DNA changes through several distinct processes, some happening every time your cells divide and others triggered by outside forces like sunlight or chemicals. Every person accumulates an estimated 40 or more new mutations in each cell per year, and parents pass roughly 75 brand-new single-letter changes to each child per generation. These changes range from tiny copying errors to large-scale rearrangements, and your body has elaborate repair systems working constantly to keep most of them in check.
Copying Errors During Cell Division
Every time a cell divides, it copies all 3 billion base pairs of your DNA. The molecular machinery that does this work is remarkably accurate, but not perfect. The main copying enzyme in human cells makes base-pairing mistakes at a rate of roughly 1 error per 10,000 to 100,000 bases before correction kicks in. A built-in proofreading function then catches and fixes about 86% of those errors on the spot, dramatically lowering the final error rate.
After proofreading and additional repair steps, only a tiny fraction of mistakes survive. But “tiny fraction” still adds up across billions of base pairs and trillions of cell divisions over a lifetime. A 2025 study in Nature that tracked mutations across four generations of a single family found an average of 152 new mutations per parent-to-child transmission, including about 75 single-letter changes plus dozens of small insertions, deletions, and structural rearrangements. Around 70 to 80% of those new mutations came from the father’s side, and the number increased with the father’s age at conception.
UV Light and Chemical Damage
External forces physically alter the structure of DNA in ways that go beyond simple copying mistakes. Ultraviolet radiation from sunlight is one of the most common culprits. UV energy breaks a chemical bond within thymine bases (one of DNA’s four letters) and fuses two neighboring thymines together into an abnormal structure called a thymine dimer. This dimer distorts the shape of the DNA helix, blocking the copying machinery and potentially causing the wrong letter to be inserted when the cell tries to read past the damage.
Thymine-thymine dimers are the most common UV photoproduct, but UV also creates thymine-cytosine fusions and other lesion types. If these aren’t repaired before the cell divides, they become permanent mutations, which is why cumulative sun exposure is so tightly linked to skin cancer.
Reactive oxygen species, produced as normal byproducts of metabolism and also generated by pollution, cigarette smoke, and radiation, attack DNA in a different way. They chemically modify guanine (another DNA letter) into an altered form called 8-oxoguanine, which mispairs during copying and can turn a G into a T in the next generation of cells. Oxygen damage also creates breaks in the DNA backbone and sites where a base is lost entirely. Your cells sustain tens of thousands of these oxidative hits per day, most of which are repaired before they cause lasting harm.
How Your Body Repairs Damaged DNA
Cells run multiple overlapping repair systems, each specialized for a different type of damage. For bulky distortions like UV-induced dimers, a process called nucleotide excision repair scans the DNA helix for abnormal shapes. Sensor proteins detect the kink, then a team of enzymes unwinds a roughly 30-letter bubble around the lesion, cuts out the damaged segment, fills in the gap using the undamaged strand as a template, and seals the backbone. In young skin, UV dimers are cleared within about four days. In older adults, the same repair can take one to two weeks.
For oxidative damage and small base modifications, a separate system snips out the single damaged letter and replaces it. Double-strand breaks, the most dangerous type of DNA damage, are handled by yet another pathway that rejoins the broken ends. This rejoining process is less precise and sometimes introduces small insertions or deletions at the repair site.
Epigenetic Changes: Same Sequence, Different Behavior
Not all meaningful changes to DNA involve altering the actual letter sequence. Epigenetic modifications change how genes are read without rewriting the code itself. The most studied mechanism is DNA methylation, where a small chemical tag (a methyl group) is attached to cytosine bases, typically at spots where C sits next to G. This tag can block the proteins that switch genes on, effectively silencing them. Methylation patterns shift throughout life in response to diet, stress, toxin exposure, and aging.
A related process modifies the histone proteins that DNA wraps around. When histones gain acetyl groups, their grip on DNA loosens, making nearby genes more accessible and more likely to be active. When those acetyl groups are removed, the DNA coils tighter and gene activity drops. These histone changes and methylation patterns can persist through cell divisions, giving cells a form of memory. A liver cell and a neuron carry identical DNA but read entirely different sets of genes, largely because of epigenetic marks established during development.
How Mutations Accumulate With Age
DNA repair systems don’t stay equally effective forever. A large study of 135 people between ages 20 and 60 found that the ability to repair UV damage declined by about 0.63% per year, amounting to roughly a 25% drop over four decades. The system that fixes double-strand breaks becomes up to 4.5 times less efficient in aging cells, partly because levels of key repair proteins fall by about 50% in old cells compared to young ones. Mismatch repair and oxidative damage repair also decline with age.
The result is a steady buildup of somatic mutations (changes in non-reproductive cells) over a lifetime. Cancer genome data shows that tumors from patients under 20 carry a median of 0.37 mutations per million bases, while tumors from patients over 80 carry 2.21 mutations per million bases, a six-fold increase. Mathematical modeling suggests that half or more of the mutations found in tumors actually arose in normal, healthy cells before any cancer began, simply through the routine accumulation of errors during aging. This makes somatic mutation buildup one of the central reasons cancer risk rises so sharply with age.
Telomere Shortening
Telomeres are repetitive DNA sequences that cap the ends of chromosomes, functioning like the plastic tips on shoelaces. Each time a cell divides, the copying machinery can’t fully replicate the very end of the DNA strand, so telomeres lose between 50 and 200 base pairs per division. This progressive shortening acts as a biological countdown. When telomeres become critically short, the cell either stops dividing or self-destructs. Telomere length is often discussed as a marker of biological aging, though the rate of loss varies significantly between tissues and individuals.
Intentional DNA Editing With CRISPR
Humans can now change DNA on purpose using gene-editing tools. The most widely known, CRISPR-Cas9, works by guiding a cutting protein to a precise location in the genome and making a double-strand break. The cell then repairs the break using one of two natural pathways. The faster, less precise pathway simply joins the broken ends back together, often introducing small insertions or deletions (typically under 20 base pairs) that can disable a gene. The slower, more precise pathway uses a supplied DNA template to write in a specific new sequence, allowing researchers to correct a mutation or insert new genetic information.
One complication is that the repair process can sometimes produce unexpectedly large deletions or complex rearrangements at the cut site, including changes that involve the partner chromosome. These unintended outcomes are an active area of concern for therapeutic applications, where precision matters enormously.
Germline vs. Somatic Changes
A critical distinction is where in the body a DNA change occurs. Somatic mutations happen in ordinary body cells and affect only the person who carries them. They accumulate throughout life, drive aging, and can lead to cancer, but they aren’t inherited. Germline mutations occur in eggs or sperm and are passed to the next generation, becoming part of every cell in the offspring’s body. The roughly 75 new single-letter variants each parent contributes per generation are the raw material of evolution, occasionally introducing traits that help or harm, but most often landing in stretches of DNA with no obvious effect.