Age-related changes in adrenergic regulation of contractility and redox status of glycolytic and oxidative skeletal muscles.

Abstract

Aging is associated with skeletal muscle weakness and oxidative stress. Here, we hypothesized that aging may lead to alterations in adrenoceptor (AR)-dependent regulation of muscle contractility. These changes can aggravate muscle contractile dysfunction and correlate with redox disturbances. Glycolytic extensor digitorum longus (EDL) and oxidative soleus muscles from young adult (3 months), middle-aged (12 months), and old (24 months) mice were used. Contractile responses were elicited by electrical stimulation at different frequencies. During the aging process, inotropic effects of adrenaline in both muscles changed in a similar manner. Adrenaline caused a positive inotropic effect in young adult mice, then its action disappeared at middle age, and, finally, adrenaline decreased the contraction force at old age. Fenoterol, a β-AR agonist, exerted a negative inotropic action in EDL and soleus muscles of young adult and middle-aged mice. This effect of fenoterol is partially preserved in soleus (but not EDL) muscles at advanced age. In both muscles, the positive inotropy of adrenaline was blocked by β2-AR antagonist, whereas the fenoterol-mediated suppression of contraction force was inhibited by β3-AR antagonists. Immunofluorescent labeling revealed both β2- and β3-AR-positive signals at the sarcolemma. Accordingly, the age-related shift of balance from positive to negative inotropic action of adrenaline might be partially dependent on the interplay of β2- and β3-adrenergic signaling in the skeletal muscles. Despite the commonalities in the changes in adrenergic regulation of contractions in both muscles, oxidative stress, decline in antioxidant enzyme activities, and ultrastructural disturbances were much more clearly expressed in aged EDL versus soleus muscles.