Mathematical model suggests human lifespan capped at about 156 years due to somatic DNA mutations
Researchers used a multistage model to estimate that, even if all aging processes except somatic mutations were eliminated, the median human lifespan would top out around 156 years, with non-renewing brain and heart cells setting the limit.
A team of scientists has developed a mathematical model that estimates a theoretical ceiling for human longevity at roughly 156 years when every reversible hallmark of aging is removed except somatic mutations, the irreversible DNA errors that accumulate in non-reproductive cells. The model, published in npj Aging, simulates the sequential activation of aging mechanisms and measures the resulting lifespan if all but somatic mutations were cured.
The authors report that the brain and heart, whose cells cannot divide, become the primary bottlenecks, limiting median lifespan to between 146 and 194 years. > "Neurons and cardiomyocytes, which lack the ability to divide, turned out to be the main limiting factors," co-author Evgeniy Efimov said.
Assistant Professor Jordan Weiss of NYU Grossman School of Medicine noted that the model’s tissue-specific findings mirror real-world patterns, adding that dementia and heart failure disproportionately affect organs that cannot regenerate.
The researchers began with a hypothetical “non-aging human” whose mortality risk does not increase with age, yielding a median lifespan of 1,759 years. Re-introducing somatic mutations reduced this to 156 years, indicating that DNA damage in non-renewing tissues accounts for roughly half the gap between theoretical immortality and observed human lifespan.
Pharmacist and regenerative-medicine researcher Egle Pavyde said the study quantifies a long-suspected limitation, while Michael Leone, an assistant professor at NYU, described somatic mutations as a challenging but important target for geroscience, noting that other interventions such as mTOR inhibition or senescent-cell clearance may be more immediately actionable.
The authors plan to extend the model to incorporate additional aging hallmarks, including mitochondrial dysfunction, epigenetic drift, telomere shortening and loss of proteostasis, aiming to create a comprehensive quantitative framework for ranking mechanisms that shorten life and guiding future therapeutic priorities.