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.