Your cells age in 12 known ways, and most fixes have only worked in mice

Key takeaways

• In 2023, five leading aging researchers listed 12 “hallmarks of aging” in the journal Cell, from damaged DNA to worn-out stem cells, and most of the proof comes from lab animals.
• Stem cells in a mouse’s gut pick up about 796 new DNA mutations a year and ours about 47, yet across 16 mammals the end-of-life totals were similar, a clue that long-lived animals guard their DNA better.
• Smoking a pack a day for a year adds an estimated 150 mutations to each lung cell on average, the clearest human proof that a habit speeds one hallmark.
• In a small Mayo Clinic study, three months of interval training raised mitochondrial capacity in the muscles of people 65 to 80 by 69%, more than the 49% seen in young adults.
• Autophagy, the cell’s recycling system, earned a Nobel Prize in 2016, but proof that fasting puts it to work against human aging is still missing.

A lab mouse lives only a few years. In that time, each stem cell lining its gut collects about 796 new DNA mutations a year².

Your gut stem cells collect about 47 a year, roughly one-seventeenth the mouse rate². Yet you and the mouse end up in about the same place.

In 2022, researchers at the Wellcome Sanger Institute in England compared 16 mammals, from mice to giraffes to people. At the end of a typical lifespan, gut stem cells carried an estimated 3,200 mutations on average, and the totals varied only about threefold from species to species²³. Long-lived animals simply pick up damage more slowly.

That doesn’t prove mutations cause aging, and the authors said other explanations are possible³. But it captures how scientists now think about growing old: as damage that builds up inside cells faster than they can fix it.

Aging is the leading risk factor for cancer, diabetes, heart disease and diseases that destroy brain cells, according to a 2025 review in Nature Reviews Drug Discovery¹². It’s also the vocabulary that longevity marketers borrow.

This is a plain-English tour of what goes wrong inside aging cells, what has been shown to change it in people, and what has only worked in mice.

Scientists sorted aging into 12 hallmarks, mostly by studying animals

In January 2023, Carlos López-Otín, Maria Blasco, Linda Partridge, Manuel Serrano and Guido Kroemer updated a famous list in the journal Cell¹. Their 2013 version named nine hallmarks. The new one added three: failing cellular recycling, chronic inflammation and an unhealthy shift in gut microbes¹.

Our article on anti-aging ads explains the tests a process must pass to make the list. What matters here is where the proof comes from. In 2013, most evidence that fixing a hallmark slows aging came from lab creatures that aren’t mammals. Now experiments in mice, and sometimes monkeys, back most of them¹.

People are the thinnest layer of proof.

The hallmarks also feed each other. Push one up or down in an experiment, and others usually move too¹. Think of an old house, where a leaky roof rots the beams, and the sagging beams crack the walls.

To make the list easier to follow, we’ve sorted it into three groups of our own, not the authors’:

• Damage to the instructions: DNA typos, worn chromosome tips and drifting gene switches.
• Breakdowns in upkeep: misfolded proteins, slow recycling, confused fuel sensors and tired power plants.
• Failures of teamwork: lingering damaged cells, dwindling stem cells, garbled signals, inflammation and gut microbes out of balance.

Your DNA collects typos, and smoking adds them fast

DNA is each cell’s instruction manual. It gets damaged from outside, by chemicals, radiation and germs, and from inside, by copying mistakes, oxidation and slow chemical breakdown¹.

Normal cells collect these typos all their lives. Cells lining the esophagus in young people already carry hundreds of mutations, and by middle age some carry more than 2,000¹. Most do no harm. A few can start a cancer.

Smoking is the clearest proof that a habit speeds this hallmark in people. In a 2016 study in the journal Science, led by the Sanger Institute and Los Alamos National Laboratory, researchers studied more than 5,000 tumors from smokers and people who never smoked⁴.

They estimated that a pack a day for a year adds, on average, about 150 mutations to each lung cell⁴. The figures for other organs were lower: 97 in the voice box, 39 in the throat, 23 in the mouth, 18 in the bladder and 6 in the liver⁴.

One kind of damage builds at a steady, clock-like pace, and smoking seemed to make that clock run fast⁴⁵. These numbers are averages worked backward from tumors, not direct counts in each person⁴⁵.

The hopeful part: Cancer Research UK notes that quitting in middle age removes most of the later lung cancer risk⁵. Our guide to quitting tobacco covers how.

Telomeres are the protective caps on chromosome ends, like the plastic tips on shoelaces. They shorten during normal aging in people and mice¹. People born with faulty telomere upkeep can develop lung scarring, bone marrow failure and a rare condition called dyskeratosis congenita¹.

Telomere tests and pills sold to lengthen telomeres are covered in our articles on biological age tests and anti-aging ads.

Epigenetic changes are shifts in the chemical switches that turn genes on and off. They drift with age, and “aging clocks” measure that drift. The 2023 review says there’s no definitive evidence yet that the drift itself causes aging¹.

Your cells’ power plants sputter, and exercise can rebuild them

Mitochondria are tiny power plants inside cells. They turn food and oxygen into usable energy, and they work less well with age¹.

If a product promises to “boost” your mitochondria, the 2023 review offers a reality check: there’s no evidence yet that deliberately stressing mitochondria, one idea under study, extends healthy life in humans¹. NAD+ drips are covered in our longevity-clinics guide.

Exercise has better human data, though not much of it. In a study published in 2017 in Cell Metabolism, Mayo Clinic researchers trained 72 adults in two age groups, 18 to 30 and 65 to 80⁷. Groups did high-intensity interval cycling, weight training, or a mix⁷.

After about three months, interval training raised mitochondrial capacity in muscle samples by 49% in the younger group and by 69% in the older group⁷⁸. Older muscle, in other words, may respond even more than young muscle. The interval group pedaled in hard bursts three days a week and walked briskly on a treadmill two more⁸.

Lifting weights was the better way to add muscle and strength. Intervals, meanwhile, helped the body use insulin better, a sign of lower diabetes risk⁷.

The study had limits. One outside expert called the groups quite small, and the findings come from muscle samples rather than the whole body⁸. Senior author Sreekumaran Nair said the goal was to learn how exercise works inside cells, not to write exercise advice⁷.

Another outside expert said the results support earlier research⁸. Because this is one small study, our table rates it promising but early.

A Nobel Prize went to the cell’s recycling crew

On October 3, 2016, Yoshinori Ohsumi won the Nobel Prize in Physiology or Medicine for his work on autophagy⁶. The word comes from Greek and means “self-eating”⁶.

Autophagy is how a cell wraps up worn-out parts and breaks them down for reuse, like a crew that hauls old furniture to a recycling yard. In the early 1990s, Ohsumi starved baker’s yeast that couldn’t digest the waste. Within hours, the vacuole, the yeast cell’s recycling compartment, filled with packets of undigested cell parts, proof the process existed⁶.

He then found the genes that run it. Human cells use similar machinery to get fuel during starvation, destroy invading bacteria and viruses, and clear damaged proteins⁶. The Nobel announcement noted that faulty autophagy has been linked to Parkinson’s disease, type 2 diabetes and other disorders common in older people⁶.

With age, key autophagy genes become less active in human tissues¹. Related trouble shows up in protein upkeep. Misfolded proteins clump inside or outside cells, a feature of Alzheimer’s, Parkinson’s, ALS and cataracts¹.

Does fasting “clean out” your cells?

Online claims say fasting switches on autophagy and slows aging. Starvation did trigger autophagy in Ohsumi’s yeast⁶. Human proof is another matter.

The 2023 review notes that a fasting-linked lifespan boost in flies, which depended on autophagy, had not yet been tested in mammals¹. It adds that diet-restriction trials in people are hard because participants struggle to stick with them¹.

Our article “Intermittent fasting ties ordinary dieting in trials, which can be good news” covers eating schedules. For the risks of long fasts, see “Fasting windows help some people eat less, while long fasts add real risks.”

Repair crews dwindle and signals get garbled

Stem cells are the body’s repair reserve. Muscle relies on satellite cells to heal, and blood stem cells lose some ability to rebuild with age¹. Briefly turning on genes that reset cells to a younger state has rejuvenated tissues in mice. As of 2023, lifespan gains had been shown only in mice bred to age fast¹.

Senescent cells are damaged cells that stop dividing but don’t die. Our companion article on senescence covers them and the drugs being tested to clear them.

Fuel sensors are signaling systems, including insulin and a pathway called mTOR, that tell cells whether food is plentiful. Eating less and fasting extend lifespan in several lab species, including primates, and the drug rapamycin does so in animals even when started late in life¹.

In people, a two-year trial that trimmed calories by about 14% found signs of a more active thymus, the gland that trains immune cells, and calmer inflammation in fat tissue¹. Our article on biological age tests covers calorie-cutting trials and aging clocks.

Inflammation and garbled signals between cells are covered in our article on anti-inflammatory claims, and a later article covers inflammation and aging.

Gut microbes shift with age too. Giving old mice gut bacteria from young mice improved some measures of health¹. In people, one early-stage trial of a single gut bacterium improved metabolic measures in people with obesity or diabetes¹.

The hallmarks in plain words

This table is our own summary. “Rating” uses our four-level scale and refers to human evidence that you can change the process.

Hallmark	What goes wrong	Best human evidence	What seems to affect it	Rating
Genomic instability	DNA typos pile up faster than cells fix them12	A pack a day adds about 150 mutations per lung cell each year4	Not smoking; no proven way to speed repair12	Strong evidence that smoking adds damage
Telomere attrition	Chromosome caps wear down1	Inherited telomere defects cause lung and marrow disease1	No proven product	Not enough evidence for telomere pills
Epigenetic alterations	Gene switches drift1	Small clock shifts in trials (see our biological age article)	Diet and supplements under study	Promising but early
Loss of proteostasis	Proteins misfold and clump1	Clumps mark Alzheimer’s, Parkinson’s and cataract1	Nothing proven	Not enough evidence
Disabled autophagy	Cell recycling slows1	Key genes less active with age1	Fasting, mostly in animals1	Not enough evidence in people
Nutrient sensing	Fuel sensors misread signals1	A two-year, 14% calorie cut revived thymus activity1	Eating less; rapamycin in animals1	Promising but early
Mitochondrial dysfunction	Power plants make less energy1	Interval training raised muscle capacity 69% in a small study of people 65 to 807	Exercise	Promising but early for muscle; not enough evidence it slows overall aging
Cellular senescence	Damaged cells linger and inflame neighbors1	Small drug trials (see our senescence article)	Experimental drugs	Promising but early
Stem cell exhaustion	Repair reserves dwindle1	None in people; reprogramming works in mice1	Nothing proven	Not enough evidence
Signals and inflammation	Cells send garbled, inflamed messages1	See our inflammation articles	Covered there	Rated in those articles
Dysbiosis	Gut microbe mix shifts1	One early-stage trial of a gut bacterium1	Under study	Not enough evidence for aging

Read down the “Best human evidence” column. The clearest entries involve habits, not products: smoking adds DNA damage, interval training rebuilt muscle mitochondria in one study, and eating less nudged a few measures in a two-year trial.

Why mice make promises people can’t keep

Mice are a fast-forward version of aging. Their gut cells collect mutations about 17 times faster than ours², and a whole lifespan study fits into a few years.

That speed is useful, but mouse results have tripped up researchers for decades. A 2008 paper describing the National Institute on Aging’s testing program listed the problems¹⁰. Calorie cutting lengthened life in males of one inbred mouse strain but not another¹⁰. The typical lifespan of the same strain varied by about 22% from lab to lab¹⁰.

So the NIA built its Interventions Testing Program to do it the hard way. Each compound is tested at three sites at once, in male and female mice bred to be genetically mixed, more like a big family of siblings than a set of identical twins⁹. The studies are sized to catch a 10% change in lifespan, and negative results get published too⁹.

Even then, sex can flip a result. The diabetes drug acarbose extended median lifespan by about 22% in male mice but only about 5% in females¹¹.

And a mouse result is still a mouse result. The NIA’s own program page makes no claims about people⁹. A 2025 review adds that it isn’t clear whether lifespan-extending treatments in lab animals hit the root causes of aging or only its downstream effects¹².

Our article “Only 1 in 20 treatments tested in animals wins approval for people” explains the wider pattern, and “Some drugs lengthen mouse lives, but proven prevention still ranks higher” covers the NIA program’s results.

What this science means if you value natural prevention

Natural-health readers often say the body has deep powers of repair. The hallmark research agrees. Cells copy-edit their DNA, recycle their own parts and rebuild power plants when you ask more of them¹⁶⁷.

The research also shows where your choices count most. The two clearest human examples in this article are a habit you can drop and a habit you can build: not smoking and exercise⁴⁷.

Notice what’s missing from that list: capsules. A product that names a hallmark has borrowed a scientific map. It hasn’t proved it reached the destination.

The same skepticism readers bring to drug-company claims fits here. Researchers who patent longevity drugs and companies that sell longevity supplements both have reasons to talk up mouse data. Ask both for the human trial.

Questions readers ask

The bottom line

Aging inside cells is real and measurable: DNA collects typos, chromosome tips wear down, recycling slows and power plants sputter. Scientists have organized these changes into 12 hallmarks, and most of what’s known about slowing them comes from yeast, flies, mice and other lab species.

In people, the clearest evidence points to two everyday choices. Not smoking spares your DNA a heavy load of damage, and in an early study, interval training rebuilt the power plants in older muscle. Treat any product that promises to fix a hallmark as a mouse result until it shows you a human trial.

Related reading

• How to decode “reverse your age” ads that outrun the science
• Biological age tests can disagree with themselves by years
• Only 1 in 20 treatments tested in animals wins approval for people
• Activity tracks with lower risk of 13 cancers, and even one-minute bursts count
• Zombie cells are real, and pills sold to clear them are still unproven

Sources

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2. Cagan A, Baez-Ortega A, et al. “Somatic mutation rates scale with lifespan across mammals.” Nature, 2022;604:517–524. nature.com
3. Wellcome Sanger Institute. “Mutations across animal kingdom shed new light on ageing.” News release, April 13, 2022. sanger.ac.uk
4. Wellcome Sanger Institute. “Smoking a pack a day for a year causes 150 mutations in lung cells” (on Alexandrov LB, et al., Science, 2016). News release, 2016. sanger.ac.uk
5. Cancer Research UK. “Scientists reveal genetic ‘signatures’ left by cigarette smoke.” Cancer News, November 3, 2016. news.cancerresearchuk.org
6. Nobel Assembly at Karolinska Institutet. “The Nobel Prize in Physiology or Medicine 2016” (press release). NobelPrize.org, October 3, 2016. nobelprize.org
7. Cell Press, via ScienceDaily. “How exercise, interval training in particular, helps your mitochondria stave off old age” (on Robinson MM, et al., Cell Metabolism, 2017;25(3):581). ScienceDaily, March 8, 2017. sciencedaily.com
8. Scutti S. “Interval training exercise could be a fountain of youth.” CNN, republished by KSL.com, March 8, 2017. ksl.com
9. National Institute on Aging. “About the ITP.” Interventions Testing Program, Division of Aging Biology, accessed October 2026. nia.nih.gov
10. Nadon NL, Strong R, Miller RA, et al. “Design of aging intervention studies: the NIA interventions testing program.” Age (Dordrecht), 2008;30(4):187–199. pmc.ncbi.nlm.nih.gov
11. National Institute on Aging. “Diabetes drug increases lifespan of male mice, shows smaller effect in females” (on a 2013 study in Aging Cell). NIA news. nia.nih.gov
12. Bujarrabal-Dueso A, Garinis GA, Robbins PD, Vijg J, …, Schumacher B. “Targeting DNA damage in ageing: towards supercharging DNA repair.” Nature Reviews Drug Discovery, 2025;24:785–807. nature.com