Interactive Tool

The 12 Hallmarks of Aging

The framework scientists use to describe what drives aging, as updated in 2023. Explore each hallmark and the human studies that have tested interventions against it.

12
Hallmarks
11
Interventions tested in people
3
Categories, as in the 2023 review
Explore the Framework
Click any hallmark to explore it
The 2023 review groups the hallmarks in three categories: primary hallmarks that cause damage, antagonistic hallmarks that respond to it, and integrative hallmarks that arise when the damage can no longer be compensated.
Primary hallmarks — causes of damage
They damage cells, and their effects are unequivocally negative.[1]
01
Genomic Instability
DNA damage builds up
1 intervention tested in people
02
Telomere Attrition
Chromosome ends shorten
1 intervention tested in people
03
Epigenetic Alterations
Gene-control marks drift
1 intervention tested in people
04
Loss of Proteostasis
Protein quality control fails
No human intervention studies yet
05
Disabled Macroautophagy
Cellular recycling declines
1 intervention tested in people
Antagonistic hallmarks — responses to damage
Responses to damage whose effects depend on their intensity.[1]
06
Deregulated Nutrient-Sensing
Nutrient signaling changes
2 interventions tested in people
07
Mitochondrial Dysfunction
Energy production falters
1 intervention tested in people
08
Cellular Senescence
Damaged cells stop dividing
1 intervention tested in people
Integrative hallmarks — when damage is no longer compensated
They arise when the damage from the other hallmarks can no longer be compensated.[1]
09
Stem Cell Exhaustion
Tissue repair declines
No human intervention studies yet
10
Altered Intercellular Communication
Cell signaling changes
No human intervention studies yet
11
Chronic Inflammation
Low-grade inflammation rises
2 interventions tested in people
12
Dysbiosis
Gut microbiome shifts
1 intervention tested in people
Human studies by hallmark
Which interventions have been tested against which hallmark?
Each mark is a human study listed in that hallmark's panel: T = trial, P = pilot trial, PT = prevention trial. A blank cell means no qualifying human study, not that the intervention has no effect.
Go Deeper
Read our article on all 12 hallmarks, or build a sourced starting plan.
Full Hallmarks Article → Build a Protocol → Supplement Database →

All 12 hallmarks at a glance

The same information as the explorer above, on one page: what each hallmark is, according to the 2023 review, and which interventions have been tested in people.

01. Genomic Instability Primary

DNA is constantly challenged by outside physical, chemical and biological agents and by internal threats, and genetic damage accumulates throughout life.[1]

  • Regular sunscreen use (Prevention trial): In a randomized trial with long-term follow-up, regular sunscreen use reduced melanoma.[4]

Read more: The Hallmarks of Aging: A Plain-Language Guide to the 12 Biological Processes Driving Your Decline

02. Telomere Attrition Primary

Telomeres, the protective ends of chromosomes, shorten as cells divide, and most adult body cells do not make telomerase, the enzyme that maintains them.[1]

  • Endurance and interval training (Trial): In a randomized trial, endurance and interval training, but not resistance training, increased telomerase activity and telomere length in circulating white blood cells.[5]

Read more: Telomeres and Longevity: What They Actually Tell Us - and What They Do Not · The Hallmarks of Aging: A Plain-Language Guide to the 12 Biological Processes Driving Your Decline

03. Epigenetic Alterations Primary

The chemical marks that control which genes are switched on change in all cells and tissues throughout life.[1]

  • Calorie restriction (Trial): In the two-year CALERIE trial, calorie restriction slowed the DunedinPACE pace of aging but did not change the PhenoAge or GrimAge clocks.[6]

Read more: Epigenetic Clocks Explained: How Scientists Estimate Biological Age, and the Limits · Biological Age Testing: Which Epigenetic Clocks Are Worth Using · Yamanaka Factors and Partial Reprogramming: The Science of Cellular Age Reversal

04. Loss of Proteostasis Primary

Aging and some age-related diseases are linked to impaired protein homeostasis: cells become worse at keeping proteins correctly folded and clearing damaged ones.[1]

No intervention targeting this hallmark has been tested in people yet.

Read more: Autophagy: How Your Cells Self-Clean — and Why It Matters for Longevity · Sauna and Longevity: The Finnish Evidence Behind Heat Therapy · Time-Restricted Eating: A Complete Evidence Review — Benefits, Optimal Windows, and Who It's Not For

05. Disabled Macroautophagy Primary

Autophagy, one of the systems cells use to clear and recycle damaged proteins and other components, declines with aging;[1] the 2023 review made it a hallmark of its own.[2]

  • Spermidine (Trial): Spermidine raised autophagy in the hearts of mice,[7] but in a 12-month trial in older adults it did not change memory or biomarkers compared with placebo.[8]

Read more: Autophagy: How Your Cells Self-Clean — and Why It Matters for Longevity · Time-Restricted Eating: A Complete Evidence Review — Benefits, Optimal Windows, and Who It's Not For

06. Deregulated Nutrient-Sensing Antagonistic

The pathways that sense nutrients, including insulin/IGF-1 signaling and mTOR, shape lifespan: variants that reduce their activity have been linked to longevity in humans and in model organisms.[1]

  • Calorie restriction (Trial): Two years of moderate calorie restriction reduced several cardiometabolic risk factors in non-obese adults.[9]
  • Rapamycin (prescription) (Trial): In the PEARL trial, low-dose intermittent rapamycin for 48 weeks was relatively safe in healthy adults and was linked to gains in lean tissue mass and less pain in women.[10]

Read more: Metformin for Longevity: The TAME Trial and What We Are Actually Testing · Time-Restricted Eating: A Complete Evidence Review — Benefits, Optimal Windows, and Who It's Not For · Fasting Insulin and HOMA-IR: The Biomarkers That Catch Metabolic Disease Decades Early

07. Mitochondrial Dysfunction Antagonistic

As cells and organisms age, the respiratory chain in mitochondria works less efficiently, leaking more electrons and making less ATP.[1]

  • Interval training (Trial): In young and older adults, interval training reversed many age-related differences in muscle proteins, particularly mitochondrial proteins.[11]

Read more: Mitochondria and Aging: Why the Decline of Your Cellular Power Plants Is Aging — and What to Do About It · Zone 2 Training: The Complete Science and Protocol for Metabolic Health and Longevity

08. Cellular Senescence Antagonistic

Cellular senescence is a stable arrest of the cell cycle coupled to typical changes in how the cell behaves.[1]

  • Dasatinib plus quercetin (Pilot trial): A short course of this drug combination reduced senescent cells in fat tissue within 11 days in people with diabetic kidney disease,[12] and in an open-label pilot in 14 people with lung fibrosis, physical function improved.[13]

Read more: Cellular Senescence: What “Zombie Cells” Are and What the Human Evidence Shows · The Hallmarks of Aging: A Plain-Language Guide to the 12 Biological Processes Driving Your Decline

09. Stem Cell Exhaustion Integrative

The regenerative potential of tissues declines, one of the most obvious characteristics of aging.[1]

No intervention targeting this hallmark has been tested in people yet.

Read more: The Hallmarks of Aging: A Plain-Language Guide to the 12 Biological Processes Driving Your Decline · Strength Training for Longevity: What Muscle Strength Predicts and How to Build It

10. Altered Intercellular Communication Integrative

Aging changes how cells signal to each other, whether through hormones, neuroendocrine pathways or nerves.[1]

No intervention targeting this hallmark has been tested in people yet.

Read more: Inflammaging: How Chronic Low-Grade Inflammation Is Linked to Age-Related Disease · The Mediterranean Diet for Longevity: What the Strongest Evidence in Nutrition Science Actually Shows

11. Chronic Inflammation Integrative

A smoldering, low-grade inflammation, often called inflammaging, accompanies aging.[1]

  • Canakinumab (prescription) (Trial): In people with a previous heart attack and raised hs-CRP, this anti-inflammatory antibody lowered recurrent cardiovascular events but raised fatal infections.[14]
  • Calorie restriction (Trial): About 14% calorie restriction for two years improved thymopoiesis, the production of new T cells; in mice, deleting a gene the study identified, Pla2g7, protected against age-related inflammation.[15]

Read more: Inflammaging: How Chronic Low-Grade Inflammation Is Linked to Age-Related Disease · Chronic Stress, Cortisol, and Aging: The Longevity Cost of Always Being On · The Sleep Optimization Guide: The Evidence-Based Strategies in One Place

12. Dysbiosis Integrative

The gut microbiome changes; in older adults, its composition has been linked to frailty, other illnesses, nutrition and markers of inflammation.[3]

  • Fermented foods (Trial): In a diet trial, eating more fermented foods steadily increased gut microbiome diversity and lowered inflammatory markers.[16]

Read more: The Gut Microbiome Guide: What Shapes It and What the Health Evidence Shows · The Hallmarks of Aging: A Plain-Language Guide to the 12 Biological Processes Driving Your Decline

Method, limits and how to read your result

How it works

The explorer walks through the twelve hallmarks of aging proposed in the 2023 update of the framework (reference 2). For each hallmark, it lists an intervention only when a human study measured it against that hallmark, labelled by study type.

Limits

The hallmarks are a research framework, not a diagnosis, and much of the underlying evidence comes from animal studies. The human trials listed are often small: early senolytic studies, for example, were a preliminary report in diabetic kidney disease and an open-label pilot in 14 people with lung fibrosis (references 12 and 13).

How to read your result

Use the labels to judge strength: a pilot trial is a first step, not proof of benefit. A hallmark with no qualifying human study shows where the science is still early, not that nothing matters.

How this explorer is built

The twelve hallmarks and their three categories follow the 2023 update of the hallmarks of aging,[2,18] and the definitions draw on the original 2013 review.[1]

Each hallmark lists an intervention only when a human study measured it against that hallmark, labelled "Trial", "Pilot trial" or "Prevention trial", with the study cited. Where no study qualifies, the panel says so. This page used to grade 66 interventions from A to D, defined as "A = strong human RCTs", without sources, and offered a "coverage" score for your routine; we removed both because the mappings behind them were not supported by human studies.

References

  1. 1López-Otín C, et al. "The hallmarks of aging." Cell. 2013;153(6):1194-217. PubMed · DOI
  2. 2López-Otín C, et al. "Hallmarks of aging: An expanding universe." Cell. 2023;186(2):243-278. PubMed · DOI
  3. 3Claesson MJ, et al. "Gut microbiota composition correlates with diet and health in the elderly." Nature. 2012;488(7410):178-84. PubMed · DOI
  4. 4Green AC, et al. "Reduced melanoma after regular sunscreen use: randomized trial follow-up." J Clin Oncol. 2011;29(3):257-63. PubMed · DOI
  5. 5Werner CM, et al. "Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study." Eur Heart J. 2019;40(1):34-46. PubMed · DOI
  6. 6Waziry R, et al. "Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial." Nat Aging. 2023;3(3):248-257. PubMed · DOI
  7. 7Eisenberg T, et al. "Cardioprotection and lifespan extension by the natural polyamine spermidine." Nat Med. 2016;22(12):1428-1438. PubMed · DOI
  8. 8Schwarz C, et al. "Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline: A Randomized Clinical Trial." JAMA Netw Open. 2022;5(5):e2213875. PubMed · DOI
  9. 9Kraus WE, et al. "2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial." Lancet Diabetes Endocrinol. 2019;7(9):673-683. PubMed · DOI
  10. 10Moel M, et al. "Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results." Aging (Albany NY). 2025;17(4):908-936. PubMed · DOI
  11. 11Robinson MM, et al. "Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans." Cell Metab. 2017;25(3):581-592. PubMed · DOI
  12. 12Hickson 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;47:446-456. PubMed · DOI
  13. 13Justice JN, et al. "Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study." EBioMedicine. 2019;40:554-563. PubMed · DOI
  14. 14Ridker PM, et al. "Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease." N Engl J Med. 2017;377(12):1119-1131. PubMed · DOI
  15. 15Spadaro O, et al. "Caloric restriction in humans reveals immunometabolic regulators of health span." Science. 2022;375(6581):671-677. PubMed · DOI
  16. 16Wastyk HC, et al. "Gut-microbiota-targeted diets modulate human immune status." Cell. 2021;184(16):4137-4153.e14. PubMed · DOI
  17. 17Conboy IM, Rando TA. "Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches." Cell Cycle. 2012;11(12):2260-7. PubMed · DOI
  18. 18Milosic F, et al. "Premature aging in genetic diseases: what conclusions can be drawn for physiological aging." Front Aging. 2023;4:1327833. PubMed · DOI
Medical Disclaimer: This tool provides educational information about the biology of aging. The studies listed reflect published research and are not medical recommendations. Full disclaimer →