Why We Age: What Biology Says About Growing Old
Biologists now list a dozen linked processes behind aging, and a few animals, such as the naked mole-rat, seem to dodge some of them.
Humans age because damage slowly builds up in cells and tissues faster than the body’s repair systems can fix it. In a 2023 review in the journal Cell, a team led by Carlos López-Otín grouped the main causes into 12 “hallmarks of aging,” including DNA damage, shortening telomeres, worn-out proteins and senescent cells that stop dividing but do not die.
None of these is the single cause. They feed into each other, which is one reason aging has been so hard to slow. This is an explainer of the biology, not health advice; questions about your own health belong with a clinician.
What goes wrong inside aging cells?
Every cell takes constant small hits. DNA picks up copying errors and chemical damage. Proteins fold the wrong way or clump together. Mitochondria, the parts of the cell that release energy from food, work less efficiently and leak reactive molecules that cause more damage.
Young bodies repair most of this. They recycle broken proteins, fix DNA and replace lost cells from pools of stem cells. With age the repair work falls behind. Each problem on its own is small, but together they reduce how well tissues recover from stress, injury or infection. That loss of resilience, more than any single failure, is what aging looks like at the level of the body.
What are the hallmarks of aging?
The hallmarks are a framework for sorting aging research, first published in Cell in 2013 with nine items and updated in 2023 with twelve, by the same five authors. To count as a hallmark, a process has to appear with age, make aging speed up when it is made worse in experiments, and slow aging when it is reduced, according to the 2023 paper.
| Hallmark | What it means in plain words |
|---|---|
| Genomic instability | DNA damage and mutations pile up |
| Telomere attrition | Protective caps on chromosome ends get shorter |
| Epigenetic alterations | Chemical tags that switch genes on and off drift |
| Loss of proteostasis | Cells struggle to keep proteins correctly folded |
| Disabled macroautophagy (added 2023) | The cell’s recycling system slows down |
| Deregulated nutrient sensing | Signals about food and growth go out of balance |
| Mitochondrial dysfunction | Energy production becomes less efficient |
| Cellular senescence | Damaged cells stop dividing but linger |
| Stem cell exhaustion | Fewer working stem cells to replace tissue |
| Altered intercellular communication | Signals between cells and organs change |
| Chronic inflammation (added 2023) | Low-level inflammation that does not switch off |
| Dysbiosis (added 2023) | Changes in the microbes living in the gut |
Much of the evidence for these links comes from yeast, worms, flies and mice. The 2013 review pointed out that the rate of aging is controlled, at least partly, by genetic pathways that evolution has kept across very different species, which is why lab animals are useful models.
Why do telomeres get shorter?
Telomeres are repeated stretches of DNA that cap the ends of chromosomes, a bit like the plastic tips on shoelaces. The machinery that copies DNA before a cell divides cannot copy the very end of a chromosome, so telomeres get a little shorter with many divisions.
In 1961, Leonard Hayflick and Paul Moorhead reported that normal human cells grown in the lab divide a limited number of times and then stop, a ceiling now called the Hayflick limit. Short telomeres are one of the signals that trigger this stop. Some cells, such as many stem cells, make an enzyme called telomerase that rebuilds telomeres. Many cancer cells switch it on too, which helps them keep dividing. Our explainer on how DNA works covers chromosomes and copying in more detail.
What are senescent cells?
Senescent cells are cells that have permanently stopped dividing, usually because of damage, but have not died. They are not useless. Stopping division keeps damaged cells from turning cancerous, and senescent cells help with wound healing. The trouble is that they release inflammatory signals, and they become more common with age.
A 2016 study in Nature tested what happens when they are removed. Researchers used genetically engineered mice in which a drug triggered the death of cells carrying a senescence marker called p16Ink4a. Starting at one year of age, the treatment extended median lifespan in male and female mice of two genetic backgrounds, delayed tumors and reduced age-related decline in the kidneys, heart and fat tissue.
That result was in engineered mice, not people. Drugs that aim to clear senescent cells in a similar way are being studied, but results in mice often fail to carry over to humans.
Why do some animals barely age?
A few species do not show the usual rise in death risk with age. In most mammals, the chance of dying in a given year climbs steeply as the animal gets older. The naked mole-rat, a hairless, mouse-sized African rodent, seems to break that rule.
A 2018 analysis in eLife pulled together more than 3,000 lifespan records from captive naked mole-rats. Their risk of dying did not increase with age, even at ages 25 times past the age when they can first breed, and survival analysis showed a substantial share of the population reaching 30 years. The authors described it as a non-aging mammal, though the data come from well-protected captive colonies.
Hydra, tiny freshwater relatives of jellyfish, go further. A 2015 study in PNAS followed 2,256 hydra in two labs for more than 3.9 million animal-days and found extremely low, constant death rates and no steady decline in reproduction with age. Hydra are made largely of stem cells that keep renewing the body, which may explain it. Their life expectancy in the wild is far shorter, so the lab result shows how long their bodies can keep going, not how long a typical hydra lives. We cover other record holders in the longest-living animals.
Bottom line
Aging comes from many kinds of damage that build up as repair slows: DNA errors, shorter telomeres, misfolded proteins, failing mitochondria, lingering senescent cells and chronic inflammation, grouped into 12 hallmarks in a 2023 Cell review. Removing senescent cells extended median lifespan in engineered mice, and naked mole-rats and hydra show that aging is not the same in every species. Turning those findings into anything that slows human aging remains unproven.
FAQ
Is there a single gene that controls aging?
No single gene controls aging in people. Studies in worms, flies and mice have found genes that change lifespan when altered, but human aging involves many linked processes.
Do telomeres decide how long a person lives?
Telomere shortening is one of the 12 hallmarks, not a countdown clock on its own. It interacts with DNA damage, senescence and other processes, and lifespan depends on all of them plus genes, environment and chance.
Can anything reverse aging?
Some treatments have extended lifespan or reversed specific signs of aging in lab animals. No treatment has been shown to reverse aging in people, and anyone considering a product sold for that purpose should talk to a clinician first.
Why is the naked mole-rat studied so much?
Naked mole-rats live more than 30 years, far longer than other rodents their size, and in captivity their risk of death does not rise with age. Researchers study their cells to learn how they resist age-related damage.
