Mitochondrial DNA deletions parallel age-linked decline in rat sensory nerve function.
In rats, the function of sensory nerves in the hind limb declines significantly with age. Normally aging rats and rats treated neonatally with capsaicin were studied here. Quantification of vascular response and substance P in 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 rats. Capsaicin treatment had no significant effect on mtDNA(4834) abundance. Dorsal root ganglia of old (but not young) rats were found to contain a spectrum of multiple deletions. The abundance of mtDNA(4834) in dorsal root ganglia from individual rats correlated strongly with their decline in vascular function, even where vascular responses were systematically depressed due to prior capsaicin treatment. One possibility is that mitochondrial DNA mutations directly lead to functional decline at mitochondrial and tissue levels. Alternatively, loss of mitochondrial DNA integrity and physiological decline may be consequences of the same factor, such as oxidative stress.
Nagley
P
P
Department of Biochemistry and Molecular Biology, Monash University, 3800, Clayton, Victoria, Australia. phillip.nagley@med.monash.edu.au
Zhang
C
C
Lim
M L
ML
Merhi
M
M
Needham
B E
BE
Khalil
Z
Z
D000375:Aging / Q000502:physiology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology*; D017353:Gene Deletion; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012584:Sciatic Nerve / Q000166:cytology / Q000503:physiopathology; D013373:Substance P / Q000032:analysis; D014665:Vasodilator Agents / Q000494:pharmacology
D004272:DNA, Mitochondrial; D014665:Vasodilator Agents; D009599:Nitroprusside; D013373:Substance P; D002211:Capsaicin