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The longevity gene ApoE2 was brought to Europe during the Stone Age.
August 31, 2026
Birgitta Dunckel
How long we live may be more strongly influenced by our genes than previously thought. But there is no single longevity gene. What APOE and FOXO3 reveal about longevity – and the role lifestyle still plays.
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How strongly do our genes determine how long we live? For decades, the answer was: less than many people assumed. Around 20 to 25 percent of differences in lifespan were attributed to genetic factors. But a study published in 2026 in the journal Science calls this rule of thumb into question. According to the study, the genetic influence on biologically determined lifespan could exceed 50 percent.
There is still no single "longevity gene." Rather, it is the interplay of numerous genes that helps determine how we age and which diseases we are susceptible to. Two names come up particularly often in research: APOE and FOXO3. Yet even a favorable genetic profile does not guarantee a long life – and unfavorable genes do not mean our fate is sealed.
The new study argues that earlier calculations may have failed to adequately account for an important factor: people do not die solely from biological aging processes, but also, for example, from accidents or infectious diseases. Such external causes of death can obscure the genetic contribution to lifespan in statistical analyses.
After mathematically accounting for this so-called extrinsic mortality and analyzing data from several twin cohorts, the scientists arrived at a surprising result: the heritability of the "intrinsic" human lifespan could be more than 50 percent.
This does not mean, however, that half of any individual's lifespan is predetermined at birth. Heritability describes variation within a population – and always depends on prevailing environmental conditions as well. Moreover, this is a new methodological approach that challenges earlier estimates without conclusively settling the debate.
The gene APOE (Apolipoprotein E) encodes a protein that plays a central role in fat metabolism – transporting cholesterol, among other things – and also performs important functions in the brain. Every person carries two APOE variants, one inherited from each parent.
Three variants are particularly common: APOE ε2, ε3, and ε4. APOE ε3 is the most frequent and is generally considered neutral with regard to Alzheimer's risk. APOE ε2 is associated with a lower risk of Alzheimer's, while APOE ε4 raises the risk and is linked to an earlier onset of the disease. Even so, APOE ε4 is not an "Alzheimer's gene": many carriers never develop dementia, and Alzheimer's can occur in people without this variant.
APOE also stands out in research on exceptional longevity. APOE ε4 is less common among centenarians, whereas certain APOE ε2 constellations have been positively associated with exceptional longevity. The gene therefore influences disease risk rather than the "aging clock" directly, yet those risks can play a role in determining whether a person reaches a very advanced age.
APOE makes it especially clear why genes and lifestyle cannot be neatly separated. Exercise, not smoking, and maintaining healthy blood pressure and metabolism are generally among the modifiable risk factors for dementia and cardiovascular disease. Whether these measures work differently or more powerfully in people with APOE ε4 than in those without this variant, however, has not yet been clearly established.
A 2025 meta-analysis of randomized exercise studies highlights how inconsistent the data are: depending on the endpoint examined, APOE ε4 carriers sometimes benefited more, and sometimes people without this variant did. The evidence to date is limited. The appealing idea that one can simply "outrun" an unfavorable genetic profile therefore oversimplifies the picture.
Just how much the genetic starting point has shifted over the course of human history is illustrated by research into ancient DNA. A research group led by Professor Almut Nebel of Kiel University examined the evolutionary history of APOE using DNA up to 12,000 years old for a 2023 study published in Aging Cell.study the evolutionary history of APOE using DNA up to 12,000 years old.
The research found that the distribution of APOE variants in Europe changed significantly over time. Between early European hunter-gatherers and the first farmers, the researchers identified differences in allele frequencies that may have been linked to shifts in diet and living conditions. From around 4000 BC onward, their analysis suggests, further changes can be explained primarily by the mixing of different population groups.
The findings illustrate a fundamental principle of longevity research: the effects of a genetic variant cannot be fully understood apart from the living conditions in which a person exists.
Less well known than APOE but equally significant for aging research is FOXO3. Variants of this gene have repeatedly been linked to exceptional longevity across different population groups. FOXO3 is involved in processes such as metabolism, inflammatory responses, the management of oxidative stress, and autophagy – mechanisms that also play a role in biological aging.
A recent 2026 review continues to count FOXO3 among the leading candidates in genetic longevity research. A favorable variant is, however, no guarantee of an exceptionally long life.
The new Science study suggests that genes may matter more to biologically determined lifespan than previously assumed. At the same time, the dramatic rise in average life expectancy within just a few generations demonstrates how powerfully external factors can shape how long we live.
For the individual, the key takeaway is this: we can do little to change our genes, but many important risk factors are within our control. Not smoking, regular exercise, a balanced diet, and the treatment of high blood pressure, elevated blood lipids, and diabetes can all reduce the risk of the many diseases that stand in the way of a long and healthy life.
Commercial genetic tests now promise insights into a wide range of health risks, and your own APOE status can be determined through them. However, such results cannot tell you how long you are likely to live.
Even the gene variants identified so far each account for only a small share of the variation between individuals. So-called polygenic risk scores are also currently unable to reliably predict any one person's lifespan.
An APOE test should therefore not be mistaken for a "longevity test." APOE ε4 provides information about statistical disease risks – particularly for Alzheimer's – but does not predict whether a person will actually develop the disease. For this reason, APOE testing is not routinely used to predict later Alzheimer's dementia in healthy individuals.
Searching for a single longevity gene leads in the wrong direction. While new research suggests that genes may matter more to our biologically determined lifespan than long assumed, APOE, FOXO3, and other variants are only pieces of a complex puzzle. Our genes shape the starting point – but how healthily we age depends on much more than that.
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