Scientists have proposed that human lifespan may have a fundamental biological limit, even under the most optimistic anti-aging scenarios. According to a new study, random DNA mutations that accumulate throughout life could eventually cause organs to fail, regardless of future advances in medicine.
The research, published in npj Aging, suggests that even if scientists could eliminate all known age-related diseases and other biological hallmarks of aging, the gradual buildup of DNA damage within cells would still place an upper boundary on human longevity.
Modeling the Biological Limits of Lifespan
Researchers at the Skolkovo Institute of Science and Technology in Russia, led by computational biologist Dmitrii Kriukov, developed a mathematical model to investigate how random DNA mutations accumulate throughout life and affect the body’s organs.
The study focused on somatic mutations—genetic changes that occur in cells after conception. Unlike inherited mutations, somatic mutations are acquired over a person’s lifetime, primarily during cell division, and are not passed on to future generations.
Although cells continually repair damaged DNA, the process is not perfect. Small genetic errors gradually accumulate over decades. While many mutations have little or no effect, others can impair cellular function or increase the risk of diseases such as cancer, contributing to the gradual decline of tissues and organs.
To isolate the effects of these mutations, the researchers modeled a theoretical scenario in which all age-related diseases, including cancer, were completely prevented. The only remaining source of biological decline was the continued accumulation of random somatic mutations.
A Theoretical Lifespan of 146 to 194 Years
Under these highly idealized conditions, the simulations produced median lifespans ranging from approximately 146 to 194 years, depending on the assumptions used in the model. This is roughly twice the current global average life expectancy, which is about 73 years.
Although a small number of simulated individuals survived beyond 200 years, none achieved unlimited lifespan. Even in the most favorable scenarios, accumulated DNA mutations eventually caused enough damage for essential organs to lose their ability to function.
The researchers emphasize that these figures are not predictions of future human longevity. Instead, they represent theoretical biological limits under conditions that eliminate every other known cause of aging except mutation accumulation.
Some Organs May Reach Their Limits Sooner
The model also suggests that organs age at different rates because their cells renew at different speeds.
Tissues such as the skin, liver, and intestinal lining regularly replace damaged or aging cells with new ones. This continual renewal may help reduce the long-term impact of accumulated mutations.
In contrast, many cells within the brain and heart survive for decades and are replaced only rarely. Because these cells remain in the body for so long, they continue accumulating DNA mutations over time, making them particularly vulnerable to irreversible damage.
According to the simulations, the eventual failure of these long-lived cells may become one of the strongest biological constraints on maximum human lifespan, even if future medicine successfully treats other aspects of aging.
DNA Mutations Are Only One Part of Aging
The findings also contribute to a long-standing debate about the causes of aging. The somatic mutation theory proposes that the gradual accumulation of DNA mutations is a major driver of biological aging, but this idea remains controversial.
Modern genetic studies have confirmed that somatic mutations steadily increase throughout life. However, many researchers believe aging results from several interacting biological processes rather than DNA mutations alone. These include cellular senescence, chronic inflammation, metabolic dysfunction, and the gradual exhaustion of stem cells.
Because the model predicted theoretical lifespans substantially longer than those currently observed, the researchers argue that additional biological mechanisms must contribute significantly to aging. Their results support the view that no single process fully explains why humans grow old.
Implications for Anti-Aging Research
The researchers suggest that their mathematical framework could help scientists estimate how much individual biological processes contribute to aging. By comparing models that include or exclude specific mechanisms, future studies may better identify which targets offer the greatest potential for extending healthy lifespan.
Such work could guide efforts to protect long-lived neurons and heart cells, improve DNA repair systems, or reduce chronic inflammation, all of which are active areas of aging research.
The study also indicates that even highly ambitious approaches—including senolytic therapies, gene editing, and other rejuvenation technologies—may eventually encounter a biological limit imposed by the gradual accumulation of DNA mutations. While substantial extensions of healthy lifespan may prove possible, the findings suggest that complete biological immortality remains unlikely based on current scientific understanding.
Adding to the Debate on Human Longevity
The research joins a growing body of scientific work examining whether humans have a fixed maximum lifespan. Some demographic studies have suggested an upper limit of approximately 115 to 125 years based on verified longevity records, while others argue that continued medical advances could gradually increase the ages reached by the oldest individuals.
Although the new model does not resolve this debate, it identifies mutation accumulation as one of the most fundamental biological factors that may ultimately limit lifespan.
The authors describe their work as an initial step toward developing a comprehensive, mechanistic theory of aging. They argue that future progress will require integrating findings from genetics, epidemiology, biophysics, and clinical medicine to better understand how the many biological processes involved in aging interact throughout the human lifespan.
