Aging Aging

Damage to Mitochondria 22117Causes and Consequences of Damageto MitochondriaMorphological AspectsJaime Miquel and Carlo Bertoni-Freddari1. IntroductionIn recent years the role played by mitochondria in cellular aging has becomethe focus of intensive research. The concept that these energy-producing organellesare involved in aging derives from the views of Harman (1) and Gerschman(2) linking senescence to the damaging effects of free radicals, especiallythose released in the mitochondrial respiratory chain.However, most gerontologists held the opinion that, because mitochondriaare self-replicating organelles, they should be able to counteract any age-relatedloss. Our own electron microscopic studies have provided data in contradictionwith that former view. Thus, in our study of Drosophila aging we were the firstto demonstrate that the fixed-postmitotic cells of insects accumulate an agepigment structurally similar to the lipofuscin present in mammalian cells andthat many of the pigment granules derive from degenerating mitochondria (3,4).Further, our investigation of the testis of aged mice showed a striking mitochondrialdegeneration and loss in the fixed-postmitotic Sertoli and Leydigcells, while the mitochondria of the fast-replicating spermatogonia (also presentin that organ) did not show any age-related change. This led us to propose themitochondrial theory of aging (5–7), according to which senescence is linkedto the injurious effects of oxy-radicals on the mitochondrial genome of neuronsand other types of differentiated cells. This extranuclear somatic mutationconcept of aging is supported by the finding that mitochondrial DNA (mtDNA)synthesis takes place at the inner mitochondrial membrane near the sites offormation of highly reactive oxygen radicals and their products such asFrom: Methods in Molecular Medicine, Vol. 38: Aging Methods and ProtocolsEdited by: Y. A. Barnett and C. R. Barnett © Humana Press Inc., Totowa, NJ221