agonists → Source: PubMed

A GLP-1 receptor agonist sold as Ozempic (diabetes) and Wegovy (weight management). In the SELECT trial it reduced major cardiovascular events by 20% in people with heart disease and overweight or obesity without diabetes, and in the FLOW trial it reduced serious kidney outcomes in people with diabetes and kidney disease by 24%. Read: GLP-1 Agonists → Sources: PubMed · PubMed

Drugs that selectively kill senescent cells. The most studied combination is dasatinib plus quercetin. Human trials are small and early. Read: Longevity Science 2025 → Source: PubMed

Diabetes drugs (such as empagliflozin and dapagliflozin) that make the kidneys excrete glucose. In large trials they reduced hospitalization for heart failure and the progression of kidney disease. Read: Kidney Health → Source: PubMed

A family of NAD+-dependent enzymes (SIRT1 to SIRT7) involved in DNA repair, metabolism and stress responses. Their activity depends on NAD+ levels, which fall with age; whether boosting them extends human life is unknown. Read: Sirtuins → Source: PubMed

The structure of sleep across the night, cycling through non-REM stages (N1, N2, N3) and REM sleep roughly every 90 minutes. Deep (slow-wave) sleep is concentrated in the first half of the night and REM sleep in the second half. Read: Sleep Stages → Source: PubMed

The deepest stage of non-REM sleep, marked by slow, high-amplitude delta waves. It declines markedly from early adulthood to midlife, in step with a fall in growth hormone secretion. Read: Sleep Stages → Source: PubMed

The mismatch between the sleep timing that work or social schedules impose and the timing your body clock prefers, often seen as sleeping much later on weekends. In a large population study, more social jetlag was associated with a higher BMI. Read: Circadian Rhythm → Source: PubMed

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 → Source: PubMed

A raised TSH (commonly 4.5 to 10 mIU/L) with normal free T4. It is common in older adults. In the TRUST trial of adults aged 65 and over, levothyroxine did not improve symptoms or tiredness, so monitoring is often preferred to treatment. Read: Thyroid Function → Sources: PubMed · PubMed

A proposed trial, designed with input from the FDA, to test whether metformin delays a composite of age-related diseases and death in older adults. Its aim is to establish delaying multiple age-related diseases as a valid trial endpoint. Read: Metformin → Source: PubMed

An enzyme that adds repeats to chromosome ends, partly offsetting telomere shortening. It is active in stem cells and most cancer cells. A small pilot study found higher telomerase activity after a comprehensive lifestyle program. Read: Telomeres → Sources: PubMed · PubMed

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 → Source: PubMed

The main male sex hormone. In a large cohort of older men, total testosterone fell by about 1.6% a year. The 2023 TRAVERSE trial found testosterone therapy noninferior to placebo for major cardiovascular events in men with low testosterone and high cardiovascular risk, with more atrial fibrillation, acute kidney injury and pulmonary embolism. Guidelines support treatment for men with symptoms and confirmed low levels. Read: Testosterone → Sources: PubMed · PubMed · PubMed

The thyroid gland produces T4 (thyroxine), which is converted in the body to the more active T3 (triiodothyronine); TSH from the pituitary stimulates production. Subclinical thyroid dysfunction is common in older adults. Read: Thyroid Function → Source: PubMed

Confining daily food intake to a set window, typically 8 to 12 hours. In a year-long trial, it added no weight-loss benefit beyond calorie restriction; a small controlled-feeding study found that eating early in the day improved insulin sensitivity even without weight loss. Read: Time-Restricted Eating → Sources: PubMed · PubMed

A dual GLP-1 and GIP receptor agonist sold as Mounjaro (diabetes) and Zepbound (weight management). In SURMOUNT-1 it produced up to 20.9% weight loss at 72 weeks; it outperformed semaglutide 1 mg in SURPASS-2, and in SURPASS-CVOT it was noninferior to dulaglutide for major cardiovascular events in people with type 2 diabetes and heart disease. Read: GLP-1 Agonists → Sources: PubMed · PubMed · PubMed

Fats carried in the blood; high levels add to cardiovascular risk. The triglyceride-to-HDL ratio has been used as a rough marker of insulin resistance. Read: Bloodwork Guide → Sources: PubMed · PubMed

The reduced form of CoQ10. It is often marketed as better absorbed than ubiquinone (the oxidized form), but the body converts readily between the two, and evidence that it works better in practice is limited. Read: CoQ10 → Source: PubMed

Industrial food products typically made with five or more ingredients, including substances rarely used in home cooking such as emulsifiers, flavourings and sweeteners. Higher intake is associated with higher all-cause mortality in cohort studies. Read: Nutrition Blueprint → Sources: PubMed · PubMed

The end product of purine breakdown. High levels cause gout and are associated with high blood pressure and kidney disease, but two trials of the urate-lowering drug allopurinol did not slow kidney function decline. Read: Uric Acid → Sources: PubMed · PubMed

A compound made by gut bacteria from ellagitannins in pomegranates, berries and walnuts. In small human trials it was safe, improved markers of mitochondrial function and, in one trial, improved some measures of muscle endurance. Read: Mitochondria → Sources: PubMed · PubMed

The longest cranial nerve, linking the brainstem with the heart, lungs and gut, and the main nerve of the parasympathetic system. Vagal signals can dampen inflammation (the inflammatory reflex), and vagal tone is often estimated from heart rate variability. Read: HRV → Source: PubMed

Fat stored around the abdominal organs. Compared with fat under the skin, it is more strongly linked to insulin resistance and cardiovascular disease, and genetic studies support a causal role. It can be raised even in people of normal weight. Read: Visceral Fat → Sources: PubMed · PubMed

A fat-soluble vitamin made in the skin with sunlight; blood 25(OH)D measures your status. Severe deficiency causes bone disease, but in large trials of generally healthy adults, such as VITAL, supplements did not reduce cancer or cardiovascular events. The Endocrine Society's 2024 guideline suggests against routine testing without an established reason and found no clear evidence for any target level. Read: Vitamin D → Sources: PubMed · PubMed

Maximum oxygen uptake during exercise, measured in mL/kg/min. It is among the strongest predictors of mortality: in a study of more than 122,000 patients, those with the lowest fitness had about five times the risk of death of the fittest. Read: VO2 Max → Source: PubMed

Four transcription factors (Oct4, Sox2, Klf4 and c-Myc) that can reprogram specialized cells back into stem cells. Brief, partial reprogramming has reversed signs of aging in mice; it has not been tested for aging in people. Read: Yamanaka Factors → Sources: PubMed · PubMed

Steady aerobic exercise just below the first lactate threshold, an intensity at which you can still talk and fat burning is near its peak. US guidelines recommend 150 to 300 minutes of moderate activity a week; Zone 2 is one way to meet them. Read: Zone 2 Training → Sources: PubMed · PubMed