Age-associated changes in mitochondrial parameters on peripheral human lymphocytes

Among theories of aging, mitochondria are believed to be involved in senesc ence. Alterations of respiratory chain function and accumulation of various mitochondrial DNA mutations have been reported in mammalian postmitotic ti ssues. Because mitochondria have a central role in apoptosis and in adenosi ne triphosphate production, alteration of mitochondria function could contr ibute to immune senescence. We searched for alterations of mitochondrial pa rameters in peripheral lymphocytes with aging. Comparisons of respiratory c hain activities of complex II+III, III, and IV were carried out in two popu lations of healthy volunteers with average ages of 35.3 +/- 6.7 years and 8 0.8 +/- 8.7 years. No difference was observed in complex IV activity betwee n each group, whereas a significant decrease of complex II+III and a nonsig nificant decrease of complex In, activity were observed with aging. Alterat ions in mitochondrial functions can result from mutations in mitochondrial DNA (mtDNA), the most common being the 4977-bp deletion (mtDNA(-4977)). In either group we observed many deletions of mtDNA on peripheral blood lympho cytes by large-fragment polymerase chain reaction. This result suggests tha t alterations of respiratory chain activities observed with aging in lympho cytes could be the result of nuclear DNA dysfunction, with consequences on immune function (reduced responsiveness to antigen). Its possible implicati on on the recent observation of increased apoptosis of CD45RA+RO- T cells w ith aging is discussed. (C) 1999 Elsevier Science Inc. All rights reserved.