The 12 hallmarks of aging
The framework scientists use to describe what goes wrong in cells and tissues as we age.
VALREXA Biosciences · 9 min read · November 2026
- In 2013, and again in 2023, researchers grouped the biology of aging into a set of “hallmarks.”
- The 2023 update lists 12, in three groups: primary, antagonistic and integrative.
- Each hallmark worsens with age, speeds aging when made worse in experiments, and slows aging when improved.
Where the framework comes from
In 2013 Carlos López-Otín and colleagues published “The Hallmarks of Aging” in Cell, proposing nine shared features of aging across organisms. It became one of the most cited papers in biology. In 2023 the same group expanded the list to twelve. To qualify, a hallmark must (1) appear with age, (2) speed aging when experimentally worsened, and (3) slow aging when experimentally improved.
The twelve hallmarks
| Group | Hallmark | In plain language |
|---|---|---|
| Primary: the causes of damage | Genomic instability | DNA damage builds up faster than it is repaired |
| Telomere attrition | The protective caps on chromosomes shorten with each cell division | |
| Epigenetic alterations | The chemical tags that control which genes are on or off drift with age | |
| Loss of proteostasis | Cells become worse at folding proteins and clearing damaged ones | |
| Disabled macroautophagy | The cell’s recycling system slows down (new in 2023) | |
| Antagonistic: responses that turn harmful | Deregulated nutrient sensing | Growth pathways such as insulin/IGF-1 and mTOR stay too active |
| Mitochondrial dysfunction | The cell’s power plants produce less energy and more damaging byproducts | |
| Cellular senescence | Damaged cells stop dividing but linger and release inflammatory signals | |
| Integrative: effects on tissues and the body | Stem cell exhaustion | Tissues lose the ability to renew themselves |
| Altered intercellular communication | Signals between cells, hormones and nerves become disordered | |
| Chronic inflammation | A persistent, low-grade inflammation sometimes called “inflammaging” (new in 2023) | |
| Dysbiosis | The gut microbiome changes in ways linked to disease (new in 2023) |
Why this matters
The hallmarks give researchers a shared map. Instead of treating heart disease, dementia and frailty separately, the geroscience hypothesis proposes that targeting the underlying biology of aging could delay many age-related diseases at once. Most interventions aimed at the hallmarks have been tested only in cells and animals; see our longevity evidence tracker for where the human evidence stands.
Limits of the framework
The hallmarks overlap and interact, and critics point out that the list describes features of aging more than it proves which ones cause it. Most of the experimental support comes from yeast, worms, flies and mice.
Check yourself
Name the three groups of hallmarks.
Which three hallmarks were added in 2023?
What are the three criteria for a hallmark?
Sources and further reading
- López-Otín et al. 2023. Hallmarks of aging: an expanding universe. Cell 186:243–278
- López-Otín et al. 2013. The hallmarks of aging. Cell 153:1194–1217
- Kennedy et al. 2014. Geroscience: linking aging to chronic disease. Cell
VALREXA Biosciences. (2026, November 7). The 12 hallmarks of aging. VALREXA Biosciences. https://valrexa.com/longevity/hallmarks-of-aging.html
APA style · Last reviewed November 7, 2026 · Our editorial standardsEducational content, not medical advice. Talk to a qualified healthcare professional before making changes to your health routine.