One can debate aspects of the way in which researchers here model what might happen if all of aging is controlled except random mutational damage to nuclear DNA, but the idea is an interesting one. Will random mutational damage to somatic cells be so much harder to eliminate than other aspects of aging that we should think ahead in this way? In tissues where cells are largely replaced, we might think that stem cell populations can at some point be repaired or replaced, and thus the mutational burden in tissues can be reduced over time via the influx of less damaged somatic cells created by the rejuvenated stem cell population. Most neurons in the central nervous system are long-lived, however, and are never replaced. We would have to postulate some very advanced technology to think that we will be able to address the stochastic mutational burden of vital cells in the brain, that damage different in every cell.
Somatic mutations accumulate with age and can cause cell death, but their quantitative contribution to limiting human lifespan remains unclear. We developed an incremental modeling framework that progressively incorporates factors contributing to aging into a model of population survival dynamics, which we used to estimate lifespan limits if all aging hallmarks were eliminated except somatic mutations.
Our analysis reveals 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 430 years to 169 years. In contrast, proliferating tissues like liver maintain functionality for thousands of years through cellular replacement, effectively neutralizing mutation-driven decline.
Multi-organ integration predicts median lifespans of 134-170 years - approximately twice current human longevity. This substantial yet incomplete reduction indicates that somatic mutations significantly drive aging but cannot alone account for observed mortality, implying comparable contributions from other hallmarks.
Link: https://doi.org/10.1101/2025.11.23.689982
View the full article at FightAging
