Spermadine is one of many compounds identified to date that trigger some of the same beneficial stress response mechanisms that are upregulated by calorie restriction. For example, spermadine is known to boost the operation of autophagy, a collection of cellular maintenance processes responsible for recycling damaged structures and unwanted proteins. Keeping the level of damage lower means a lesser a chance of generating further detrimental consequences. The outcome, at least in short-lived species, is a longer healthy life span.
Unfortunately, the strategy of enhancing stress responses produces diminishing returns as species life span increases. The effects on longevity become ever smaller, even while the short term benefits to health tend to look quite similar. Why this is the case is not fully understood, but the data is inarguable. Humans cannot reliably live to see 150 on the basis of calorie restriction, though mice gain as much as a 40% increase to life span as a result of that intervention. Mice engineered to lose growth hormone or growth hormone receptor function live even longer yet, but the human population of Laron syndrome growth hormone receptor loss of function mutants do not appear to live significantly longer than