The hallmarks of ageing: a practical map
The hallmarks of ageing are a scientific framework that breaks the messy biology of getting older into a short list of measurable, interconnected processes. First set out by Carlos Lopez-Otin and colleagues in 2013 as nine hallmarks, and expanded to twelve in 2023, they are the field's best attempt to answer one question: what actually changes inside us as we age, and which of those changes drive disease. They are a map of mechanisms, not a treatment plan. Most interventions aimed at them are not proven to extend human lifespan, but the framework is still the clearest way to see why ordinary habits like exercise, sleep and not smoking matter.
Key facts
- The original 2013 paper in Cell proposed nine hallmarks of ageing; the 2023 update, "Hallmarks of aging: an expanding universe", raised this to twelve.12
- The three hallmarks added in 2023 were disabled macroautophagy (failing cellular recycling), chronic inflammation and dysbiosis (an unbalanced gut microbiome).2
- To qualify as a hallmark, a process must appear with age, accelerate ageing when worsened experimentally, and slow ageing when corrected.2
- The hallmarks are a network: they feed into one another, so a single lever can touch several at once.3
- The framework describes biology in animals and cells. It is not a validated menu of treatments proven to make people live longer.
What the hallmarks of ageing actually are
Ageing looks complicated because it is. Skin, arteries, brain, bone and immune system all decline, seemingly on their own schedules. The value of the hallmarks framework is that it argues these visible declines share a smaller set of underlying cellular causes. If you can name and measure those causes, you can study them, and in principle target them.1
Lopez-Otin and four co-authors, Maria Blasco, Linda Partridge, Manuel Serrano and Guido Kroemer, set three tests for what counts. A genuine hallmark should show up as we age, should speed ageing up if you deliberately worsen it in the lab, and should slow ageing down if you fix it.2 That discipline is what separates this from a loose list of "things that go wrong".
Here, in plain English, are the twelve.
| Hallmark | What it means |
|---|---|
| Genomic instability | DNA accumulates damage and mutations the repair systems no longer fully fix. |
| Telomere attrition | The protective caps on chromosomes shorten with each cell division until cells can no longer divide safely. |
| Epigenetic alterations | The chemical tags that switch genes on and off drift, so the wrong genes are active in the wrong cells. |
| Loss of proteostasis | The quality control that folds and clears proteins falters, so damaged proteins build up. |
| Disabled macroautophagy | The cell's recycling system for clearing worn-out parts becomes sluggish (added in 2023). |
| Deregulated nutrient sensing | The pathways that read food and energy signals (insulin, IGF-1, mTOR) lose their tuning. |
| Mitochondrial dysfunction | The cell's power plants become less efficient and leak more reactive by-products. |
| Cellular senescence | Damaged cells stop dividing but linger, leaking inflammatory signals. |
| Stem cell exhaustion | The reserves that replenish tissues run down, slowing repair. |
| Altered intercellular communication | The hormonal and immune signals between cells become noisy and pro-inflammatory. |
| Chronic inflammation | A persistent, low-grade background of inflammation, often called inflammaging (added in 2023). |
| Dysbiosis | The gut microbiome shifts away from a healthy balance (added in 2023). |
Why they interconnect
The most important idea in the framework is that these are not twelve separate problems on twelve separate tracks. They form a network, and pulling one thread tugs the others.3 The 2013 authors grouped them into three tiers to capture this. Primary hallmarks are the root damage: genomic instability, telomere attrition, epigenetic drift and loss of proteostasis. Antagonistic hallmarks, such as deregulated nutrient sensing, mitochondrial dysfunction and cellular senescence, are responses that help at first but turn harmful when overdriven. Integrative hallmarks, including stem cell exhaustion and altered communication, are what emerges once the damage overwhelms the body's ability to cope.1
A worked example: DNA damage (genomic instability) can push a cell into senescence; senescent cells leak inflammatory signals (chronic inflammation, altered communication); that inflammation stresses neighbouring stem cells (stem cell exhaustion) and disturbs the gut lining (dysbiosis). One root cause radiates outward. This is the basis of the geroscience hypothesis: because ageing is the shared risk factor behind so many chronic diseases, an intervention that nudges the network may, in theory, delay several diseases at once.3 "In theory" is doing real work in that sentence.
Why this matters for reading health news: when a supplement or drug is said to "target a hallmark of ageing", that describes a plausible mechanism, not a proven result. The mechanism is the start of the story, not the end. For how to weigh that kind of claim, see our insights pieces.
Which everyday levers map to which hallmarks
Here is the practical payoff. The lifestyle habits with the strongest human evidence happen to touch many hallmarks at once, which is exactly what the network model predicts. None of this is exotic. It is the unglamorous core of healthy ageing.
| Lever | Hallmarks it plausibly touches | Strength of human evidence |
|---|---|---|
| Regular exercise (aerobic plus resistance) | Telomere attrition, mitochondrial dysfunction, nutrient sensing, senescence, inflammation, stem cell function | Strongest. RCTs link exercise to better telomere maintenance and telomerase activity, and to lower inflammation.45 |
| Adequate sleep | Proteostasis, chronic inflammation, intercellular communication | Good observational and mechanistic data; poor sleep tracks with higher inflammation and older "brain age".6 |
| Diet quality and not over-eating | Nutrient sensing, autophagy, mitochondrial function, dysbiosis, inflammation | Mixed. Calorie restriction reshapes nutrient-sensing pathways; human lifespan benefit is unproven.78 |
| Not smoking | Genomic instability, epigenetic alterations, telomere attrition, inflammation | Strong. Smoking measurably accelerates epigenetic ageing and is one of the clearest modifiable accelerators.9 |
Exercise is the closest thing to a broad-spectrum lever. A 2025 systematic review and meta-analysis of randomised controlled trials found exercise training helped maintain telomere length and significantly raised telomerase activity, the enzyme that protects those caps.4 Reviews mapping exercise onto the hallmarks describe effects on mitochondria, nutrient sensing, senescence and inflammation too.5 If you do one thing, this is the thing. Our start here guide puts it first for a reason.
Sleep connects to proteostasis and inflammation. Deep sleep is when the brain clears metabolic waste, and poor sleep quality is associated with higher systemic inflammation and an older-looking brain in recent cohort work, though this is largely observational.6 Diet acts mainly through nutrient sensing: calorie restriction lowers insulin/IGF-1 and mTOR signalling and switches on autophagy in laboratory studies.7 A meta-analysis of weight-loss trials in adults with obesity found roughly a 15% lower all-cause mortality, but that is weight loss in a specific group, not proof that restriction extends life in everyone.8 Not smoking is the standout for the primary, damage-based hallmarks: current smokers show accelerated epigenetic ageing that partly reverses after quitting.9
Evidence honesty: the hallmarks framework is built mainly on cell and animal studies. For everyday levers, exercise and not smoking have the strongest human data; sleep and diet are supported but lean more on observational and mechanistic evidence. No lifestyle habit, drug or supplement has been shown in a definitive human trial to extend maximum lifespan. The honest claim is improved healthspan, the years lived in good health, not a guaranteed longer life.
How to use this map
Treat the hallmarks as a way to organise your thinking, not a checklist to "fix" one by one. The framework's real lesson is that the boring basics are not boring: they act on multiple hallmarks simultaneously, which is more than any current pill can honestly claim. Use it to ask better questions of the longevity products you see, most of which target a single hallmark in a dish and leap to human marketing. Our wider health library applies this lens across specific compounds, and our stack builder helps you weigh an experimental option against the better-evidenced basics.
Be wary of any supplement or clinic marketed as "targeting the hallmarks of ageing" or "reversing biological age". These phrases borrow the credibility of the science without the evidence. Senolytics, NAD precursors and similar compounds are not licensed by the MHRA as anti-ageing treatments and are not prescribed for ageing on the NHS. Mechanism in a hallmark is not the same as benefit in a person.
- Given my history, which modifiable risks (blood pressure, blood sugar, smoking, weight, activity) should I prioritise first for healthy ageing?
- Are my current symptoms age-related, or signs of a treatable condition worth investigating?
- Do any "biological age" or longevity tests I have seen actually change what you would advise?
- Are there NHS-supported services (smoking cessation, exercise referral, weight management) I could use?
References
- Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. 2013. The Hallmarks of Aging. Cell 153(6):1194-1217. link
- Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. 2023. Hallmarks of aging: an expanding universe. Cell 186(2):243-278. link
- Schmauck-Medina T, et al. 2022. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary. Aging 14(16):6829-6839. link
- Exercise delays aging: evidence from telomeres and telomerase, a systematic review and meta-analysis of randomized controlled trials. 2025. Frontiers in Physiology. link
- Rebelo-Marques A, et al. 2018. Aging Hallmarks: The Benefits of Physical Exercise. Frontiers in Endocrinology. link
- Poor sleep health is associated with older brain age: the role of systemic inflammation. 2025. eBioMedicine. link
- Green CL, Lamming DW, Fontana L. 2022. Molecular mechanisms of dietary restriction promoting health and longevity. Nature Reviews Molecular Cell Biology 23:56-73. link
- Kritchevsky SB, et al. 2015. Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials. PLoS One 10(3):e0121993. link
- Yang Y, et al. 2019. Smoking-Related DNA Methylation is Associated with DNA Methylation Phenotypic Age Acceleration: The Veterans Affairs Normative Aging Study. International Journal of Environmental Research and Public Health. link
This article is educational and does not constitute medical advice, diagnosis, or a treatment recommendation. Medication uses described as “off-label” are not licensed for that purpose in the UK and should only be considered under qualified clinical supervision. Always speak to your GP, pharmacist, or a registered specialist before starting, stopping, or changing any treatment. If you have severe or alarm symptoms - unintentional weight loss, blood in your stool, difficulty swallowing, persistent vomiting, a fever, or severe pain - seek urgent medical care.