Why does a twenty-year-old heal a cut in days, while an older person may need weeks? Why do heart disease, diabetes and dementia become more common as the years pass? For decades, ageing was seen as simple wear and tear. Today, scientists describe it as a set of twelve connected biological processes, known as the hallmarks of ageing.
Where the idea comes from
In 2013, a group of researchers led by Carlos López-Otín published a paper in the journal Cell listing nine shared features of ageing in mammals. In 2023, the same group updated the list to twelve, adding three: disabled autophagy (the cell's recycling system), chronic inflammation, and dysbiosis (an unhealthy gut microbiome).
To count as a hallmark, a feature should appear during normal ageing, make ageing faster when it is made worse in experiments, and slow ageing when it is corrected. The third condition is the hardest, so some hallmarks are better proven than others.
The twelve hallmarks in three levels
Level 1: the causes of damage
- Genomic instability: DNA is damaged every day by normal metabolism, sunlight and smoke. Most damage is repaired, but not all.
- Telomere attrition: telomeres are protective caps at the ends of chromosomes. They shorten each time a cell divides.
- Epigenetic alterations: chemical tags on DNA that switch genes on and off drift with time.
- Loss of proteostasis: more proteins fold badly and clump together.
- Disabled autophagy: the cell's recycling system slows down.
Level 2: the body's response
- Deregulated nutrient sensing: cells switch between a growth mode and a repair mode. Constant food and little movement keep the growth switch on.
- Mitochondrial dysfunction: the cell's power stations become less efficient.
- Cellular senescence: damaged cells stop dividing but stay alive and release irritating signals. Many people call them zombie cells.
Level 3: what we see and feel
- Stem cell exhaustion: the repair crew slows down.
- Altered cell communication: hormone and nerve signals become less clear.
- Chronic inflammation: a low, constant fire builds up in the body.
- Dysbiosis: the balance of gut bacteria shifts in an unhealthy direction.
What the research shows
Progeria. This very rare condition causes children to age extremely fast and is caused by an abnormal protein called progerin. In a 2018 study in JAMA, the death rate was 3.7% in children treated with the drug lonafarnib, compared with 33.3% in untreated children, over a median follow-up of about 2.2 years. This is important, but it applies to a rare disease, not to normal ageing.
Werner syndrome. A fault in a DNA-repair gene (WRN) leads to signs of ageing from the twenties. The median age of death is about 47 to 48 years, showing how important DNA repair is.
Epigenetic clocks. The Horvath clock uses 353 spots on the DNA to estimate age. It correlates with real age at 0.96, with a median error of about 3.6 years. Clocks are interesting research tools. We do not yet know whether changing the number improves health.
Zombie cells. In mice, transplanting only about one in 10,000 senescent cells into middle-aged animals was enough to cause frailty and earlier age-related disease. Medicines that clear these cells are being studied, but human results are still early.
Common myths
- "Nothing can be done about ageing." Many of these processes respond to lifestyle.
- "One pill fixes ageing." The hallmarks are connected, so a single fix is unlikely to be enough. Many products have only cell or mouse evidence.
- "A biological age test should decide my treatment." These tests are not yet proven for treatment decisions. Blood pressure, blood sugar, cholesterol and fitness are more useful.
- "Eating much less makes everyone live longer." Two large studies in monkeys disagreed on lifespan.
Four practical actions
- Move most days and add strength training twice a week.
- Protect your sleep. Keep a regular routine, and ask your doctor about loud snoring or constant tiredness.
- Feed your gut with vegetables, fruit, beans, nuts and whole grains, and eat less ultra-processed food.
- Know your numbers: blood pressure, blood sugar and cholesterol.
The bottom line
Ageing is not one single process. It is twelve linked ones, and daily habits influence many of them. Steady, simple actions beat dramatic shortcuts.
This article is for education only and is not personal medical advice. Please speak to your own doctor about your health.