Skip to content
AlternativeMed
Healthy aging essentials: walking shoes, fresh vegetables, walnuts and a glass of water on a garden table

SPECIALTY TOPICS · GUIDE

Longevity and Aging Research Glossary

Plain-language definitions of common aging and longevity research terms, from biological age and senescence to surrogate endpoints, preprints and off-label use, with links to fuller guides.

Content last updated . This page has not been medically reviewed.

Back to Longevity and Healthy Aging: What the Evidence Supports

This glossary explains words you will meet in longevity and aging research. It is education only. A definition tells you what a term means in research, not whether a product or medicine works, and none of it is advice to start, stop or change any treatment. Evidence labels such as preclinical and promising but limited are explained on How We Label Evidence in Longevity Research.

Aging and age

  • Ageing (aging): at the biological level, the result of molecular and cellular damage building up over time, leading to a gradual decrease in physical and mental capacity and a growing risk of disease. [1] See What Is Aging?.
  • Chronological age: age in years. Health changes are only loosely associated with age in years. [1]
  • Biological age: an estimate of aging based on body measurements rather than the calendar. Researchers have studied epigenetic clocks, telomere length and other predictors, and a 2017 review said the true value of the epigenetic clock needs longitudinal confirmation. [2] See Biological Age vs Chronological Age.
  • Lifespan, healthspan, maximum lifespan: how long a life lasts, how many of those years are healthy, and the longest recorded life in a species. See Lifespan vs Healthspan vs Maximum Lifespan.
  • Geroscience: a field that aims to define and modify aging-related biologic pathways, slow age-related disability, prevent age-related diseases and increase disability-free survival. [3]
  • Hallmarks of aging: a framework of twelve features proposed in 2023, among them genomic instability, telomere attrition, cellular senescence and chronic inflammation. [4] It is a research framework, not a treatment map. See The Hallmarks of Aging.
  • Frailty: a state of vulnerability to poor recovery after a stressor event, resulting from cumulative decline in many body systems. [5]
  • Sarcopenia: described in a European consensus as a muscle disease (muscle failure) rooted in adverse muscle changes across a lifetime, with low muscle strength as a key feature. [6]
  • Inflammaging: chronic, sterile, low-grade inflammation that develops during aging and is thought to contribute to age-related disease. [7] See Inflammaging.

Cell and molecular terms

  • Cellular senescence: a cell state implicated in physiological processes and a wide range of age-related diseases. [8]
  • Senescence-associated secretory phenotype (SASP): factors released by senescent cells that can cause inflammation and dysfunction. [9]
  • Senolytic: a drug intended to remove senescent cells. In an open-label phase 1 pilot of dasatinib plus quercetin in nine people with diabetic kidney disease, cell markers fell, and the authors disclosed patents held by Mayo Clinic. [9] See Cellular Senescence Explained.
  • Autophagy: a self-degradative process that balances energy sources and removes misfolded proteins and damaged organelles. [10] See Autophagy Explained.
  • mTOR: a signaling pathway. Rapamycin, an inhibitor of the mTOR pathway, extended lifespan in genetically varied mice. [11] That is a mouse result, not a human one. See mTOR, AMPK and Nutrient-Sensing Pathways.
  • NAD+ and sirtuins: NAD is a coenzyme in metabolic pathways and a substrate for sirtuin enzymes. [12] A review said the clinical evidence that raising NAD+ improves physiological function is unclear. [13]
  • Telomere: the protective end of a linear chromosome. [14] See Telomeres and Aging.
  • DNA methylation and epigenetic clock: DNA methylation levels can be used to build predictors of age; one multi-tissue predictor used 353 sites. [15] Such clocks need validation before clinical use. [16]
  • DunedinPACE: a blood DNA methylation measure of the pace of aging, associated with illness, disability and death in its development study. [17] See Biological Age Clocks Compared.

Measures and endpoints

  • Biomarker: a measurable signal in the body. A biomarker of aging is not a health outcome, and no consensus exists on how such biomarkers should be validated before clinical use. [16]
  • Surrogate endpoint: a trial endpoint used as a substitute for a direct measure of how a patient feels, functions or survives. [18] See Surrogate Endpoints and Aging Biomarkers in Trials.
  • Clinical outcome: a direct measure of how a person feels, functions or survives. [18]
  • Disability-free survival: a combined endpoint used in the ASPREE trial: death, dementia or persistent physical disability. [19]

Study design terms

  • Preclinical: work in cells or animals. The National Institute on Aging Interventions Testing Program identifies agents that extend lifespan and healthspan in mice. [20]
  • Observational study: a study that does not test a medical intervention but watches people over time. [21]
  • Clinical trial: a study that tests a medical, surgical or behavioral intervention in people. [21] See Reading Longevity Studies.
  • Randomized trial: participants are randomly assigned to groups, such as aspirin or placebo. [19]
  • Pilot study: a small early study, such as a nine-person phase 1 trial. [9]
  • Systematic review and meta-analysis: a review that follows a stated method, and a statistical pooling of results. PRISMA is a reporting guideline for systematic reviews. [22] A 2023 physical activity paper is an example of a systematic review with a dose-response meta-analysis. [23]
  • Trial registration: listing a trial publicly before it enrolls people; the ICMJE says failing to do so risks inadmissibility to its journals. [24] See How to Find Longevity Studies and Trial Records.
  • Preprint and retraction: PubMed notes that preprints are among the citations not indexed for MEDLINE, and it has a Retracted Publication type. [25]
  • Conflict of interest: a financial or other stake in the result. One rapamycin trial disclosed that several authors were employees and shareholders of a company offering the medicine. [26]

Frequently asked questions

What is the difference between biological age and chronological age?

Chronological age is age in years. Biological age is an estimate based on measurements such as epigenetic clocks, telomere length and others. [2] No consensus exists on how aging biomarkers should be validated before clinical use. [16]

Is a biomarker the same as a health outcome?

No. A surrogate endpoint substitutes for a direct measure of how a person feels, functions or survives. [18] A biomarker change, such as a DNA methylation score, is not itself that outcome.

What does preclinical mean?

It means work in cells or animals. For example, the National Institute on Aging program tests agents in mice. [20] Such results are not evidence of benefit in people.

What does off-label mean?

It means use of an approved drug for an unapproved purpose. The FDA says providers generally may prescribe a drug this way when they judge it medically appropriate. [27] That is a decision for a prescriber, not a reader.

Where can I learn more about reading studies?

More details: evidence, limits and cautions

The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.

Medicines and regulation
  • Off-label use: use of an approved drug for an unapproved purpose. The FDA says that, once approved, healthcare providers generally may prescribe a drug for an unapproved use when they judge it medically appropriate. [27] See Off-Label Prescribing for Longevity.
  • Approved medicine: approved by a regulator for a named condition. For example, rapamycin is a drug approved to suppress organ rejection after transplant. [3]
  • Senotherapy: therapeutically targeting senescence to improve healthy aging and age-related disease; interest has grown rapidly, yet potential health benefits of reducing senescent cells in humans remain unclear. [8] [3]

For a bigger picture, see The Longevity Research Evidence Landscape.

References
  1. World Health Organization. Ageing and health, fact sheet, 1 October 2025. Read 2026-10-22.
  2. Jylhävä J, Pedersen NL, Hägg S. Biological age predictors. EBioMedicine 2017. PubMed 28396265. Read 2026-10-22.
  3. Kritchevsky SB, Cummings SR. Geroscience: a translational review. JAMA 2025. PubMed 40773213. Read 2026-10-22.
  4. López-Otín C et al. Hallmarks of aging: an expanding universe. Cell 2023. PubMed 36599349. Read 2026-10-22.
  5. Clegg A et al. Frailty in elderly people. Lancet 2013. PubMed 23395245. Read 2026-10-22.
  6. Cruz-Jentoft AJ et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019. PubMed 30312372. Read 2026-10-22.
  7. Franceschi C et al. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 2018. PubMed 30046148. Read 2026-10-22.
  8. Gorgoulis V et al. Cellular senescence: defining a path forward. Cell 2019. PubMed 31675495. Read 2026-10-22.
  9. Hickson LJ et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease. EBioMedicine 2019. PubMed 31542391. Read 2026-10-22.
  10. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol 2010. PubMed 20225336. Read 2026-10-22.
  11. Harrison DE et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009. PubMed 19587680. Read 2026-10-22.
  12. Ji LL, Yeo D. Maintenance of NAD+ homeostasis in skeletal muscle during aging and exercise. Cells 2022. PubMed 35203360. Read 2026-10-22.
  13. Freeberg KA et al. Dietary supplementation with NAD+-boosting compounds in humans. J Gerontol A 2023. PubMed 37068054. Read 2026-10-22.
  14. Shay JW, Wright WE. Telomeres and telomerase: three decades of progress. Nat Rev Genet 2019. PubMed 30760854. Read 2026-10-22.
  15. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol 2013. PubMed 24138928. Read 2026-10-22.
  16. Moqri M et al. Validation of biomarkers of aging. Nat Med 2024. PubMed 38355974. Read 2026-10-22.
  17. Belsky DW et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife 2022. PubMed 35029144. Read 2026-10-22.
  18. U.S. Food and Drug Administration. Surrogate Endpoint Resources for Drug and Biologic Development. Read 2026-10-22.
  19. McNeil JJ et al. Effect of aspirin on disability-free survival in the healthy elderly (ASPREE). N Engl J Med 2018. PubMed 30221596. Read 2026-10-22.
  20. National Institute on Aging. Interventions Testing Program (ITP). Read 2026-10-22.
  21. National Institute on Aging. What Are Clinical Trials and Studies?. Read 2026-10-22.
  22. PRISMA. Preferred Reporting Items for Systematic reviews and Meta-Analyses. Read 2026-10-22.
  23. Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose-response meta-analysis of large prospective studies. Br J Sports Med 2023. PubMed 36854652. Read 2026-10-22.
  24. International Committee of Medical Journal Editors. Clinical Trial Registration. Read 2026-10-22.
  25. National Library of Medicine. PubMed User Guide. Read 2026-10-22.
  26. Moel M et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging 2025. PubMed 40188830. Read 2026-10-22.
  27. U.S. Food and Drug Administration. Understanding Unapproved Use of Approved Drugs "Off Label". Read 2026-10-22.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.