Longevity Glossary

AMP-activated protein kinase. An enzyme that acts as a cellular energy sensor. When energy levels fall, AMPK activates to switch on energy-producing processes and switch off energy-consuming ones, including stimulating fat burning and promoting mitochondrial biogenesis. Activated by exercise, fasting, and metformin.

The set of metabolic processes that build larger molecules from smaller ones, requiring energy. Muscle protein synthesis is an anabolic process. Anabolism is promoted by adequate protein intake, resistance training, and sufficient sleep.

A protein found on the surface of LDL, VLDL, and lipoprotein(a) particles. Each atherogenic particle carries exactly one ApoB molecule, making it a more precise measure of cardiovascular risk than LDL cholesterol alone. High ApoB indicates a greater number of particles capable of entering arterial walls.

A measure of how rigid the walls of arteries have become with age. Stiff arteries force the heart to work harder, raise systolic blood pressure, and reduce the cushioning effect that absorbs each heartbeat. Assessed by pulse wave velocity. Reduced by aerobic exercise, smoking cessation, and blood pressure management.

A cellular self-cleaning process in which the cell breaks down and recycles damaged proteins, organelles, and pathogens. Derived from Greek meaning "self-eating." Declines with age. Stimulated by fasting, caloric restriction, exercise, and adequate sleep. Impaired autophagy is associated with neurodegeneration and cancer.

Brain-derived neurotrophic factor. A protein that supports the survival, growth, and maintenance of neurons. Often described as fertiliser for the brain. Exercise is the most potent stimulus for BDNF release. Low BDNF is associated with depression, cognitive decline, and Alzheimer's disease.

A measure of how old your body is at a physiological level, as distinct from your chronological age. Can be assessed through epigenetic clocks, biomarker panels, or functional tests including VO2 max, grip strength, and arterial stiffness. Biological age can be older or younger than chronological age depending on lifestyle factors.

The proportion of fat mass, lean mass (muscle, bone, water), and other tissues that make up body weight. Considered more clinically meaningful than body weight alone. Two individuals of identical weight and height can have dramatically different health profiles. Assessed by DEXA scan, bioimpedance analysis, or skinfold measurement.

A measure of calcium and other minerals per unit area of bone tissue. Declines with age, particularly rapidly in women in the decade after menopause. Low BMD is termed osteopenia; severe loss is osteoporosis. Resistance training, dietary calcium, vitamin D, and vitamin K2 all support bone density.

The set of metabolic processes that break down larger molecules into smaller ones, releasing energy. Muscle catabolism (the breakdown of muscle tissue for energy) becomes a concern during prolonged caloric restriction without adequate protein intake, severe illness, or immobilisation.

Your age in calendar years, from birth to today. Unlike biological age, chronological age cannot be altered. However, the gap between chronological and biological age is modifiable and is the central target of longevity medicine.

The approximately 24-hour internal biological clock that regulates sleep-wake cycles, hormone secretion, body temperature, and metabolism. Disrupted by shift work, travel across time zones, late-night light exposure, and irregular eating patterns. Aligning lifestyle with circadian biology is associated with improved metabolic and cardiovascular health.

The brain's ability to compensate for damage or age-related changes by using alternative neural networks or strategies. Built throughout life through education, social engagement, physical exercise, and cognitive challenge. Higher cognitive reserve is associated with a later onset of dementia symptoms despite equivalent brain pathology.

The primary glucocorticoid stress hormone, produced by the adrenal glands. Essential for waking response, immune function, and acute stress management. Chronically elevated cortisol from sustained psychological or physiological stress promotes visceral fat accumulation, muscle loss, immune suppression, and impaired sleep.

A protein produced by the liver in response to inflammation. High-sensitivity CRP (hs-CRP) is used as a marker of chronic low-grade inflammation, which underlies cardiovascular disease, type 2 diabetes, and cancer. A level above 3 mg/L is considered high risk. Reduced by aerobic exercise, dietary improvement, smoking cessation, and weight loss.

Dual-energy X-ray absorptiometry. A low-radiation imaging technique that precisely measures bone mineral density, lean mass, and fat mass, including visceral fat. Considered the gold standard for body composition assessment. Also used to detect osteoporosis and monitor muscle mass over time.

Dehydroepiandrosterone. A steroid hormone produced primarily by the adrenal glands. Serves as a precursor to testosterone and oestrogen. Peaks in the mid-twenties and declines steadily with age. Often used as a marker of adrenal function and overall hormonal ageing. Low levels are associated with fatigue, reduced libido, and loss of lean mass.

A form of resistance training that focuses on the lengthening phase of a muscle contraction, such as lowering a weight under control. Eccentric exercise produces greater muscle damage and subsequent adaptation than concentric work, making it particularly effective for building strength and treating tendinopathies such as Achilles and patellar tendinopathy.

A biological clock based on patterns of DNA methylation that predicts chronological and biological age with high accuracy. The Horvath clock and DunedinPACE are well-validated examples. The gap between epigenetic age and chronological age is associated with risk of age-related disease and all-cause mortality.

A blood measurement taken after 8 to 12 hours without food, reflecting baseline insulin secretion. Often more informative than fasting glucose for detecting early insulin resistance, as glucose can remain normal while insulin is already elevated to compensate. An optimal fasting insulin is typically below 8 mIU/L.

A protein that stores iron in cells. Serum ferritin is used as a proxy for iron stores. Low ferritin causes iron deficiency, impairing energy, cognition, and athletic performance. Very high ferritin is associated with inflammation, metabolic syndrome, and iron overload. The reference range is wide, and optimal levels for function are narrower than clinical ranges suggest.

The degree to which blood glucose levels fluctuate throughout the day. Assessed using continuous glucose monitors (CGM). High glucose variability, including frequent spikes and crashes, is associated with increased oxidative stress, inflammation, and long-term cardiovascular risk, even when average glucose appears normal.

A peptide hormone secreted by the pituitary gland that stimulates growth, cell reproduction, and regeneration. Critical for maintaining lean mass and bone density. Declines significantly with age. Secreted in pulses, primarily during deep slow-wave sleep. Exercise, adequate sleep, and fasting transiently raise GH levels.

The community of trillions of microorganisms, primarily bacteria, residing in the gastrointestinal tract. Influences digestion, immune function, inflammation, mood, and metabolic health. Diversity of microbial species is generally associated with better health outcomes. Shaped by diet, antibiotic use, stress, and birth and feeding history.

Glycated haemoglobin. A blood test that measures the proportion of haemoglobin molecules that have glucose attached to them, reflecting average blood glucose over approximately 90 days. Used to diagnose and monitor type 2 diabetes and prediabetes. An optimal HbA1c for longevity purposes is generally considered below 5.4%.

A framework first published in Cell in 2013 and updated in 2023 identifying the core biological processes that drive ageing, including genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, and chronic inflammation (inflammaging). Longevity interventions aim to slow or reverse one or more of these processes.

The period of life spent in good health, free from chronic disease and significant functional decline. Distinct from lifespan, which is total length of life. The primary aim of longevity medicine is to compress morbidity, extending healthspan to match lifespan. Increasing healthspan requires addressing physical, metabolic, and cognitive decline before it becomes symptomatic.

The variation in time intervals between consecutive heartbeats, measured in milliseconds. A higher HRV indicates a more responsive autonomic nervous system and is associated with better cardiovascular fitness, resilience to stress, and recovery. HRV declines with age, overtraining, chronic stress, poor sleep, and alcohol consumption.

Homeostatic model assessment of insulin resistance. Calculated from fasting glucose and fasting insulin. Used to quantify the degree of insulin resistance before type 2 diabetes develops. A HOMA-IR above 2.0 is associated with metabolic syndrome; above 2.9 indicates significant insulin resistance. Modifiable through diet, exercise, and sleep improvement.

An amino acid produced during the metabolism of methionine. Elevated homocysteine is an independent risk factor for cardiovascular disease, stroke, and dementia. Typically elevated when B vitamin status (B6, B12, folate) is insufficient. An optimal level is below 9 micromol/L. Readily reduced by B vitamin supplementation or dietary improvement.

An increase in muscle fibre size resulting from resistance training and adequate protein intake. Requires mechanical tension on muscle fibres, metabolic stress, and sufficient recovery. Stimulated by progressive overload. Becomes progressively harder to achieve with age, but remains possible into the eighth decade. The primary mechanism by which resistance training reverses sarcopenia.

Insulin-like growth factor 1. A hormone produced primarily in the liver in response to growth hormone signalling. Promotes cell growth, tissue repair, and muscle protein synthesis. Declines with age. Both very low and very high IGF-1 are associated with poor health outcomes; an optimal range exists. Influenced by diet quality, protein intake, and exercise.

The chronic, low-grade sterile inflammation that accumulates with biological ageing. Unlike acute inflammation, which is protective and resolves, inflammaging is persistent and drives cardiovascular disease, type 2 diabetes, cancer, neurodegeneration, and sarcopenia. Accelerated by obesity, poor diet, physical inactivity, sleep disruption, and smoking.

A condition in which cells respond less effectively to insulin, requiring the pancreas to produce more insulin to maintain normal blood glucose levels. A precursor to type 2 diabetes and a driver of metabolic syndrome, cardiovascular disease, and hormonal disruption. Reversed by exercise (particularly resistance training and Zone 2 cardio), dietary improvement, sleep, and weight loss.

The exercise intensity at which lactate begins to accumulate in the blood faster than it can be cleared. Training at or near the lactate threshold improves cardiovascular efficiency and extends the duration at which higher intensities can be sustained. Correlates strongly with endurance performance and VO2 max.

All body mass that is not fat, including muscle, bone, water, organs, and connective tissue. Skeletal muscle mass is the primary component of lean mass that is modifiable through exercise and diet. Preserving lean mass is among the most important physical strategies for maintaining function, metabolic health, and independence with ageing.

The minimum dose of the essential amino acid leucine required to maximally stimulate muscle protein synthesis (typically 2 to 3 grams per meal). Leucine is the principal anabolic trigger among the branched-chain amino acids. Foods richest in leucine include whey protein, animal muscle tissue, eggs, and dairy. Meeting the leucine threshold at each meal supports muscle preservation over 35.

Total length of life from birth to death. Human maximum lifespan is estimated at approximately 120 to 125 years. Average lifespan in the UK is around 79 years for men and 83 years for women. Extending lifespan without corresponding healthspan gains is not the goal of longevity medicine; compressing morbidity is.

A variant of LDL cholesterol with an additional apolipoprotein(a) protein attached. Highly atherogenic and largely genetically determined, making it resistant to dietary and lifestyle modification. One of the most significant independent cardiovascular risk factors, yet routinely omitted from standard lipid panels. A level above 50 mg/dL warrants active risk management.

A hormone produced by the pineal gland in response to darkness, signalling to the body that it is time to sleep. Declines significantly with age, which is partly responsible for the deterioration of sleep quality in later decades. Blue light exposure in the evening suppresses melatonin production. Not a sleeping pill; a circadian signal.

The ability to efficiently switch between burning carbohydrate and fat for fuel depending on availability and demand. Metabolically flexible individuals burn fat effectively at rest and during low-intensity exercise, and can rapidly shift to carbohydrate use during high-intensity effort. Impaired in insulin-resistant individuals. Improved by Zone 2 training, dietary variety, and fasting.

A cluster of metabolic abnormalities including central obesity (high waist circumference), high blood pressure, elevated fasting glucose, high triglycerides, and low HDL cholesterol. Presence of three or more criteria meets diagnostic threshold. Associated with a substantially increased risk of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease.

The capacity of mitochondria, the energy-producing organelles within cells, to generate ATP efficiently. Declines with age, contributing to reduced energy, impaired cellular repair, and accumulation of reactive oxygen species. Improved by aerobic exercise, resistance training, adequate sleep, and dietary antioxidants. Mitochondrial dysfunction is a recognised hallmark of ageing.

The process by which muscle cells build new protein, driven by resistance exercise and adequate protein intake. The net balance between MPS and muscle protein breakdown (MPB) determines whether muscle mass increases, stays constant, or declines. MPS response to protein is blunted with age, making higher total protein intakes and per-meal leucine thresholds more important after 35.

Nicotinamide adenine dinucleotide. A coenzyme essential to energy metabolism, DNA repair, and the activation of sirtuins. Declines significantly with age. Precursors including NMN and NR can raise NAD+ levels in cells. Currently an active area of longevity research.

The brain's ability to reorganise itself by forming new neural connections throughout life. Once thought to peak in childhood, neuroplasticity continues into old age, though it becomes less efficient. Enhanced by physical exercise, learning, social engagement, adequate sleep, and reduced chronic stress. Impaired by sedentary behaviour, alcohol, and chronic inflammation.

A group of steroid hormones (oestradiol, oestrone, oestriol) that regulate reproductive function, bone density, cardiovascular health, cognitive function, and mood. Declines sharply at menopause in women, driving bone loss, cardiovascular risk, and cognitive changes. Also present and physiologically relevant in men, where it declines more gradually with age.

A large class of plant compounds with antioxidant and anti-inflammatory properties. Include flavonoids (in berries, tea, cocoa), phenolic acids (in coffee, wholegrains), stilbenes (in red wine), and lignans (in flaxseeds). Associated with reduced risk of cardiovascular disease, type 2 diabetes, and neurodegenerative conditions in observational research.

The principle that training stimulus must increase over time, through greater load, volume, frequency, or complexity, to continue producing adaptation. Without progressive overload, the body adapts to a given stimulus and further progress stalls. The most fundamental principle of effective resistance training and the key to long-term strength and muscle gains.

Rapid eye movement sleep. A distinct sleep stage characterised by vivid dreaming, rapid eye movements, and near-complete muscle paralysis. Critical for emotional processing, memory consolidation, and brain cleaning. Typically occurs in longer periods towards the end of the sleep period. Suppressed by alcohol and many sleep medications.

The number of calories the body burns at complete rest to maintain essential physiological functions including breathing, circulation, and cell repair. Accounts for approximately 60 to 75 percent of total daily energy expenditure. Declines with age, partly due to loss of lean mass. Maintained by preserving muscle mass through resistance training and adequate protein intake.

The progressive loss of skeletal muscle mass, strength, and function associated with ageing. Begins in the fourth decade and accelerates after 60 without intervention. Strongly associated with frailty, falls, hospitalisation, metabolic disease, and all-cause mortality. The most evidence-based interventions are resistance training and adequate dietary protein.

Cells that have entered a permanent state of growth arrest in response to DNA damage, telomere shortening, or other stressors. Rather than dying, senescent cells remain metabolically active and secrete pro-inflammatory molecules (the senescence-associated secretory phenotype, or SASP), promoting tissue dysfunction. Accumulation of senescent cells is a hallmark of ageing.

Sex hormone-binding globulin. A protein that binds testosterone and oestrogen in the bloodstream, making them inactive. Only unbound (free) hormones are biologically active. High SHBG can cause symptoms of low testosterone or oestrogen even when total levels appear normal. Rises with age, alcohol, excess oestrogen, and thyroid disease.

A family of seven proteins (SIRT1 to SIRT7) that regulate gene expression, DNA repair, metabolism, and inflammation. Often called longevity proteins. Activated by NAD+ and by conditions of low energy availability such as fasting and exercise. Resveratrol is a well-publicised sirtuin activator, though evidence in humans remains limited.

A sleep disorder characterised by repeated episodes of partial or complete upper airway obstruction during sleep, causing oxygen desaturation and sleep fragmentation. Obstructive sleep apnoea (OSA) is underdiagnosed and associated with hypertension, cardiovascular disease, metabolic dysfunction, and cognitive decline. Treatable with CPAP therapy, positional therapy, or weight loss.

The structure and pattern of sleep stages across a full night, including light sleep (N1, N2), slow-wave sleep (N3), and REM sleep. Healthy sleep architecture cycles through these stages approximately every 90 minutes. Architecture is significantly disrupted by alcohol, sleep disorders, shift work, and ageing itself, which reduces slow-wave and REM sleep.

Also called deep sleep or N3 sleep. The most physically restorative sleep stage, during which growth hormone is released, tissue repair occurs, and the glymphatic system clears metabolic waste from the brain. Declines substantially with age and is disproportionately suppressed by alcohol. Essential for immune function, metabolic health, and memory consolidation.

Telomeres are protective caps on the ends of chromosomes, analogous to the plastic tips on shoelaces. They shorten with each cell division and with oxidative stress and inflammation. Short telomeres are associated with cellular senescence, increased disease risk, and shortened lifespan. Lifestyle factors including physical activity, dietary quality, and sleep can slow telomere attrition.

The primary male sex hormone, also present and physiologically important in women. In men, declines at approximately 1 to 2 percent annually from the mid-thirties. In women, peaks in the mid-twenties and falls progressively. Supports lean mass, bone density, libido, mood, cognitive function, and cardiovascular health. Assessed as total testosterone, free testosterone, and in context of SHBG.

An eating pattern that confines food intake to a defined window of time each day, typically 8 to 10 hours, without restricting total caloric intake. Aligns food intake with circadian biology. Associated with improved insulin sensitivity, blood pressure, and inflammatory markers in clinical trials. Distinct from intermittent fasting, which typically involves longer periods of complete caloric restriction.

Fat stored within the abdominal cavity, surrounding internal organs. Metabolically active and highly inflammatory, releasing cytokines and free fatty acids directly into the portal circulation. Strongly associated with insulin resistance, cardiovascular disease, and all-cause mortality. Reduced by sustained aerobic exercise, dietary improvement, and sleep. Not visible on the surface; assessed by waist circumference, DEXA scan, or CT imaging.

Maximal oxygen uptake. The maximum rate at which the cardiovascular system can deliver oxygen to working muscles, expressed as ml/kg/min. The single strongest predictor of all-cause mortality, outperforming blood pressure, cholesterol, smoking status, and diabetes in multiple large studies. Declines approximately 10 percent per decade after 30 without training. Increased by aerobic exercise, particularly interval training and Zone 2 training.

Sustained aerobic exercise at an intensity at which you can hold a conversation but find singing difficult, corresponding to approximately 60 to 75 percent of maximum heart rate. The most effective training zone for improving mitochondrial density, metabolic flexibility, and fat oxidation capacity. The foundation of longevity-focused exercise programming. Typically requires 150 to 180 minutes per week for meaningful cardiovascular and metabolic benefit.

Mechanistic target of rapamycin. A central cellular signalling hub that promotes protein synthesis, cell growth, and anabolism when activated. Stimulated by protein intake (especially leucine) and exercise. Chronically elevated mTOR is associated with accelerated ageing and cancer risk. Periodic suppression by fasting or caloric restriction activates autophagy and may extend healthspan.