Multiple large studies show that inherited DNA plays only a modest part in determining how long we live.
75–90 % of what determines human lifespan lies outside the DNA we inherit. That “environmental” portion is overwhelmingly shaped by lifestyle: medical care, nutrition, physical activity, smoking, social support, and more.
Scientists have long tried to pin down how strongly our DNA governs the length of our lives. Classic evidence came from a Danish study that followed almost every same-sex twin pair born between 1870 and 1900. By comparing identical twins, who share all their genes, with fraternal twins, who share roughly half, the researchers estimated that genes explained about one quarter of the variation in age at death. Most of the remaining difference came from experiences unique to each individual, such as infections, accidents or personal habits, rather than from upbringing shared within a family.
Newer work suggests that even this 25 percent figure may be generous. A 2018 analysis of hundreds of millions of family links showed that earlier twin results were inflated by “assortative mating”, the tendency to choose partners with similar backgrounds and thus similar survival prospects. After correcting for that bias, the genetic share of lifespan shrank to roughly seven percent. In other words, most of what determines how long we live still lies outside the DNA we inherit.
When researchers scan the genome for specific variants, the list of clear hits remains short. A 2019 meta-analysis that pooled data from twenty international cohorts confirmed that only a handful of DNA changes stand out. The ε4 form of the APOE gene lowers the odds of reaching the longest-lived ten percent of a birth group, while the rarer ε2 form has the opposite effect. A still rarer signal near the GPR78 gene also emerged. Follow-up work in 2025 fine-tuned the APOE story: one tiny change inside the gene, the C version of marker rs7412, appears to be the single strongest genetic brake on extreme old age, whereas two protective variants cluster in populations where people often live longer.
Beyond these common markers, rare, high-impact mutations add another layer. A 2025 study of nearly 400 000 British volunteers found that people who died younger were more likely to carry damaging changes in cancer-related genes such as BRCA1, BRCA2 and TP53. These findings link longevity to the ability to avoid cancer and other age-related diseases.
Taken together, the evidence now paints a consistent picture. Genes do shape lifespan, but their overall weight is modest, well under ten percent in the largest pedigree analysis and perhaps up to a quarter in twin cohorts. The most influential variants act by tilting the risk of major diseases, especially heart, brain and cancer disorders. That leaves lifestyle, medical care and broader social conditions as the dominant levers for adding healthy years.
The heritability of human longevity: a population-based study of 2 872 Danish twin pairs born 1870-1900
This landmark twin study measured how much genes shape lifespan by following almost every same-sex twin pair born in Denmark between 1870 and 1900. By comparing the ages at death of identical and fraternal twins, the team found that genes account for roughly one quarter of the differences in how long people live. Most of the remaining variation came from experiences unique to each individual, not factors shared within a family. The genetic effects were mostly “non-additive,” meaning they arose from special interactions within single genes rather than from many small genetic nudges. In short, DNA matters, but it is far from a life-long destiny.
A meta-analysis of genome-wide association studies identifies multiple longevity genes
Pooling genetic data from 20 cohorts on three continents, researchers compared more than 11 000 people who reached the top ten percent of survival in their birth group with 25 000 typical-lived controls. Only a few DNA changes consistently stood out. The APOE ε4 version was linked to shorter lives, while the rarer ε2 version helped people live longer. A still rarer signal near the GPR78 gene also appeared. The study confirmed that the genetic footprint of long life overlaps with that of major diseases, hinting that genes influence lifespan partly by raising or lowering disease risk.
Bioinformatic and genomic analysis identifies C allele of APOE rs7412 as the most prominent variant limiting extreme human longevity
Using modern data-mining tools on worldwide genomes, scientists singled out one tiny DNA letter, called the C allele of rs7412 in the APOE gene, as the clearest genetic brake on reaching exceptional old age. People who carry this version tend to die earlier than those without it. The analysis also spotted two other APOE-area variants that are more common in regions where people live longer, suggesting that even within a single gene, some forms hinder lifespan while others help. The work refines our picture of APOE, already famous for its role in heart and brain health, as a central player in human ageing.
Rare genetic associations with human lifespan in UK Biobank are enriched for oncogenic genes
Analyzing nearly 400 000 British volunteers, this study looked beyond common DNA tweaks to rare, often damaging mutations. It found that people who died younger were more likely to carry harmful variants in cancer-related genes such as BRCA1, BRCA2 and TP53. Even when common lifespan markers like APOE were considered, these rare hits still mattered. The takeaway is that living a long life may depend as much on avoiding unlucky, high-impact mutations, particularly those that encourage cancer, as on inheriting helpful versions of the usual suspects.
Woman who lived to age 117 had genes keeping her cells “younger”, study shows
Researchers performed the most detailed “multi-omics” analysis ever on a super-centenarian, María Branyas Morera, who lived to 117. Her cells behaved as if they were about 17 years younger than her calendar age, and her gut bacteria looked more like an infant’s than an elder’s. The team linked this youthful biology to a “privileged genome” rich in variants that calm inflammation, support immunity and lower cancer risk. While her healthy lifestyle helped, the findings highlight how exceptionally protective gene combinations can push the limits of human lifespan.
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