Aging of skeletal muscle is often accompanied by muscle atrophy and it appears that apoptosis plays an important role in this process. The detailed mechanism(s) is not completely understood, however. In this study, we examined expression of the apoptosis regulatory proteins as well as the heat shock proteins, which have been shown to modulate the apoptotic process in certain cell types, in order to more completely elucidate apoptotic signaling in aged skeletal muscle. To more specifically identify alterations that are likely to be the result of aging, we compared 16-month-old middle-aged (MD) and 29-month-old senescent (SE) male Fischer 344 x Brown Norway rats in our study. Our results show that the degree of DNA laddering was higher in SE compared to MD rats. Using total tissue homogenates we examined the level of expression of several apoptosis-related proteins in two categories: mitochondria-associated proteins and caspases. Of the mitochondria-associated proteins, the levels of p53 showed a significant increase in SE compared to MD rats. There was also a significant increase in the expression of Bax, Bcl-2 and Apaf-1 in SE rats over that of MD rats; cytochrome c and AIF levels remained unchanged, however. Regarding the caspases, there were increases in the levels of pro-caspases-12 and -7 and cleaved caspase-9, although the levels of pro- and cleaved caspase-3 as well as cleaved caspase-12 remained unchanged. Furthermore, our results showed significant increases in HSP27, HSP60, and the inducible HSP70. These data show that in rat skeletal muscle increased apoptosis occurs between middle-age and senescence, indicating an aging-related increase in apoptosis in skeletal muscle. The involvement of different apoptotic pathways in the aging process is suggested by the selective alterations in the apoptosis regulatory proteins. The increased expression of the HSPs suggests a relationship between HSPs and the aging-related apoptotic process.

Previous studies have shown that myocytes isolated from sedentary (Sed) rat hearts 3 wk after myocardial infarction (MI) undergo hypertrophy, exhibit altered intracellular Ca(2+) concentration ([Ca(2+)](i)) dynamics and abnormal contraction, and impaired sarcoplasmic reticulum (SR) function manifested as prolonged half-time of [Ca(2+)](i) decline. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca(2+) regulation, the present study examined whether 6-8 wk of high-intensity sprint training (HIST) would restore [Ca(2+)](i) dynamics and SR function in MI myocytes toward normal. In MI rats, HIST ameliorated myocyte hypertrophy as indicated by significant (P

Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had decreased Na+/Ca2+ exchange currents (I Na/Ca; 3 Na+ out:1 Ca2+ in) and sarcoplasmic reticulum (SR)-releasable Ca2+ contents. These defects in Ca2+ regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+ regulation, the present study examined whether 6-8 wk of high-intensity sprint training (HIST) would ameliorate some of the cellular maladaptations observed in post-MI rats with limited exercise activity (Sed). In MI rats, HIST did not affect citrate synthase activities of plantaris muscles but significantly increased the percentage of cardiac alpha-myosin heavy chain (MHC) isoforms (57.2 +/- 1.9 vs. 49.3 +/- 3.5 in MI-HIST vs. MI-Sed, respectively; P < or = 0.05). At the single myocyte level, HIST attenuated cellular hypertrophy observed post-MI, as evidenced by reductions in cell lengths (112 +/- 4 vs. 130 +/- 5 micrograms in MI-HIST vs. MI-Sed, respectively; P < or = 0.005) and cell capacitances (212 +/- 8 vs. 242 +/- 9 pF in MI-HIST vs. MI-Sed, respectively; P < or = 0.015). Reverse I Na/Ca was significantly lower (P < or = 0.0001) in myocytes from MI-Sed rats compared with those from rats that were sham operated and sedentary. HIST significantly increased reverse I Na/Ca (P < or = 0.05) without affecting the amount of Na+/Ca2+ exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca2+ content, as estimated by integrating forward I Na/Ca during caffeine-induced SR Ca2+ release, was also significantly increased (P < or = 0.02) by HIST in MI myocytes. We conclude that the enhanced cardiac output and stroke volume in post-MI rats subjected to HIST are mediated, at least in part, by reversal of cellular maladaptations post-MI.

The present study tests the hypothesis that endurance exercise training (ETr) reverses age-associated alterations in expression of Na+-K+-ATPase subunit isoforms in rat skeletal muscles. Expression of the isoforms was examined in 16-mo-old sedentary middle-aged, 29-mo-old sedentary senescent, and 29-mo-old treadmill exercise-trained senescent Fischer 344 × Brown Norway rats. Levels of the α1-isoform increased with age in red gastrocnemius (GR), white gastrocnemius (GW), and extensor digitorum longus (EDL) muscles, and ETr further increased its levels. Levels of the α2-isoform were unchanged in GR, had a strong trend for a decrease in GW, and decreased significantly in EDL. ETr increased expression of the α2-isoform in all three muscle groups. There was no increase in expression of the β1-isoform in GR, GW, or EDL with age, whereas ETr markedly increased its levels in the muscles. There was a marked decrease with age in expression of the β2-isoform in the muscle groups that was not reversed by ETr. By contrast, β3-isoform levels increased with age in GR and GW, and ETr was able to reverse this increase. Na+-K+-ATPase enzyme activity was unchanged with age in GR and GW but increased in EDL. ETr increased enzyme activity in GR and GW and did not change in EDL. Myosin heavy chain isoforms in the muscle groups did not change significantly with age; ETr caused a general shift toward more oxidative fibers. Thus ETr differentially modifies age-associated alterations in expression of Na+-K+-ATPase subunit isoforms, and a mechanism(s) other than physical inactivity appears to play significant role in some of the age-associated changes.