What are the hallmarks of ageing, and what goes wrong in an ageing body?
In 2013 scientists listed nine ways cells and tissues break down with age. A decade later the list grew to twelve.
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The hallmarks of ageing are a checklist of the biological changes that show up in all organisms that age: damage to the genome, shortening , altered epigenetic marks, failing protein upkeep, and more. They were first listed in a landmark 2013 review by Carlos López-Otín and four colleagues, to capture the essence of biological ageing and its underlying mechanisms. Ageing is the primary risk factor for major human diseases, including cancer, diabetes, cardiovascular disorders and neurodegenerative diseases, so classifying what goes wrong is a first step to studying it.
The original list had nine hallmarks, sorted into three groups. Primary hallmarks are causes of damage: genome instability, telomere shortening, epigenetic alterations and loss of , the upkeep of proteins. Antagonistic hallmarks are responses to damage: deregulated nutrient sensing, mitochondrial dysfunction and cellular senescence. Integrative hallmarks are the results: stem cell exhaustion and altered communication between cells. In January 2023 the same authors updated the list to 12, adding macroautophagy, chronic inflammation and .
Causes and responses
- Primary: genome instability, telomere shortening, epigenetic alterations, loss of
- Antagonistic: nutrient sensing, , senescence
Results
- Integrative: stem cell exhaustion, altered cell communication
- Added in 2023: macroautophagy, chronic inflammation,
A few examples make them concrete. Damage to DNA forms mainly through oxidative stress and environmental factors, and the repair processes are imperfect, so damage accumulates over time. Each cell division shortens slightly, and division stops once they reach a critical length. And the proportion of senescent cells, dormant cells that no longer divide, increases with age.
The list is a framework, not a finished theory. A hallmark should also, when changed, slow the normal ageing process, but that last criterion is missing for many hallmarks, because science has not yet found feasible ways to amend these problems in living organisms.
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Recap
Ageing is a web of linked changes, sorted into causes, responses and results.
💡 A trick to remember it · Cause, cope, collapse: damage first, the body's response second, tissue failure last.
Surprising fact · For many hallmarks, nobody has yet found a feasible way to change them in living organisms.
Sources (2)
No source, no claim. Every fact in this lesson (18 claims) cites at least one of these.