Denervation Stimulates Apoptosis But Not Id2 Expression in Hindlimb Muscles of Aged Rats

Abstract

Inhibitors of differentiation (Id) proteins are repressors of myogenic regulatory factors and have been implicated in apoptosis and muscle atrophy during aging. Indeed, we have previously found that Id levels are elevated in muscles from old rodents, possibly as a consequence of loss of alpha-motoneurons during senescence. To determine if Id2 proteins increase after denervation and if this is accompanied by increased apoptosis in aged as compared with adult animals, the gastrocnemius and soleus muscles were denervated in 1 limb of Fischer 344 x Brown Norway rats aged 9 months (adult, n = 12) and 33 months (aged, n = 9), while the contralateral limb served as the intra-animal control. After 14 days, the muscles in each limb were removed. The levels of Id1, Id2, and Id3 mRNA and protein were significantly greater in muscles of old as compared with young adult rats. Denervation, however, did not significantly increase Id1, Id2, and Id3 mRNA in soleus or gastrocnemius muscles from either young or old rats. Also Id2 protein levels were similar in denervated and control muscles from young adult and old rats. In young adult rats only, denervation induced an increase in Id1 and Id3 protein levels in both the soleus (Id1 113%; Id3 900%) and gastrocnemius (Id1 86%; Id3 80%). Denervation induced a significant increase in caspase 8 in both soleus and gastrocnemius muscles from young (101% and 147%, respectively) and old rats (167% and 190%, respectively). Bax protein levels, as estimated by western blots, increased by 726% and 1087% after denervation in the soleus and by 368% and 49% in the gastrocnemius muscles of young and old rats, respectively. The data suggest that the denervation-induced muscle loss was at least partly due to apoptosis as indicated by elevated caspase 8 and Bax levels in denervated muscles. While Id2 may have a role in aging-induced sarcopenia, Id2 does not appear to directly regulate apoptosis during denervation. The elevated Id expression in muscles from aged animals is therefore not a direct consequence of loss of alpha-motoneurons during senescence.

Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

“…† P<0.05 indicates significant difference from aged (26 month) group. n=4 each group It has been suggested that the mechanisms of agerelated apoptosis may differ in fast-and slow-twitch muscle types [21][22][23]. The data of the present study are consistent with this notion.…”

Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

“…This pattern was analogous to that observed for tissue levels of HNE and 3-nitrotyrosine, suggesting that the enhanced oxidative and nitrosative stress might have influenced the mitochondrial content of those proteins (Savory, Rao, Huang, Letada, and Herman 1999;Mishra, Randis, Ashraf, and ivoria-Papadopoulos 2006;Qin, Yan, Patel, Liu, and Dong 2006). However, in contrast to previous studies (Alway et al 2002;Alway et al 2003;Song et al 2006;Chung and Ng 2006), we did not detect an age-related increase in the Bax to Bcl-2 ratio. While this finding may be interpreted as a compensatory action aimed at preventing myonuclei loss, we found a concomitant increase of total mitochondrial content of Bid.…”

Effects of alfacalcidol on circulating cytokines and growth factors in rat skeletal muscle

“…Similar to previous observation in both human [31] and rat muscles [32,33], we observed that the specific tension (maximum tetanic force per muscle per muscle mass or cross-sectional area) was decreased in the muscles from the old animals [13].…”