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    The hallmarks of aging, explained

    The hallmarks of aging are a list of biological processes that scientists think drive aging, from DNA damage to chronic inflammation. The list grew from nine in 2013 to twelve in 2023.[1][2] The framework organises the field and points to drug targets, but researchers still disagree on what aging fundamentally is.[3][4]

    Editor reviewedStrict sourcingUpdated Aging and longevity biologyLife sciencesHealth and medicine

    What the hallmarks are

    Bodies wear out in many ways at once. To make sense of this, scientists grouped the changes into a short list of “hallmarks”: processes that show up in aging bodies across many species. A 2013 review proposed nine.[1] A 2023 update raised the number to twelve:[2]

    • Genomic instability: DNA damage builds up.[5]
    • Telomere attrition: the caps at the ends of chromosomes, called telomeres, deteriorate.[5]
    • Epigenetic alterations: chemical marks on DNA and its packaging, such as DNA methylation, change.[5]
    • Loss of proteostasis: cells get worse at keeping their proteins stable and working.[5]
    • Disabled macroautophagy: cells’ system for packaging damaged proteins and parts for disposal works less well.[5]
    • Deregulated nutrient sensing: growth and metabolism signals such as mTOR go awry.[6]
    • Mitochondrial dysfunction: the cell’s power plants produce energy less efficiently.[5]
    • Cellular senescence: damaged cells stop dividing but linger.[7][8]
    • Stem cell exhaustion: tissues lose their ability to renew.[5]
    • Altered intercellular communication: hormone and other signals between cells change.[5]
    • Chronic inflammation: low-grade inflammation, sometimes called inflammaging, persists.[5]
    • Dysbiosis: the gut microbe community, which shapes immunity and metabolism, shifts.[5]

    The plain-language descriptions above are simplified glosses on the scientific terms, based mainly on the 2013 review.[5]

    The 2013 framework listed genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication.[1] The 2023 revision added disabled macroautophagy, chronic inflammation and dysbiosis, bringing the total to twelve.[2] The authors stress that the hallmarks are interconnected, so a single intervention may act on several at once.[9]

    How a process qualifies

    Not every change seen in old age counts. To be a hallmark, a process must pass three tests: it shows up with age, making it worse in experiments speeds aging, and treating it can slow, stop or even reverse aging.[3] The third test is what makes the list useful for drug developers.

    The three criteria are age-associated manifestation, acceleration of aging when the process is experimentally accentuated, and deceleration, arrest or reversal of aging when it is therapeutically targeted.[3] The third criterion is demanding in practice. Much of the supporting evidence comes from short-lived model organisms, where gene variants that extend lifespan were first identified, and where the rate of aging is controlled partly by conserved pathways.[10][11]

    From hallmarks to treatments

    Each major intervention class in the field targets one or more hallmarks. Senolytic drugs aim to clear senescent cells; see senolytics.[12] Rapamycin acts on nutrient sensing through the mTOR pathway; see rapamycin-and-mtor.[13] Partial reprogramming tries to reset epigenetic alterations; see partial-reprogramming.[14]

    The reason this matters for medicine is that age-related decline is the main risk factor for cancer, diabetes, cardiovascular disease and neurodegeneration.[15] The geroscience hypothesis holds that slowing these processes could delay several of those diseases at once.[16]

    Limits of the framework

    The hallmarks are a map, not a settled theory. In a 2024 survey, aging researchers could not agree, even by majority, on what aging is, what causes it, when it starts or what counts as rejuvenation.[4]

    The 2024 survey authors argue that because different groups label different processes as “aging”, they prioritise different experiments, which partly explains why the field pursues so many targets in parallel.[17] A conclusive test that intervening on hallmarks helps people would need long trials with disease and mortality endpoints.[18] Next in the course: how epigenetic clocks work.

    Questions readers ask

    How many hallmarks of aging are there?

    Twelve, in the 2023 update of the framework. The original 2013 version listed nine.[2][1]

    What makes something a hallmark of aging?

    It has to appear with age, speed up aging when it is made worse experimentally, and slow, stop or reverse aging when it is targeted.[3]

    Why does aging matter for disease?

    Age-related decline is the main risk factor for major diseases including cancer, diabetes, cardiovascular disease and neurodegeneration.[15]

    Do scientists agree on what aging is?

    No. A 2024 survey of aging researchers found no majority view on what aging is, what causes it, or what counts as rejuvenation.[4]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      A 2013 review in Cell proposed nine tentative hallmarks of aging as common denominators across organisms: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. confirmedas of 2013-06-06

    2. [2]

      A 2023 update in Cell expanded the list to twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation and dysbiosis. confirmedas of 2026-10-10

    3. [3]

      In the 2023 framework a process counts as a hallmark if it shows up with age, if accentuating it experimentally speeds aging, and if intervening on it can slow, stop or reverse aging. confirmedas of 2026-10-10

    4. [4]

      A 2024 survey of aging researchers found no consensus, and not even a majority view, on core questions such as what aging is, what causes it, when it begins and what counts as rejuvenation. confirmedas of 2024-12-03

    5. [5]

      The 2013 hallmarks review describes the individual hallmarks: genetic damage that accumulates through life, telomeres that are especially prone to age-related deterioration, epigenetic changes such as altered DNA methylation, impaired protein homeostasis, a less efficient mitochondrial respiratory chain, senescence as a stable arrest of the cell cycle, declining regenerative potential of tissues, and changes in communication between cells, including a smoldering pro-inflammatory state called inflammaging; it also notes that the gut microbiome shapes immune function and metabolism. confirmedas of 2013-06-06

      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Genomic instability (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Telomere attrition (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Epigenetic alterations (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Loss of proteostasis (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Loss of proteostasis (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Mitochondrial dysfunction (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Cellular senescence (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Stem cell exhaustion (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Altered intercellular communication (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Altered intercellular communication (retrieved 2026-10-10)
      • The hallmarks of aging · Cell (Cell Press) (author manuscript or open full text in PubMed Central) · 2013-06-06 · Overview of interventions (retrieved 2026-10-10)
    6. [6]

      Inhibiting the mTOR pathway has extended lifespan in every species studied, as of a 2014 review of the evidence. confirmedas of 2014-12-24

    7. [7]

      Cellular senescence is a state in which damaged or dysfunctional cells stop dividing, which helps restrain tumour development. confirmedas of 2011-11-02

    8. [8]

      Senescent cells accumulate in many tissues with age and were hypothesized to disrupt tissue function through the factors they secrete. confirmedas of 2011-11-02

    9. [9]

      The authors of the 2023 hallmarks review describe the twelve hallmarks as interconnected with one another. confirmedas of 2026-10-10

    10. [10]

      Aging biology gained scientific credibility around 1989 with the discovery of gene variants that extend the lifespan of multicellular model organisms. confirmedas of 2019-07-10

    11. [11]

      The rate of aging is controlled, at least in part, by genetic pathways and biochemical processes that are conserved in evolution. confirmedas of 2013-06-06

    12. [12]

      Senolytics are a class of drugs designed to selectively kill senescent cells; the term was introduced in a 2015 paper that identified dasatinib and quercetin as candidates. confirmedas of 2015-04-22

    13. [13]

      In 2009 rapamycin, an inhibitor of the mTOR pathway, extended median and maximal lifespan in both male and female mice when feeding began at 600 days of age, the first drug shown to extend lifespan in both sexes of a mammal. confirmedas of 2009-07-08

    14. [14]

      In 2016, short-term cyclic expression of the four Yamanaka factors (partial reprogramming) improved hallmarks of aging and extended lifespan in a mouse model of premature aging. confirmedas of 2016-12-15

    15. [15]

      Age-related loss of physiological integrity is the primary risk factor for major human diseases including cancer, diabetes, cardiovascular disorders and neurodegenerative diseases. confirmedas of 2013-06-06

    16. [16]

      The geroscience hypothesis proposes that therapies slowing or reversing molecular changes of aging could delay or prevent multiple chronic diseases at once and extend healthy lifespan. confirmedas of 2023-02-09

    17. [17]

      The 2024 survey authors argue that because researchers label different processes as aging, they prioritise different experimental approaches. confirmedas of 2024-12-03

    18. [18]

      Researchers note that a conclusive test of the geroscience hypothesis requires long trials measuring hard endpoints such as chronic disease incidence and mortality. confirmedas of 2023-02-09

    Revision history (2)
    1. Page created.
    2. Refresh: the beginner glossary of the twelve hallmarks now cites the 2013 review's descriptions.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "The hallmarks of aging, explained." ContentLora, updated Oct 10, 2026. https://contentlora.com/explain/hallmarks-of-aging

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