Study reveals hidden DNA damage may decide how long humans live

A groundbreaking study has suggested that the gradual accumulation of DNA errors within cells could set a biological ceiling on human lifespan, even if all other factors of aging were eliminated. Researchers from the Skolkovo Institute of Science and Technology developed a mathematical model to explore how the buildup of somatic mutations, genetic changes that occur after birth and are not inherited, might influence longevity. Their findings, published in npg aging, propose that human lifespan could reach approximately 156 years under idealized conditions where other aging mechanisms are absent. This estimate significantly surpasses the current verified human lifespan record held by Jeanne Calment, who lived to be 122 years and 164 days before passing away in 1997. The study begins by acknowledging humanity's long-standing quest to extend life, initially through medical advancements that reduced early mortality and later through scientific efforts to slow biological aging. However, the research highlights that even if scientists succeeded in eliminating most age-related diseases, the body might still encounter inherent limitations embedded in cellular function. Specifically, the focus is on the inevitable accumulation of DNA errors over time, which could eventually impede cellular performance and contribute to aging-related decline. According to the study, somatic mutations arise during daily cellular activities such as division and self-repair. While many of these mutations have negligible effects, others can impair normal cellular function, particularly when they target critical genes necessary for survival. Over decades, the progressive loss of functional cells could begin to impact tissues with limited regenerative capacity. These genetic alterations represent a form of accumulated informational error within the body, distinct from other aging processes that researchers aim to mitigate or reverse. To calculate the potential upper limit of human lifespan, the researchers constructed a mathematical model that simulated the behavior of different cell types, including neurons, heart muscle cells, liver cells, liver precursor cells, and airway cells. The model assessed mutation rates, the likelihood of disruptions to essential genes, and the body’s ability to replace damaged cells. Based on their analysis, the study posits that the median lifespan could range from around 146 to 194 years, with a central estimate of approximately 156 years. This projection assumes that all other major contributors to aging, such as oxidative stress, telomere attrition, and mitochondrial dysfunction, are effectively neutralized. In a hypothetical scenario designed to isolate the impact of mutations, the researchers first eliminated nearly all other aging-related causes of death. Under these conditions, the theoretical maximum lifespan exceeded 1,700 years. However, introducing mutation-induced cell loss dramatically reduced this estimate, illustrating the complex interplay between various biological processes. Aging, the study argues, does not stem from a single cause but rather results from the cumulative effects of cellular, tissue, and organ-level changes. Among the organs identified as key constraints, the brain stands out due to its composition of neurons, which are largely formed early in life and rarely replaced. If harmful mutations disrupted neuronal function, the body would lack the means to restore lost functionality. Similarly, the heart, composed primarily of non-regenerating cardiac muscle cells, faces similar vulnerabilities. These findings suggest that certain tissues may serve as limiting factors in determining the ultimate duration of human life.