Jeanne Calment of France died in 1997 at the age of 122 years and 164 days, a record verified by Guinness World Records that has stood unbroken for nearly three decades. For most of that time, researchers treated her lifespan not just as a statistical outlier but as something close to an immovable ceiling – evidence that the human body, regardless of circumstance, simply runs out of road around that age. A study published this month in a leading scientific journal suggests that ceiling is not where anyone thought it was. The reasons why are written in the DNA of cells that never learned to replace themselves.
The question the researchers asked was precise: if every reversible process driving human aging were somehow eliminated – every case of cellular senescence, every instance of mitochondrial breakdown, every episode of inflammation – what would ultimately kill us? Their answer, built from a computational model rather than a clinical trial, points to something far more fundamental. Random copying errors in DNA, accumulating silently inside cells over a lifetime, appear to impose a hard biological limit on how long any human being can survive. The only dispute is where exactly that limit sits.
Researchers from the Skolkovo Institute of Science and Technology in Russia, working with co-authors from the AI Research Institute (AIRI), have for the first time quantitatively assessed how somatic mutations – random DNA changes that accumulate in cells with age – limit the maximum human lifespan. Their findings, which push directly into the debate over human lifespan extension, carry significant implications for how medical science should prioritize its most ambitious interventions.
What the Model Found
Somatic mutations accumulate with age and can cause cell death, though their exact quantitative contribution to limiting human lifespan had previously remained unclear. The Skoltech team developed an incremental modeling framework that progressively incorporates factors contributing to aging into a model of population survival dynamics, using it to estimate lifespan limits if all aging hallmarks were eliminated except somatic mutations. Their analysis reveals a fundamental asymmetry across organs: post-mitotic cells such as neurons and cardiomyocytes act as critical longevity bottlenecks, with somatic mutations reducing median lifespan from a theoretical non-aging baseline of 1,759 years to 156 years, while proliferating tissues like the liver maintain functionality for thousands of years through cellular replacement, effectively neutralizing mutation-driven decline. Multi-organ integration predicts median lifespans of 146 to 194 years – approximately twice current human longevity.
The findings are based on computational modeling rather than experimental evidence and do not suggest humans are close to reaching such ages. They do, however, offer the first mathematically grounded framework for understanding which biological mechanisms are responsible for the gap between how long we live and how long we theoretically could.
The Biological Architecture of Aging
To understand what the Skoltech model reveals, it helps to understand what aging researchers already know about why the body deteriorates. The current scientific consensus identifies twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks, codified in a landmark 2023 review published in Cell, are grouped into primary, antagonistic, and integrative categories based on how they initiate and amplify each other.
The interdependence of aging hallmarks means that the experimental accentuation or attenuation of one specific hallmark usually affects other hallmarks as well. This interconnectedness is one reason why targeting aging has proven so difficult: interventions in one system tend to create downstream effects in others, making it nearly impossible to isolate and neutralize a single driver.
The Role of DNA Damage
Among all twelve hallmarks, genomic instability – the progressive accumulation of DNA damage – sits at the top of the causal hierarchy. The Skoltech research, published in npj Aging, uses a multistage model to “switch on” aging mechanisms one by one and measure how long a human could live if all but somatic mutations – a DNA change that arises in any non-reproductive cell after conception, meaning it affects the body’s tissues but cannot be passed to offspring – were cured.
Somatic mutations are random changes in DNA that occur in the body’s cells throughout life. Unlike germline mutations, they are not inherited, but they gradually accumulate with age and can damage cells, impair their function, and contribute to the development of age-related diseases. Every time a cell divides, copying errors have a chance to occur. Environmental stressors – ultraviolet radiation, chemical exposures, metabolic byproducts – add further insults. Over decades, these errors stack up.
The model assumes somatic mutations accumulate throughout life and estimates how much they contribute to declining survival, independent of other hallmarks of aging. By modeling somatic mutations as the sole remaining driver of mortality in an otherwise “cured” human population, the researchers could calculate what those mutations alone cost us in years.
Mitochondria and the Compounding Problem
Somatic mutations do not act in a vacuum. Mitochondrial dysfunction is regarded as one of the foremost determinants in driving aging, according to a 2025 review published in Signal Transduction and Targeted Therapy. Mitochondria – the organelles that generate the energy cells need to function – accumulate their own mutations over time, separate from nuclear DNA damage, and this dual burden accelerates cellular deterioration. In post-mitotic cells, where there is no mechanism to dilute defective mitochondria through cell division, this damage simply compounds.
The Organ-by-Organ Asymmetry
The 2026 Skoltech study’s sharpest finding is the difference between how different tissues handle somatic mutations – and what that difference means for the organs that ultimately limit how long we live.
Tissues That Can Renew Themselves
Proliferating tissues like the liver maintain functionality for thousands of years through cellular replacement, effectively neutralizing mutation-driven decline. When a liver cell accumulates too many mutations to function properly, the body replaces it. The regenerated cell starts with a relatively clean genetic slate. As long as the stem cell pool supplying new liver cells remains intact and functional, the organ can sustain itself almost indefinitely on a biological timescale.
This implies that protecting the liver from somatic mutations, in a world where every other aging mechanism has been eliminated, would deliver essentially no additional lifespan benefit – that organ is already capable of outlasting any realistic human lifespan.
The Bottleneck Organs: Brain and Heart
Neurons and cardiomyocytes – the muscle cells of the heart – cannot replicate to replace themselves. A neuron lost in early adulthood is, with very limited exceptions, a neuron lost forever. Post-mitotic cells such as neurons and cardiomyocytes act as critical longevity bottlenecks, with somatic mutations reducing median lifespan from a theoretical non-aging baseline of 1,759 years to 156 years.
Their model found that somatic mutations remain the principal limiting factor in these long-lived tissues, and those mutations are especially difficult to overcome because they build up in neurons and heart muscle cells that cannot readily be replaced.
Cardiomyocyte somatic mutations accumulate with age at rates faster than in many dividing cell types and non-dividing neurons, according to a 2022 study published in Frontiers in Aging. The heart, it turns out, is genetically deteriorating faster than the brain – which itself deteriorates faster than the liver.
The public health consequences of this biological asymmetry are already visible in mortality statistics. As Dr. Jordan Weiss, an Assistant Professor in the Division of Precision Medicine and Optimal Aging Institute at NYU Grossman School of Medicine, told Newsweek: “The conditions that cost people their independent, healthy years – such as dementia and heart failure – fall heavily on precisely the tissues that cannot regenerate. So the gap between how long people live and how long they stay well is not one general breakdown of the body. It is concentrated in the organs that have no way to replace worn-out cells.”
There were 55.2 million people worldwide living with dementia in 2019, and the number was estimated to increase to 78 million by 2030, according to data published in the Journal of the American Heart Association. The study argues that even if scientists were able to slow or eliminate most known hallmarks of aging, the accumulation of DNA mutations in critical tissues would remain a decisive constraint on outcomes for precisely those patients.
The Modeling Framework: How the Research Was Conducted
The current study represents the first step of a broader research agenda: isolating somatic mutations as a single variable and measuring their effect on population survival curves with all other aging mechanisms switched off. The authors plan to incorporate other hallmarks of aging into the model – mitochondrial dysfunction, loss of proteostasis, telomere shortening, and epigenetic changes – to build a comprehensive quantitative theory of human aging.
The work was a thought experiment designed to estimate the upper limit that somatic mutations alone might impose on human lifespan, not a prediction of how long people will live in the future. The researchers built a mathematical model that systematically quantified how the DNA mutation rate impacts the body’s major organs and used this to calculate the lifespan of a human population free of age-related disease.
As lead author Dmitrii Kriukov, a computational biologist at Skoltech and AIRI, noted: “Our study shows that somatic mutations contribute significantly to aging, but they cannot by themselves explain the observed mortality.” The implication is that the 156-year figure represents not a prediction but a theoretical ceiling – the outer boundary imposed by one specific mechanism, holding all others constant.
Read More: Could Humans Really Live to 150? Here’s What Scientists Actually Found
Therapeutic Implications: Where the Science Points Next
The organ-level asymmetry revealed by the model has direct implications for how longevity medicine should allocate its attention and resources. If liver cells can already self-renew across timescales that dwarf any plausible human lifespan, then interventions designed to protect hepatic DNA are of limited therapeutic value for extending maximum lifespan. The harder problem – and the one the model identifies as most consequential – is the brain and heart.
As Michael Leone, Assistant Professor in the Division of Precision Medicine at NYU Grossman School of Medicine, told Newsweek: “Somatic mutations are likely among the highest-hanging fruit in targetable geroscience” and that lower-hanging targets, “such as inhibiting mTOR with rapamycin or clearing senescent cells, are far more logical interventions to prioritize.”
Senolytic therapies – treatments designed to eliminate the senescent cells that accumulate in aging tissues and drive inflammation – have attracted considerable attention from both academic researchers and the biotechnology industry. The Skoltech model suggests those approaches, while valuable for healthspan (the number of years a person lives in good health), may not push the ceiling on maximum lifespan in the way that targeting neuronal and cardiac DNA integrity could.
The distinction between healthspan and lifespan is a practical one. Dr. Jordan Weiss’s research at NYU Grossman School of Medicine addresses precisely this gap, aiming to understand why some people stay healthy as they age while others do not, and to solve for the gap between healthspan and lifespan by identifying how key exposures over the life course shape trajectories of health and well-being. The Skoltech study provides his work – and the field broadly – with a more precise biological map of where that gap originates.
Limitations and Scientific Context
The Skoltech findings demand careful framing. The results are based on computational modeling rather than experimental evidence and do not suggest humans are close to reaching such ages. No human has ever approached 156 years. The current verified record, held by Jeanne Calment, stands at 122 years and 164 days. Everything beyond that is mathematical extrapolation, not observed biology.
The work affects both aging science and future therapeutic strategy, signaling that even the most advanced anti-aging interventions may hit a hard biological limit unless genomic damage can be controlled. But the model’s assumptions about how organs interact and fail introduce uncertainty. Different assumptions about the rate at which somatic mutations accumulate in neurons versus cardiomyocytes, or about the threshold of mutation burden at which cell function begins to degrade, could shift the predicted ceiling in either direction.
The model does not claim humans will live to 190. Instead, it provides a ranking system for aging mechanisms, showing which ones shorten life the most and where interventions might matter most. The 146-to-194-year range generated by multi-organ integration is a theoretical envelope, calculated under assumptions of near-total control over every other aging process – a scenario that does not exist and may never exist.
DNA errors account for roughly half the gap between theoretical immortality and actual human longevity, meaning something else is responsible for the other half. The authors acknowledge this directly and plan to incorporate additional aging hallmarks into subsequent model iterations, building a comprehensive quantitative theory of human aging that accounts for mitochondrial dysfunction, telomere erosion, and epigenetic drift alongside somatic mutations.
What This Means for You
The 2026 Skoltech study, published in npj Aging, does not promise that humans will live to 156 years. It establishes, for the first time using a rigorous mathematical framework, what somatic mutations alone would allow if every other driver of aging were neutralized. The answer – a median lifespan ceiling of 146 to 194 years – is roughly double the current biological maximum observed in any verified human.
For anyone tracking the science of human lifespan extension, the organ-level findings carry the most immediate practical significance. Liver cells, which divide continuously, can theoretically sustain themselves for millennia. Neurons and cardiomyocytes cannot renew themselves, and the somatic mutations building up inside them over decades appear to be the primary biological factor limiting how long any human being can survive. The diseases that fill ICUs and memory care units – heart failure and dementia – are concentrated in precisely those tissues. According to this model, that is the predictable consequence of irreplaceable cells accumulating irreversible genetic damage.
For clinicians, the study delivers a more precise target hierarchy: interventions aimed at protecting the DNA integrity of neurons and cardiac muscle cells should rank above those focused on already self-renewing tissues. Gene therapy, cellular reprogramming, and DNA-repair enhancement in post-mitotic cells are not yet clinically viable – but the Skoltech framework gives researchers a mathematically grounded reason to prioritize them. The next step, as the team notes, is building the full model: one that incorporates every hallmark of aging and calculates, with far greater precision, exactly what it would take to push that ceiling higher.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis, or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.