Mitochondrial DNA deletions parallel age-linked decline in rat sensory nerve function

In rats, the function of sensory nerves in the hind limb declines significa ntly with age. Normally aging rats and rats treated neonatally with capsaic in were studied here. Quantification of vascular response and substance P i n young (3 months) and old (24 months) rats showed additive effects of age and capsaicin treatment. The levels in dorsal root ganglion of a particular deletion in mitochondrial DNA (mtDNA(4834)) were about 300-fold higher in old compared to young tars. Capsaicin treatment had no significant effect o n mtDNA(4834) abundance. Dorsal root ganglia of old (but not young) rats we re found to contain a spectrum of multiple deletions. The abundance of mtDN A(4834) in dorsal root ganglia from individual rats correlated strongly wit h their decline in vascular function, even where vascular responses were sy stematically depressed due to prior capsaicin treatment. One possibility is that mitochondrial DNA mutations directly lead to functional decline at mi tochondrial and tissue levels. Alternatively, loss of mitochondrial DNA int egrity and physiological decline may be consequences of the same factor, su ch as oxidative stress. (C) 2001 Elsevier Science Inc. All rights reserved.