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 1759 years to 156 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 146–194 years—approximately twice current human longevity