Motor neuron targeting of IGF-1 attenuates age-related external Ca2+-dependent skeletal muscle contraction in senescent mice.
A population of fast muscle fibers from aging mice is dependent on external Ca(2+) to maintain tetanic force during repeated contractions. We hypothesized that age-related denervation in muscle fibers plays a role in initiating this contractile deficit, and that prevention of denervation by IGF-1 overexpression would prevent external Ca(2+)-dependent contraction in aging mice. IGF-1 overexpression in skeletal muscle prevents age-related denervation, and prevented external Ca(2+)-dependent contraction in this work. To determine if the effects of IGF-1 overexpression are on muscle or nerve, aging mice were injected with a tetanus toxin fragment-C (TTC) fusion protein that targets IGF-1 to spinal cord motor neurons. This treatment prevented external Ca(2+)-dependent contraction. We also show evidence that injections of the IGF-1-TTC fusion protein prevent age-related alterations to the nerve terminals at the neuromuscular junctions. We conclude that the slow age-related denervation of fast muscle fibers underlies dependence on external Ca(2+) to maintain tetanic force in a population of muscle fibers from senescent mice.
Payne
Anthony M
AM
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Messi
María Laura
ML
Zheng
Zhenlin
Z
Delbono
Osvaldo
O
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000032:analysis; D006614:Hindlimb; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013744:Tetanus Toxin / Q000008:administration & dosage
D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D009466:Neuromuscular Blocking Agents; D010446:Peptide Fragments; D013744:Tetanus Toxin; C040635:tetanus toxin fragment C; D007334:Insulin-Like Growth Factor I; D002118:Calcium