Endocrine Abstracts

It is considered that reactive oxygen species (ROS) and free radicals in general, are involved in a variety of physiological and pathological processes including degenerative disease and probably ageing. Age-related accrual of oxidative stress is a balance between ROS-induced generation rates and the activity of antioxidant defence enzymes, tissue antioxidant concentrations, repair processes, chaperone protein activity and molecular and cellular turnover rates. End-point measures of oxidative stress such as tissue lipoperoxidation, oxidative lesions in genomic and mitochondrial DNA and protein carbonyl formation increase with ageing. The accumulation of oxidized protein in neural tissue is associated with identifiable behavioural and functional impairments in short-lived animals. Age-related accumulation of oxidized protein can be partly reversed by spin-trapping compounds and this is associated with the restoration of functional behavioural deficits. Experimental strategies recognised to delay ageing in mammals significantly retard the accumulation of protein carbonyl and lipid peroxidation species.

ROS is generated at many cellular sites as well as during electron transport in the mitochondria, which are considered particularly susceptible to oxidant damage. The generation of ROS is recognised not to be a direct function of metabolic rate, i.e. the generation of superoxide and H₂O₂ by isolated mitochondria from two species of mice, M. musculus (MLSP= 3.5 years) and P. leucopus (MLSP= 8 years) was 48-74% higher for superoxide, and three to five times greater for H₂O₂ in M. musculus, although P. leucopus has the higher metabolic rate. The importance of oxygen free radicals and oxidative stress as a mechanism of ageing still needs to be clarified considering the failure of antioxidant supplementation to significantly extend life span in mammals. Exogenous antioxidants can interfere with cell signalling and ROS may exert its adverse effects with age by inducing subtle changes in redox-sensitive cell signalling, rather than through gross accumulation of oxidative tissue damage.