Ajuga turkestanica increases Notch and Wnt signaling in aged skeletal muscle

S T Arthur 1, K A Zwetsloot, M M Lawrence, D C Nieman, M A Lila, M H Grace, R Howden, I D Cooley, J F Tkach, M D Keith, J L Demick, S E Blanton, R S Greiner, A M Bradley, M E Davenport, V Badmaev, R A Shanely

Abstract

Background: The declining myogenic potential of aged skeletal muscle is multifactorial. Insufficient satellite cell activity is one factor in this process. Notch and Wnt signaling are involved in various biological processes including orchestrating satellite cell activity within skeletal muscle. These pathways become dysfunctional during the aging process and may contribute to the poor skeletal muscle competency. Phytoecdysteroids are natural adaptogenic compounds with demonstrated benefit on skeletal muscle.

Aim: To determine the extent to which a phytoecdysteroid enriched extract from Ajuga turkestanica (ATE) affects Notch and Wnt signaling in aged skeletal muscle.

Materials and methods: Male C57BL/6 mice (20 months) were randomly assigned to Control (CT) or ATE treatment groups. Chow was supplemented with either vehicle (CT) or ATE (50 mg/kg/day) for 28 days. Following supplementation, the triceps brachii muscles were harvested and immunohistochemical analyses performed. Components of Notch or Wnt signaling were co-labelled with Pax7, a quiescent satellite cell marker.

Results: ATE supplementation significantly increased the percent of active Notch/Pax7+ nuclei (p = 0.005), Hes1/Pax7+ nuclei (p = 0.038), active B-catenin/Pax7+ nuclei (p = 0.011), and Lef1/Pax7+ nuclei (p = 0.022), compared to CT. ATE supplementation did not change the resting satellite cell number.

Conclusions: ATE supplementation in aged mice increases Notch and Wnt signaling in triceps brachii muscle. If Notch and Wnt benefit skeletal muscle, then phytoecdysteroids may provide a protective effect and maintain the integrity of aged skeletal muscle.