The Spin-Trap N-tert-α-Phenylbutylnitrone Prolongs the Life Span of the Senescence-Accelerated Mouse

Abstract

Free radicals and oxidative damage have been proposed as underlying factors in aging, in chronic and degenerative diseases of aging and in acute clinical conditions. To test involvement of free-radicals in such processes, spin trapping agents which quench more reactive radicals to produce long-lived stable radical adducts have been used as an experimental strategy. Spin traps protect against oxidatively induced injury in numerous in vitro and in vivo model systems involving different organs. A model system for mammalian aging is afforded by the senescence accelerated mouse (SAM-P8), which exhibits many features characteristic of mammalian aging but with a much shortened lifespan. Daily intraperitoneal injection of the spin trap N-tert-α-phenyl-butylnitrone (PBN) was administered to male or female mice after they reached maturity at 3 months of age. PBN treated animals as compared with control sham injected animals revealed a remarkable extension of the mean life span in both male and female populations. Overall, a 50% mean survival rate was found of 42 weeks for control as compared to 56 weeks for the PBN administered groups. These results show that the spin trap PBN can prolong lifespan and support the free radical theory of aging.