Somatic Cell Mutations May Limit Human Lifespan to 156 Years, Study Finds

Even if science conquers cancer, chronic diseases, and the physical decline of aging, human lifespan may still be capped at 156 years. This limit is imposed not by aging itself, but by the accumulation of somatic cell mutations.

These mutations occur when cells divide or repair DNA damage. Unlike genetic mutations passed to offspring, somatic mutations build up over a lifetime. They gradually damage cells and impair function, contributing to age-related diseases. Tissues with limited cell regeneration, such as the heart muscle and nerve cells, are particularly vulnerable, as damaged cells cannot be easily replaced.

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This study's most important finding is that the differences between tissues are very large. Nerve cells and heart muscle cells, which have no ability to divide, emerged as the biggest factors limiting human lifespan.

A joint study by Russia's Skoltech Institute and the Artificial Intelligence Research Institute (AIRI) used a multi-stage mathematical model to calculate the maximum lifespan under these conditions. They first modeled a "non-aging human" with no increased mortality risk, which theoretically lived until 1759. However, when the impact of somatic mutations was factored in, this theoretical lifespan plummeted to 156 years.

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This study shows that while somatic cell mutations contribute significantly to aging, they alone cannot explain the actual human mortality risk. This implies that other aging mechanisms like the collapse of protein homeostasis, mitochondrial dysfunction, and epigenetic changes also contribute to lifespan limitation at a similar level.

The researchers found significant variation between different tissues. "The most important finding of this study is that the differences between tissues are very large," said Evgeny Efimov, lead author and researcher at Skoltech's Center for Biomedicine. "Nerve cells and heart muscle cells, which have no ability to divide, emerged as the biggest factors limiting human lifespan."

Conversely, highly regenerative tissues like the liver can largely offset the negative effects of mutations, maintaining function for thousands of years. This explains why diseases like dementia and heart failure, linked to damage in limited-regeneration tissues, are prevalent in old age. The study's findings provide a quantitative basis for understanding which aging mechanisms to prioritize for future research and treatment.

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We are not just saying that mutations are harmful, but we have calculated numerically how much they shorten lifespan and can directly compare it with other aging processes. This study is significant for understanding which aging mechanisms should receive the most attention and research resources.