Epigenetic estimates reveal a species-specific extension of lifespan in modern humans

Humans are exceptionally long-lived given their body size, with life expectancy further extended by technological and economic progress. Yet, the biological upper limit of human lifespan remains debated. Here, we explored theoretical upper bound of human lifespan by assessing the commonly used DNA methylation clocks and the methylation profiles from centenarians. Although clock accuracy declines at advanced age, the majority of estimates place the potential human lifespan in the range of 128–202 years. By mapping and comparing orthologous methylation sites in the Altai Neanderthal and Denisovan genomes, we estimate their lifespans at 38.2–64.5 years and 40.0–69.8 years, respectively—approximately two decades longer than fossil-based estimates. These findings highlight a novel application of methylation profiling to probe the biological upper limit of lifespan and suggest that substantially extended longevity is a derived trait unique to the modern human lineage.