Concepts & Frameworks

Antagonistic pleiotropy, formulated by evolutionary biologist George C. Williams in 1957, holds that genes selected for benefits early in life can cause harm later, after reproduction has occurred. Because selection pressure weakens with age, such alleles persist despite late-life costs. The hypothesis is a foundational explanation for why aging evolved and remains a leading evolutionary framework alongside mutation accumulation and disposable soma theory.

Biological age is an estimate of how old a person's body appears to be based on physiological and molecular markers, rather than the calendar. It can be derived from blood biomarkers (e.g. PhenoAge), DNA methylation patterns (epigenetic clocks), grip strength, gait speed or organ-specific proteomic signatures. Although widely used in longevity research, no single biological-age measure is yet endorsed by regulators as a clinical endpoint, and validation varies strongly between methods.

A centenarian is a person who has reached the age of 100 years or more. Centenarians are a key research population in longevity science because they typically delay or escape major age-related diseases. Studies such as the New England Centenarian Study and Japans Okinawa Centenarian Study examine genetic, lifestyle, and environmental factors associated with exceptional human lifespan and healthspan.

Chronological age is the time elapsed since a person's birth, usually measured in years. It is the standard reference variable in demography, medicine and epidemiology and remains one of the strongest single predictors of mortality and many age-associated conditions. Unlike biological age, chronological age does not capture variation in physiological decline between individuals; two people of the same chronological age may differ markedly in functional capacity, disease risk and remaining healthspan, and depending on cohort and endpoint other measures can match or exceed its predictive value.

Compression of morbidity is a concept introduced by James Fries in 1980 describing a scenario in which the onset of chronic disease and disability is postponed faster than the increase in lifespan, so that severe illness is concentrated into a shorter period at the end of life. It is a guiding goal of geroscience and healthspan-oriented medicine. Empirical evidence is mixed: in some populations morbidity has compressed, in others it has expanded as lifespan rose.

The disposable soma theory, proposed by Thomas Kirkwood in 1977, posits that organisms allocate finite metabolic resources between somatic maintenance and reproduction. Because natural selection favors reproductive success, the body invests only enough in repair to survive likely environmental hazards, leaving residual damage that accumulates as aging. The theory remains influential in evolutionary biogerontology and underlies modern thinking on caloric restriction and trade-offs.

The free radical theory of aging, proposed by Denham Harman in 1956, originally attributed aging to cumulative cellular damage from oxygen-derived free radicals, drawing on rate-of-living and oxygen-toxicity reasoning. Harman's 1972 update, the mitochondrial free radical theory of aging (MFRTA), specifically implicated mitochondrial ROS and mtDNA as the central drivers. While oxidative damage is undeniably involved, large antioxidant trials largely failed, and the theory is now considered partial. Modern frameworks integrate it with mitochondrial dysfunction and redox signaling.

Gerontology is the scientific study of aging across biological, psychological, and social dimensions. Established as a formal discipline in the early 20th century, with Ilya Mechnikov coining the term in 1903, it encompasses biogerontology, social gerontology, and geriatric medicine. It remains the broader umbrella field within which geroscience focuses specifically on molecular and cellular mechanisms relevant to disease prevention.

Geroscience is an interdisciplinary field that investigates the biological mechanisms of aging and their causal links to chronic disease. Coined around 2007 by researchers at the Buck Institute and formalized by the NIH-led Geroscience Interest Group, it rests on the premise that targeting aging itself can simultaneously delay multiple age-related conditions. It now underpins translational efforts like the TAME trial.

Healthspan is the period of life spent in good health, free from serious chronic disease and major functional impairment. It is conceptually distinct from lifespan, which counts total years lived. In longevity research healthspan is increasingly preferred as an outcome because the goal is to compress the years of frailty and disease at the end of life. Operational definitions vary and may use disease-free survival, disability indices or composite biomarker scores.

Lifespan is the total length of time an organism lives, from birth to death, typically expressed in years for humans. In population terms it is summarised by life expectancy at birth or at a given age. Maximum lifespan refers to the longest documented age reached within a species; for humans this is around 122 years. Lifespan is influenced by genetics, environment, behaviour and access to medical care, and is a classic outcome in longevity research.

Longevity escape velocity describes a hypothetical threshold at which medical advances extend remaining life expectancy by more than one year per calendar year, effectively outrunning aging. Popularized by biogerontologist Aubrey de Grey in the early 2000s, it remains a speculative concept rather than an empirically validated milestone. Mainstream geroscience treats it as an aspirational framing rather than a near-term forecast.

Negligible senescence describes organisms that show no measurable functional decline, increase in mortality risk, or loss of reproductive capacity with chronological age. The term was popularized by biogerontologist Caleb Finch in 1990 to characterize species such as certain rockfish, naked mole-rats, and hydra. It is studied as a comparative biology benchmark for understanding why most mammals, including humans, do age.

The reliability theory of aging, advanced by Leonid and Natalia Gavrilov in the early 1990s, applies engineering reliability mathematics to biological systems. It models organisms as redundant networks of components that fail stochastically; aging arises as redundancy depletes, producing the observed Gompertz mortality curve. The theory elegantly explains late-life mortality plateaus and provides a quantitative bridge between molecular damage and population-level survival data.

A supercentenarian is a person verified to have reached the age of 110 years or more. The 110+ threshold and term were popularized chiefly by L. Stephen Coles, founder of the Gerontology Research Group, with demographer James Vaupel contributing complementary validation work through MPIDR and the International Database on Longevity. The cohort numbers only a few hundred globally at any time and is studied for genetic resilience, late-life morbidity compression, and as a benchmark against unverified age claims.