Age-related structural and functional changes of brain mitochondria

Normal ageing is associated with a gradual decline in the capacity of vario us cell types, including neurones, to respond to metabolic stress and retur n to the resting state. An important factor in the decrease of this 'homeos tatic reserve' is the gradual, age-dependent impairment of mitochondrial fu nction. In this article we review some of the major structural and function al changes in mitochondria associated with ageing. Apart from the increased mutations in mitochondrial DNA and the evidence for increased oxidative st ress with ageing, we also discuss, in some detail, the importance of the mi tochondrial membrane structure and composition (in particular lipid composi tion) for mitochondrial function in general and during ageing. Although some of the neurodegenerative diseases are also associated with so me degree of mitochondrial dysfunction, it is not yet clear if these change s are due to the underlining process of normal, physiological ageing or due to the specific pathophysiologic agents responsible for the neurodegenerat ive processes. Furthermore, we are proposing that there are important diffe rences between normal ageing and neurodegeneration. (C) 2000 Harcourt Publi shers Ltd.