Contrasting Effects of Age on Muscle Contractility in Male and Female Rats

Abstract

This study aimed to describe changes in forelimb grip strength and ex vivo muscle force production in adult (Ad) and aged (Ag, 75% lifespan) male (M) and female (F) F344/BN hybrid rats. We hypothesized that differences in M vs. F would be explained by muscle mass, but that age differences would persist after normalizing to mass in fast, but not slow muscles. Forelimb grip was expressed in absolute terms (Grip) and relative to body mass (NGrip). Ex vivo forces of the extensor digitorum longus (EDL) and Soleus (Sol) were assessed at 3 stimulation frequencies and 2 pulse durations, and expressed as absolute muscle force (AMF) and muscle quality (MQ; force/anatomical cross‐sectional area). We also assessed sarcoplasmic reticulum (SR) Ca2+ release and reuptake from homogenates of both muscles. Body mass was higher in Ag vs. Ad and M vs. F (both p < 0.001), while EDL and Sol mass were smaller in F vs. M (p < 0.001), with no effect of age. Grip showed no effect of age, but was significantly (p < 0.001) lower in F while NGrip was higher in Ad vs. Ag (p < 0.001) and F vs. M (p < 0.001). EDL AMF exhibited a significant age X sex interaction (p = 0.006) across frequencies, as AMF declined with age in M, but increased in F. EDL MQ showed a similar pattern (p = 0.039), but only at the highest frequency (120Hz). In Sol, M showed a trend (p = 0.078) for higher AMF relative to F. In contrast, MQ was significantly higher in F vs. M (p = 0.025). Differences in SR function did not appear to contribute to these differences as the only significant effect observed was for SR Ca2+ uptake to be reduced in F vs. M in both EDL and Sol (p = 0.046 & 0.050, respectively). These findings indicate that grip and isolated muscle contractility are generally higher in M vs. F when expressed in absolute terms, but lower in M vs. F when expressed as relative measures (normalized to body mass or muscle size). Minimal declines in muscle contractility occurred with age in either muscle tested, consistent with what we have observed previously with in situ testing of the Sol, but other aged fast muscles.