The 12 hallmarks of ageing, in plain English

Ask a hundred people why we age and you'll get a hundred answers: wear and tear, bad genes, stress, bad luck. For most of history, ageing was simply what happened.

In 2013, a group of scientists tried something more ambitious: to name the underlying processes. They proposed nine "hallmarks of ageing". In 2023 they expanded the list to twelve.¹ To earn a place, a process had to change with age, speed ageing when made worse in experiments, and slow it when improved.

Here they are, grouped by what they do.

Damage: the things that accumulate

1. Genomic instability. DNA picks up damage and mutations over a lifetime. In one study, normal-looking tissue from older people was full of mutated cell clones.²

2. Telomere attrition. Telomeres are protective caps at the ends of chromosomes. They shorten as cells divide. But longer isn't simply better: genetic studies link longer telomeres to lower risk of some diseases and higher risk of some cancers.³

3. Epigenetic alterations. The marks that switch genes on and off drift with age. In a two-year trial, calorie restriction slightly slowed one "epigenetic clock" but not others.⁴

4. Loss of proteostasis. Cells lose their ability to fold proteins correctly and clear the broken ones. Misfolded proteins are central to diseases like Alzheimer's.⁵

Maintenance: the systems that falter

5. Disabled macroautophagy. Autophagy is cellular recycling: breaking down worn-out parts. It becomes less efficient with age. Human evidence that supplements boost it is limited.⁶

6. Deregulated nutrient-sensing. The pathways that tell cells whether food is plentiful (like mTOR) become miscalibrated. In one trial, briefly dampening mTOR with a drug improved older adults' response to a flu vaccine.⁷

7. Mitochondrial dysfunction. Mitochondria, the cell's power plants, become less efficient and less well maintained.⁸

8. Cellular senescence. Some damaged cells stop dividing but don't die. These "zombie cells" release signals that disturb their neighbours. Human trials of drugs to clear them are at a very early stage.⁹

Breakdown: the consequences that spread

9. Stem-cell exhaustion. The reserves that repair tissues decline. In older people's blood, production narrows to a few dominant stem-cell lines.¹⁰

10. Altered intercellular communication. Cells and organs signal to each other less accurately. Thousands of blood proteins shift with age, in waves rather than a straight line.¹¹

11. Chronic inflammation ("inflammaging"). Low-grade inflammation rises with age. A large trial showed that blocking one inflammatory pathway reduced heart attacks, but also increased fatal infections: a reminder of the trade-offs.¹²

12. Dysbiosis. The gut's microbial community changes. In older Europeans, a Mediterranean diet shifted gut bacteria in ways linked to lower frailty.¹³

What this map does, and doesn't, tell us

The hallmarks are useful because they're connected. DNA damage drives senescence; senescent cells drive inflammation; inflammation disturbs stem cells and the gut. Pull one thread and others move. That's why ageing appears across the whole body rather than in one organ.

But be wary when anyone says a product "targets all 12 hallmarks". The framework was built mostly from cell and animal research. In humans, we can see many hallmarks changing. Showing that changing one makes people live longer or healthier is a different, far harder question, and largely still open.

What we still don't know

• Which measurements truly predict healthy years of life?
• What trade-offs come from tinkering with growth, immunity or cell clearance?
• Can any intervention move several hallmarks at once in humans, and does it matter?