Biology of senescent liver peroxisomes: Role in hepatocellular aging and disease

Despite rising interest in the health problems of the elderly, information on senescence-related alterations in essential metabolic pathways and their responses to various chemicals is scarce. Although peroxisomal pathways ar e involved in a multitude of cellular functions, little attention has been given to the potential relationship between senescence of these organelles and the process of aging and disease. Although the prevailing experimental evidence points to a decline in liver peroxisomal enzyme activities and a m uted response to peroxisome-proliferating chemicals in aged animals, it is also evident that aged animals are more susceptible, in comparison to their young counterparts, to the hepatocarcinogenic effects of these chemicals. Furthermore, little is known about extraperoxisomal effects of peroxisome p roliferators in aged animals. This review evaluates published studies on th e impact of aging on basal hepatic peroxisomal metabolism, response to pero xisome proliferators, and changes in signal transduction pathways involved in these processes, with the aim of stimulating research efforts in this im portant area. The potential intricate relationship among senescent peroxiso mes, aged hepatocytes, and health are also discussed.