The 12 hallmarks of ageing

Each one says what it is in ordinary words, what you can do about it, and how much that is — because for two of them the honest answer today is very little, and nobody else will tell you that.

Genomic instability

The DNA collects typos

Every one of your cells holds the same three-billion-letter instruction book, and has to copy it perfectly, again and again, while sunlight and its own chemistry attack the pages. The proofreaders are astonishingly good. Ageing is what it looks like when the typos start arriving faster than they can be caught.

What you can dolittle you can do today

Less than anyone selling you a pill will admit. What is beyond argument is what causes the damage in the first place: tobacco, sunburn, heavy drinking. After that the useful move is not repair but detection — the scans and blood tests that find the consequence while it is still small.

The science, in one sentence

Damage builds up in the DNA faster than the repair machinery can clear it, and some of it becomes permanent.

In the glossary

No. 39

DNA repairNo. 40

Oxidative stress

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Telomere attrition

The lace ends fray

The ends of your chromosomes are capped, the way a shoelace is capped in plastic. Every time a cell divides the cap gets a little shorter. Run it down far enough and the cell stops dividing altogether — or becomes one of the troublemakers in number eight.

What you can dolittle you can do today

Very little you can buy, and the supplement shelf is a long way ahead of the evidence here. Nothing safely lengthens a human telomere. Smoking, carrying too much weight and years of unrelieved stress all shorten them faster, so the lever is your life rather than a capsule. And longer is not simply better: restarting the machine that lengthens telomeres is one of the tricks a cancer uses to make itself immortal.

The science, in one sentence

The protective caps on the ends of chromosomes shorten with every division; past a point the cell stops dividing or turns senescent.

In the glossary

No. 41

TelomeresNo. 42

Telomerase

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Epigenetic alterations

The instructions get misread

Every cell carries the identical book, and a set of bookmarks tells a liver cell to read the liver chapters and a skin cell to read the skin ones. With the years the bookmarks slide. Cells begin reading pages that were never meant for them, and doing the wrong job in the wrong place.

What you can dosomething you can do

This is where the frontier is loudest, because in animals the bookmarks have been pushed back where they belong. In people it is not a treatment yet, and anybody selling it today is selling ahead of the evidence. What is on the table now is dull and real: sleep, movement and not smoking all track with slower drift when it is measured.

The science, in one sentence

The chemical marks that decide which genes are switched on drift with age, so cells lose the identity of the tissue they belong to.

In the glossary

No. 43

EpigeneticsNo. 44

Partial epigenetic reprogrammingNo. 45

Biological age and the epigenetic clocks

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Loss of proteostasis

Proteins stop folding properly

A protein is a long ribbon that only works once it is folded into one exact shape. Your cells fold millions a minute and throw away the ones that come out wrong. As the folding and the throwing away both get less reliable, the rejects stay where they are, and they clump together.

What you can doa lot you can do

Heat and hard effort both switch on the cell’s own folding crew — a sauna and a proper workout are doing the same job by different routes. And sleep earns more credit than it usually gets: a good deal of the clearing out happens overnight, particularly in the brain.

The science, in one sentence

The systems that fold proteins into shape, and dispose of the ones that fold wrongly, become less reliable, and the rejects clump.

In the glossary

No. 46

Proteostasis

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Disabled macroautophagy

The clean-up crew slows down

Cells eat their own broken parts and build new ones out of the pieces. It is the most efficient recycling scheme in nature, and it runs hardest when nothing is coming in. With age it slows, the rubbish stays where it falls, and a great deal of what ageing feels like from the inside is that pile.

What you can doa lot you can do

This is the one that answers to a decision you make at breakfast. Leave a real gap without food — a shorter eating window, or a longer fast now and then — and the crew goes to work. Hard exercise calls them out too. Coffee, green tea and olive oil each nudge it along. Rapamycin is the strongest trigger we know of, and it is a prescription drug still under study.

The science, in one sentence

The cell’s bulk recycling system, which breaks down its own damaged parts so the material can be reused, becomes less active with age.

In the glossary

No. 47

AutophagyNo. 48

Caloric restriction and fasting

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Deregulated nutrient-sensing

The fuel gauge stops reading true

Your body is always asking one question: is there food about? Insulin, mTOR, AMPK and the sirtuins are how it answers. Answer “plenty” every hour of every day and it never switches out of building mode into maintenance mode. Growth and repair are opposites, and ageing is partly the gauge jammed on full.

What you can doa lot you can do

The most answerable thing on this whole page. Eat inside a shorter window. Keep the refined carbohydrate down. Stay strong and stay lean. Walk after a meal — ten minutes moves this more than most supplements do. Metformin has convincing mouse data and has not yet shown the same in healthy people.

The science, in one sentence

The network that reads how much food is available — insulin, mTOR, AMPK, the sirtuins — stops reporting accurately, so cells keep building when they should be clearing.

In the glossary

No. 49

mTOR and its suppressionNo. 50

AMPKNo. 51

Insulin sensitivityNo. 52

SirtuinsNo. 53

NAD+

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Mitochondrial dysfunction

The power stations falter

Mitochondria are the small engines that turn food and oxygen into the energy every other process on this page runs on. With age there are fewer of them, they leak, and the broken ones are cleared away more slowly. Tiredness that sleep does not fix is often this. So is a good deal of what people mean when they say they feel old.

What you can doa lot you can do

Exercise, and it is not close. It is the only intervention known to build new mitochondria in a living human being: endurance work grows them, interval work does it fastest. Nothing on any shelf comes near it, whatever the label promises.

The science, in one sentence

Mitochondria become fewer, leakier and less efficient, and the damaged ones are cleared away more slowly.

In the glossary

No. 54

MitochondriaNo. 55

PGC-1α

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Cellular senescence

Old cells refuse to leave

A damaged cell has two honourable options: repair itself, or die. A third kind does neither. It stops dividing, refuses to leave, and spends the rest of your life shouting inflammatory signals at the healthy cells around it. A few are useful — that is one way the body stops a damaged cell becoming a tumour. Too many, and the whole tissue ages around them.

What you can dosomething you can do

Exercise clears some of them, which is one more reason it turns up on nearly every entry here. Senolytics — drugs that persuade these cells to finally die — are the most watched idea in the field, and they are in human trials, not on a shelf. Anything sold to you today as a senolytic supplement is running ahead of what has actually been shown.

The science, in one sentence

Damaged cells stop dividing but do not die, and broadcast an inflammatory signal into the tissue around them.

In the glossary

No. 56

Cellular senescenceNo. 57

HormesisNo. 31

Senolytics

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Stem cell exhaustion

The repair pool runs low

Every tissue keeps a reserve of unspecialised cells — apprentices, waiting to replace the workers who wear out. The reserve shrinks over the years, and the ones left answer the call more slowly. It is why a cut closes in three days at sixteen and takes a fortnight at sixty.

What you can dosomething you can do

Nothing you can buy, and clinics offering stem cell injections for ageing are selling well ahead of the evidence. What protects the reserve is unglamorous and free: sleep, enough protein, lifting something heavy twice a week, and not smoking.

The science, in one sentence

The reserve of cells that replaces worn-out tissue shrinks and answers more slowly, so healing slows and tissues thin.

In the glossary

No. 58

Stem cell exhaustionNo. 59

Sarcopenia

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Altered intercellular communication

Cells stop talking properly

A body is an organisation of forty trillion members, and it only works because they keep each other informed — by hormone, by immune signal, by nerve. With age the messages get noisier and the departments stop hearing one another. Each starts optimising for itself, which is exactly how an organisation fails.

What you can dosomething you can do

This is where Kroemer’s point does the work: everything is connected, so improving any other entry on this page improves this one too. Directly, the levers are sleep, daylight early in the day, and keeping the background burn of number eleven down.

The science, in one sentence

The signalling between cells and between organs — hormonal, immune, neuronal — becomes noisier and less coordinated.

In the glossary

No. 60

KlothoNo. 61

Stress, cortisol and the alarm that never switches off

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Chronic inflammation

A fire that never goes out

Inflammation is how a body fights and repairs, and it is meant to flare and then stop. This one never stops: a low, body-wide burn that rises with the years even when there is nothing to fight. It is quiet enough that you cannot feel it and loud enough to damage tissue for decades.

What you can doa lot you can do

Sleep, weight, muscle, oily fish — and the two nobody mentions: look after your gums, and treat a quiet infection rather than living alongside it. This is also the one entry here you can actually watch. An ordinary blood test shows it, which makes it the rare case where you can see whether what you changed worked.

The science, in one sentence

A low, persistent, body-wide inflammatory state that rises with age even without an infection to fight.

In the glossary

No. 62

Chronic inflammation

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Dysbiosis

The gut garden loses variety

A couple of pounds of microbes live in your gut, and they are not passengers. They train your immune system and manufacture compounds your own cells cannot make. A young gut is a garden with forty species in it. An older one is often six, and the weeds are winning — while the wall between the garden and the bloodstream grows leakier.

What you can doa lot you can do

Variety beats any single superfood: thirty different plants across a week does more than any powder. Fibre feeds the good ones, fermented food adds to them. Take antibiotics when you genuinely need them and not when you do not. Probiotic capsules are sold a long way ahead of what the trials actually show.

The science, in one sentence

The gut’s microbial community loses diversity and shifts toward species that provoke inflammation, while the gut wall grows more permeable.

In the glossary

No. 63

The gut microbiome

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