Why Do Some People Live Past 100? What Centenarian DNA Is Revealing About The Genetics Of Longevity

In 2023, scientists at the University of Rochester did something that sounds more like science fiction than biology. They took a single gene from a naked mole rat — an animal that lives for up to 41 years, almost never develops cancer, and seems to age in slow motion compared to every other rodent on Earth — and introduced it into ordinary laboratory mice. The mice lived longer. They got sick less often. Their guts stayed healthier. Their tumours were fewer and smaller.

One gene. Moved from one species to another. And something fundamental about how the recipient animal aged actually changed.

The result, published in the journal Nature and widely revisited in May 2026 as follow-up research accelerated, was not just remarkable in itself. It was proof of a principle that longevity researchers had long suspected but never demonstrated so cleanly: that the genetic mechanisms behind exceptional lifespan are not locked permanently inside the animals that evolved them. They can, at least in some cases, be transferred. And if they can be transferred between species, the question of whether they can eventually be harnessed for human benefit stops being theoretical.

We are living through an extraordinary period in the science of aging. The genetic study of centenarians — people who reach 100 years old — and supercentenarians — those who reach 110 and beyond — has accelerated dramatically with the falling cost of whole-genome sequencing. What researchers are finding is both scientifically precise and philosophically vertiginous: that longevity is not simply the absence of bad luck, and not simply the result of a healthy lifestyle. It has a genetic architecture. It can be studied. And it is beginning, slowly, to be understood.

What Makes a Centenarian Genetically Different?

The first question anyone asks when confronted with someone who has reached 100 years old is almost always the wrong one. What did they eat? Did they exercise? Did they drink? The answers are rarely consistent enough to explain the phenomenon. There are centenarians who smoked for decades. There are centenarians who ate red meat daily and drank wine every evening. There are centenarians who never exercised in any formal sense. The lifestyle factors that predict healthy aging in a population do not reliably explain exceptional longevity at the individual level.

What does predict it, with reasonable consistency, is family history. According to research from Stuart Kim, a professor at Stanford University who has spent years studying longevity genetics, “there’s a reasonably strong genetic component to becoming a centenarian, and we want to find out what that is.” Studies of identical twins suggest that roughly 25 to 30 percent of the variation in human lifespan is attributable to genetic factors — but that percentage rises significantly for those who live past 90 or 100, where the genetic signal becomes stronger and more specific.

The New England Centenarian Study at Boston University Medical Center, one of the longest-running centenarian research programmes in the world, has identified genetic signatures in centenarians that differ systematically from the general population. Centenarians do not simply lack the gene variants associated with disease — they appear to carry specific protective variants that actively buffer against the damage that accumulates with age. The distinction matters: it is not just the absence of vulnerability but the presence of protection.

A 2025-2026 analysis of the genomes of 21 supercentenarians aged between 106 and 117 years, published through PMC, identified 754,520 single nucleotide polymorphisms — SNPs, single-letter variations in the DNA sequence — common across all 21 individuals. These shared variants clustered in specific biological pathways: immune function, inflammation regulation, DNA repair, and cellular stress response. The picture that emerges is not of people who happened to avoid disease but of people whose biology is actively, continuously, and specifically good at handling the insults that aging inflicts on all of us.

The Longevity Gene Found in People Who Live Past 100

Among the most compelling recent discoveries in centenarian genetics is a gene called LAV-BPIFB4 — the Longevity Associated Variant of the BPIFB4 gene. This variant is found at significantly higher frequencies in centenarians and supercentenarians than in the general population, and its effects on biology appear to be broadly protective in ways that are only beginning to be understood.

In a study published on September 29, 2025 in Signal Transduction and Targeted Therapy — a Nature portfolio journal — researchers Yan Qiu, Monica Cattaneo, Anna Maciag, Annibale A. Puca, and Paolo Madeddu, working across the Bristol Heart Institute at the University of Bristol and IRCCS MultiMedica in Italy, demonstrated that a single injection of LAV-BPIFB4 into animal models of progeria significantly improved cardiac function.

According to the peer-reviewed paper, mice received a single intraperitoneal injection of LAV-BPIFB4 delivered via an adeno-associated viral vector, which enhanced cardiac BPIFB4 protein expression 2.5-fold and significantly reduced age-related decline in left ventricular diastolic function. Histological analysis confirmed decreased perivascular fibrosis, an increased number of coronary arterioles, and a measurable reduction in cardiac cells expressing p16 and p21 — the standard molecular markers of cellular senescence.

Progeria is caused by a mutation that produces a toxic protein called progerin, which disrupts the structure of the cell nucleus and drives accelerated aging. The longevity gene did not eliminate progerin. It did not correct the underlying mutation. What it appeared to do was make cells more resilient to progerin’s toxic effects — fortifying the cell against damage rather than removing its source. According to the researchers, this suggests that the gene helps cells withstand the effects of aging insults rather than prevent them from occurring — a distinction that has significant implications for how longevity therapies might be designed.

This connects directly to the biology we explored in our article on telomeres and cellular aging: the accumulation of senescent cells — cells that have stopped dividing but refuse to die, releasing inflammatory signals that damage surrounding tissue — is one of the central mechanisms of aging. LAV-BPIFB4 reduces the burden of these senescent cells in heart tissue, complementing the senolytic drug approach of clearing them directly.

The Naked Mole Rat: Nature’s Most Instructive Anomaly

To understand why the University of Rochester’s gene transfer experiment matters so much, you need to understand just how extraordinary the naked mole rat actually is.

Naked mole rats are mouse-sized rodents native to East Africa. They are, by conventional mammalian standards, bizarre. They are nearly hairless. They are eusocial — like ants or bees, living in colonies with a single breeding queen and a caste of non-reproducing workers. They cannot thermoregulate — their body temperature drifts with their environment, like a reptile. And they are, by a very large margin, the longest-lived rodents known to science.

A typical mouse lives for two to three years. A naked mole rat regularly lives for 30 years, with some individuals reaching 41 years — nearly ten times the expected lifespan of a comparable rodent. More importantly, they do not age in the way other mammals do. Their risk of death does not increase with age. A 30-year-old naked mole rat is not measurably more likely to die than a 5-year-old one — a property called negligible senescence that appears to be unique among mammals. They almost never develop cancer. They show few signs of cardiovascular disease, neurodegeneration, or arthritis.

Vera Gorbunova and Andrei Seluanov at the University of Rochester have spent decades studying what makes naked mole rats so resistant to aging and disease. One of their key findings has been the role of high molecular weight hyaluronic acid — HMW-HA — a large, protective molecule that naked mole rats produce in unusually high quantities. HMW-HA appears to protect cells from cancer-causing changes, regulate immune function, and reduce the chronic inflammation that drives much of aging’s damage. Naked mole rats produce a particularly large and stable form of HMW-HA, encoded by a specific version of the gene HAS2 — hyaluronan synthase 2.

The full study, led by Zhihui Zhang and twelve co-authors including Steve Horvath — creator of the Horvath epigenetic clock — was published in Nature in August 2023 under the title “Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice.” According to the peer-reviewed paper, transgenic mice overexpressing the naked mole-rat Has2 gene showed elevated hyaluronan levels across multiple tissues, a markedly lower incidence of both spontaneous and chemically induced cancer, extended lifespan, and improved healthspan.

The mice’s gene expression patterns — their transcriptome signature — shifted measurably toward that of longer-lived species. The most significant change the researchers observed was attenuated inflammation across multiple tissues, achieved through several distinct pathways: a direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier integrity during ageing.

This 2023 paper built directly on earlier foundational work by the same Rochester laboratory. A 2020 study published in Nature Communications first demonstrated that the very-high-molecular-mass hyaluronan produced by naked mole rats has superior cytoprotective properties compared to the hyaluronan produced by mice and humans — protecting cells from stress-induced cell-cycle arrest and death through the CD44 receptor pathway. That discovery established the molecular foundation that made the subsequent gene-transfer experiment possible.

When Gorbunova’s team introduced the naked mole rat version of HAS2 into mice, the effects were measurable and meaningful. The mice with the transferred gene showed a 4.4 percent increase in median lifespan — equivalent, the researchers note, to an additional three and a half years of human life if the effect scaled proportionally. They were significantly more resistant to spontaneous tumours and chemically induced skin cancer. Their gut tissue stayed healthier with age. Their levels of age-related inflammation were lower.

According to Gorbunova: “Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.” The team’s stated next goal is to transfer this benefit to humans — either by slowing the degradation of HMW-HA or by enhancing its synthesis. They have already identified candidate molecules and are testing them in pre-clinical trials.

The Immune System as the Hidden Architecture of Longevity

One of the most consistent findings across centenarian genetic studies is the outsized role of the immune system. This might seem counterintuitive — we tend to think of aging as something that happens to cells and organs, not to the immune system primarily. But the evidence from centenarian genomes tells a different story.

Research on whole-genome sequencing of Chinese centenarians identified immune-related pathways as the most significantly enriched in the centenarian genome, with specific HLA subtypes — variants of the immune recognition system that determines how the body identifies and responds to pathogens and damaged cells — overrepresented compared to the general population. A separate study confirmed that centenarians possess a unique form of immunity that helps them achieve exceptional longevity, characterised by an immune system that remains active and balanced rather than declining into the chronic low-grade inflammation — inflammaging — that characterises aging in most people.

This immune advantage may operate through multiple mechanisms simultaneously. Centenarians appear better at clearing senescent cells — the zombie cells discussed in our coverage of senolytics — because their immune surveillance remains effective longer. They appear better at controlling chronic infections that drive chronic inflammation. And they appear to carry genetic variants that modulate the inflammatory response itself, preventing it from becoming the self-destructive chronic condition that underlies cardiovascular disease, neurodegeneration, and cancer in the general aging population.

According to research from the supercentenarian SNP study, the shared genetic variants found across individuals aged 106 to 117 clustered heavily in genes associated with immune regulation and cellular stress response — exactly the pathways you would expect to see enriched in people whose biology has successfully managed the accumulated damage of a century or more of living.

Blood Aging and the DNA Barcodes Written Into Your Cells

In May 2025, a study added a new and striking dimension to the genetics of aging. Researchers showed that as blood ages, the diverse ecosystem of stem cells that continuously replenishes the blood system — producing new red blood cells, white blood cells, and platelets — gradually loses its diversity. A small number of stem cell clones out-compete their neighbours and gradually take over blood production. The loss of this diversity, the researchers found, is itself a driver of immune dysfunction and increased disease risk in older age.

The mechanism involves what the researchers described as “barcodes written into DNA” — somatic mutations, accumulated during normal cell division throughout life, that allow individual stem cell lineages to be tracked. In young people, blood production is distributed across thousands of diverse stem cell clones. In old people, it is increasingly dominated by a handful. This consolidation is measurable and progressive, and it correlates with the immune dysfunction that makes older people more vulnerable to infection, cancer, and inflammatory disease.

What is particularly interesting from a longevity genetics perspective is that centenarians appear to maintain greater stem cell diversity in their blood for longer than average. Their immune system’s diversity — and therefore its resilience — remains more intact into extreme old age. Whether this is a cause or a consequence of their longevity, or both, is a question current research is actively investigating.

The connection to epigenetic aging is direct and important here. The epigenetic clock — particularly the Horvath clock, which measures biological age from DNA methylation patterns — is one of the most reliable predictors of health and longevity currently available. Centenarians show biological ages on the epigenetic clock that are significantly younger than their chronological age, suggesting that their DNA methylation patterns are maintained more faithfully over time. The question of what genetic factors allow this more accurate epigenetic maintenance is one of the most active in the field.

How Much of Longevity Is Actually in Your Genes?

This is the question that people really want answered, and it deserves a direct and honest response: the answer is complicated, and anyone who gives you a simple number is oversimplifying.

Population studies suggest that genetic factors account for roughly 25 to 30 percent of the variation in human lifespan overall. Environmental factors — diet, exercise, smoking, stress, socioeconomic status, access to healthcare — account for most of the rest. This is why lifestyle matters, and why the advice to eat well, exercise, sleep, and not smoke is genuinely evidence-based even in the context of longevity genetics research.

But the genetic contribution becomes stronger at the extremes. For people who live past 90, then past 100, then past 110, the heritability of that outcome increases substantially. The lifestyle factors that predict whether someone dies at 65 or 75 are less predictive of whether someone reaches 105 or 115. At those extremes, genetics appears to play a dominant role — not by bypassing the damage that aging causes, but by providing biological machinery that handles that damage more efficiently, more persistently, and more completely than the typical human genome.

According to an October 2025 study reviewing life expectancy trends, longevity gains in wealthy nations have slowed dramatically since 1939. The easy gains — reducing child mortality, controlling infectious disease, improving surgical safety — have largely been realised. The gains that remain require engaging with the biology of aging itself. This is precisely why centenarian genetics research has accelerated: it is no longer purely academic. It is the next frontier of medicine.

What the Genetics of Cancer Tells Us About Living Long

One of the most revealing aspects of centenarian biology is what it reveals about cancer — and the relationship between cancer resistance and longevity is more complex than it initially appears.

Most centenarians do not die of cancer. In a population where cancer is the second leading cause of death for most age groups, the near-absence of cancer mortality in centenarians is striking. But they are not simply avoiding cancer through good fortune. Their biology appears to be actively resistant to it through multiple mechanisms: more effective immune surveillance that identifies and eliminates pre-cancerous cells, better DNA repair systems that catch replication errors before they accumulate into driver mutations, and — as the naked mole rat research suggests — higher levels of protective molecules like HMW-HA that suppress tumour formation at the cellular level.

This connects to a point we explored in our article on the genetics of cancer: telomerase, the enzyme that maintains telomere length, is reactivated in 85 to 90 percent of cancer cells, giving them the capacity to divide without limit. Centenarians navigate this tension with unusual success — maintaining telomere function long enough to preserve healthy tissue renewal while keeping telomerase tightly controlled in the cells where unregulated activity would be dangerous. Understanding exactly how their biology manages this balance is one of the key questions that centenarian research is positioned to answer.

What This Research Could Actually Lead To

The practical implications of longevity genetics research are beginning to materialise into therapeutic programmes, though the timeline from discovery to clinical application remains long.

The University of Bristol team working on LAV-BPIFB4 has described their result as opening “a gene therapy approach to mitigate cardiovascular aging.” The initial application — treating progeria — would benefit only a tiny number of children with this rare condition. But the researchers are explicit that the gene’s effects on normal cardiac aging could eventually be relevant to the far larger population of people experiencing age-related heart disease. Clinical trials in humans are a future ambition rather than a current reality, but the mechanistic understanding now exists to design them.

The University of Rochester team’s work on HMW-HA is already at a more advanced stage of translation. They have identified small molecules that slow the degradation of hyaluronic acid and are testing them in pre-clinical trials. The goal, stated explicitly by Vera Gorbunova, is to develop drugs that maintain HMW-HA levels in aging human tissue — effectively mimicking one of the naked mole rat’s core longevity adaptations without requiring gene therapy.

More broadly, the centenarian genome studies are generating a growing catalogue of longevity-associated gene variants — a catalogue that will eventually enable both predictive genomics (identifying individuals with a higher genetic likelihood of healthy aging) and drug target identification (finding the molecular pathways that longevity-associated variants modulate and designing drugs that activate those pathways in people who did not inherit the protective variants).

What Scientists Say

According to Vera Gorbunova of the University of Rochester, whose team has produced some of the most important results in longevity genetics in recent years, the naked mole rat gene transfer experiment demonstrates something that changes how researchers should think about aging biology: “Unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals.” The implication, she and her colleagues have been careful to note, is not that human immortality is around the corner — it is that the biological mechanisms of longevity are not each species’ exclusive property, but shared features of mammalian biology that can be studied, understood, and potentially redirected.

Researchers at the University of Bristol, commenting on the LAV-BPIFB4 findings, noted that the gene’s ability to improve cardiac resilience without correcting the underlying genetic defect in progeria mice suggests a new therapeutic paradigm — one focused not on fixing what is broken but on strengthening what remains. This approach mirrors what centenarian biology appears to do naturally: not preventing the damage of aging entirely, but maintaining enough biological resilience to manage it effectively for an extraordinarily long time.

According to the supercentenarian SNP analysis published through PMC, the shared genetic variants found in people aged 106 to 117 are not randomly distributed across the genome. They cluster in specific functional pathways — immune regulation, inflammation control, DNA damage response, and cellular stress resistance — with a consistency that suggests these pathways are not incidental to exceptional longevity but central to it. The researchers describe these individuals as providing “valuable insights into aging, longevity, and the factors contributing to their remarkable lifespans” — a characterisation that understates what they offer. They are, in a very real sense, the clearest natural experiment in human biology that exists: people whose genome has passed the most stringent possible test of durability.

The Question Underneath the Science

There is a question that sits beneath all of this research that scientists rarely address directly, because it falls outside the scope of a journal paper but not outside the scope of genuine curiosity: what does it mean to understand the genetics of longevity?

Every centenarian alive today was born before the discovery of DNA’s structure. They grew up without antibiotics for most of their childhood, lived through wars and famines and upheavals that shortened countless other lives, and arrived at extreme old age carrying genetic protection they never knew they had. Their longevity is not the result of longevity research — it is the subject of it. They did not choose their genes.

The generation that might choose them — or at least influence them through precision medicine, gene therapy, or targeted drugs — is being born now. What the research described in this article represents is the early mapping of a territory that medicine has never previously had the tools to explore. The genetics of longevity is not the genetics of immortality. It is the genetics of resilience — of cells that repair themselves a little more faithfully, immune systems that stay active a little longer, hearts that handle stress a little more gracefully.

Whether that resilience can be extended to more people, through medicine that borrows from centenarians and naked mole rats what nature has not seen fit to give everyone, is the question that will define the next generation of genetics research.

Frequently Asked Questions

What genes do centenarians have in common?

Genome-wide studies of centenarians and supercentenarians have identified several consistently enriched genetic features. These include variants in the LAV-BPIFB4 gene, associated with cardiovascular protection and reduced cellular aging; HLA subtypes linked to more effective immune surveillance; variants in genes involved in DNA repair and cellular stress response; and polymorphisms associated with reduced chronic inflammation. According to a 2025-2026 analysis of 21 supercentenarians aged 106 to 117, over 750,000 genetic variants were shared across all individuals studied, clustering particularly in immune regulation and inflammation control pathways.

How much of longevity is genetic?

Population studies suggest genetics accounts for roughly 25 to 30 percent of overall lifespan variation, with lifestyle and environmental factors accounting for most of the rest. However, the genetic contribution increases substantially at the extremes of longevity — people who live past 100 show a stronger and more specific genetic signal than the general population. This is why centenarians tend to cluster in families and why having a centenarian parent or sibling significantly increases your own likelihood of reaching extreme old age.

What is the LAV-BPIFB4 longevity gene?

LAV-BPIFB4 stands for Longevity Associated Variant of the BPIFB4 gene. It is found at higher frequencies in centenarians and supercentenarians compared to the general population and has been shown to protect the heart and blood vessels during aging. In a 2025 study published in Signal Transduction and Targeted Therapy, a single injection of this gene reversed cardiac aging markers in animal models of progeria — the rapid-aging genetic disease — suggesting potential applications for treating both rare accelerated-aging conditions and normal cardiovascular aging.

Can longevity genes be transferred between species?

A landmark study published in Nature by researchers at the University of Rochester demonstrated that a longevity gene from naked mole rats — rodents that live up to 41 years and rarely develop cancer — can be transferred to mice, producing measurable health improvements and a 4.4 percent increase in median lifespan. This is the clearest demonstration to date that longevity adaptations evolved in long-lived species are not permanently locked within those species. The researchers are now investigating whether similar benefits can be achieved in humans through drugs that mimic the gene’s effects.

Why do centenarians rarely get cancer?

Centenarians appear to resist cancer through multiple biological mechanisms simultaneously: more effective immune surveillance that identifies pre-cancerous cells before they can proliferate; better DNA repair systems that catch replication errors before they accumulate into driver mutations; higher levels of protective molecules like hyaluronic acid that suppress tumour formation; and genetic variants that maintain tighter control over the cell division machinery. This multifactorial cancer resistance is likely one of the reasons they reach extreme old age — cancer being one of the leading causes of death in the general population from mid-life onward.

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Why Do Some People Live Past 100? What Centenarian DNA Is Revealing About the Genetics of Longevity