Concepts

Allostatic Load

The 'wear and tear' on physiological systems from chronic stress responses. Quantified by composite biomarker scores; predicts mortality and disease independent of any single component.

APOE Genotype

The strongest common genetic risk factor for Alzheimer's disease and one of the most replicated longevity-related genetic loci.

Biological Age vs Chronological Age

Chronological age is how many birthdays you've had. Biological age is how old your body's molecular and physiological state seems compared to that.

Bradford Hill Criteria for Causation

Austin Bradford Hill's 1965 framework for inferring causation from observational data. Nine considerations (not a checklist) for moving from association to causal claim.

Centenarians and Supercentenarians

People who live to 100+ (centenarians) and 110+ (supercentenarians) offer a natural experiment in extreme longevity. Their biology and lifestyles are heavily studied.

Circadian Rhythm

The ~24-hour cycle that governs sleep, metabolism, hormone release, and gene expression. Misalignment (shift work, late-night light, irregular sleep) accelerates aging biology.

Confounding

A third variable that influences both exposure and outcome, distorting their apparent relationship. The dominant source of error in observational longevity research; the reason 'correlation is not causation' is repeated endlessly.

Geroprotector

A drug or intervention that targets fundamental aging biology to extend healthspan or lifespan. The umbrella term covering rapamycin, metformin, senolytics, NAD+ boosters, and similar candidates.

Geroscience Hypothesis

The unifying premise of modern aging research: that interventions targeting fundamental aging biology will delay multiple age-related diseases simultaneously.

Gompertz Law of Mortality

The empirical observation that adult human mortality rate doubles approximately every 8 years — a key constraint any theory of aging must explain or modify.

Hayflick Limit

The 1961 observation by Leonard Hayflick that normal human cells in culture divide ~50 times before stopping — overturning Carrel's incorrect 'immortal cell' dogma and seeding modern senescence and telomere biology.

Hazard Ratio

The ratio of event rates per unit time between groups. Most common effect-measure in survival analysis. Interpretable as a multiplicative shift in risk, with all the caveats of relative measures.

Healthspan vs Lifespan

Lifespan is years lived. Healthspan is years lived in good health. The longevity goal is to compress morbidity — extend healthspan to match lifespan.

Immunosenescence

Progressive remodelling and decline of the immune system with age. Drives weaker vaccine responses, infection susceptibility, cancer surveillance loss, and the inflammatory state of inflammaging.

Inflammaging (Concept)

The age-related rise in chronic, low-grade, sterile systemic inflammation. Predicts mortality and underlies most age-related diseases. Modifiable by lifestyle and emerging anti-inflammatory drugs.

Longevity Escape Velocity

Aubrey de Grey's idea that if life expectancy grows by more than one year per year of progress, individuals alive today could outpace death indefinitely.

Maximum Lifespan vs Life Expectancy

Life expectancy is the average age at death in a population. Maximum lifespan is the longest observed individual lifespan. They are different concepts with different determinants — and longevity science increasingly distinguishes them.

Mendelian Randomization

An epidemiological technique using genetic variants as 'natural experiments' to test causality. Because variants are randomly assigned at conception, MR mimics randomisation and avoids most confounding.

Negligible Senescence

Caleb Finch's term for species whose age-specific mortality and fertility don't decline measurably with age. Includes lobsters, certain rockfish, Hydra, and possibly Galapagos tortoises and bowhead whales.

NNT, ARR, RRR — Treatment-Effect Statistics

Relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT). Three numbers every reader of clinical evidence should understand to avoid being misled by impressive-sounding relative numbers.

Pace of Aging

A measure of how fast an individual is biologically aging right now, distinct from biological-age estimates of cumulative aging to date.

Partial Epigenetic Reprogramming

Brief expression of Yamanaka factors (OSK/OSKM) to reset epigenetic age without converting cells to pluripotency. The most-bet-on rejuvenation strategy in current longevity biotech.

Reserve & Robustness

Reserve is the spare physiological capacity available to withstand stressors. Robustness is the capacity to resist stress without losing function. Building reserve in midlife is the most actionable longevity strategy.

Senomorphic

Drugs that silence the senescence-associated secretory phenotype (SASP) without killing senescent cells. An alternative to senolytics with different risk-benefit profile.

Senotherapeutic

Umbrella term for drugs targeting senescent cells. Two branches: senolytics (kill senescent cells) and senomorphics (silence SASP without killing them).

Survivorship Bias

The systematic distortion that comes from only studying those who survived. Pervasive in longevity research: studying centenarians, drug-trial completers, and 'super-agers' over-represents protective features by selection.