2. Large Lifespan Gains May be Easier to Obtain in Model Organisms than in Humans

Short-lived species and many lab models often sit farther from maximal protection, so shifting nutrient sensing, growth, or stress responses can produce large relative gains. Long-lived mammals (e.g., humans) and many birds are already highly protected by evolution, meaning the remaining points of improvement are fewer, more distributed, and harder to achieve without tradeoffs. This is why dramatic lifespan extension is common in nematodes and flies and frequent in mice, whereas no intervention has yet shown robust, reproducible extension of maximum human lifespan in controlled settings. On the other hand, we cannot realistically run decades-long, tightly controlled intervention trials in otherwise healthy humans to test effects on maximum lifespan, so the absence of robust lifespan-extension results partly reflects feasibility, not only biology. Within species-level maximal lifespan constraints, translational targets in humans may focus on systems with accelerated aging, thereby maximizing healthspan and mean lifespan.