Advanced glycation end-product accumulation and associated protein modification in type II skeletal muscle with aging.

One mechanism that may influence the quality of skeletal muscle proteins, and explain the age-related decline in contractility, is protein damage. Advanced glycation end-products (AGE) in vivo are useful biomarkers of damage. In this study, comparison of extensor digitorum longus (EDL) muscles from young (8 months), old (33 months), and very old (36 months) Fischer 344 Brown Norway F1 (F344BNF1) hybrid rats shows that muscles from the very old rats have a significantly higher percentage of myofibers that immunolabel intracellularly for AGE-antibody 6D12 compared to the younger age group.

Protein nitration with aging in the rat semimembranosus and soleus muscles.

On the basis of the accelerated age-related effects in type II muscle, we hypothesized that with aging the semimembranosus (type II) muscle would accumulate a greater amount of oxidized proteins compared to proteins in the soleus (type I) muscle. In this study, 3-nitrotyrosine (3-NT) was used as a stable marker of protein oxidative damage. The presence of 3-NT was evaluated in muscles from young adult, old, and very old Fischer 344 rats to provide an indication of the time course of muscle protein oxidative damage.

Myosin and actin expression and oxidation in aging muscle.

While the age-related loss in muscle mass partially explains the decline in strength, other yet undefined mechanisms contribute. This study investigates whether changes in myosin-actin stoichiometry and oxidative modification could help explain the decrement in muscle strength with aging. Protein expression and oxidation were evaluated in myosin and actin isolated from the soleus and semimembranosus muscles from young adult, old, and very old Fischer 344 rats.

Altered proteasome function and subunit composition in aged muscle.

Myofibrillar protein degradation is mediated through the ubiquitin-proteasome pathway. To investigate if altered proteasome activity plays a role in age-related muscle atrophy, we examined muscle size and proteasome function in young and aged F344BN rats. Significant age-related muscle atrophy was confirmed by the 38% decrease in cross-sectional area of type 1 fibers in soleus muscle.

Stimulation of the ICAM-1 gene transcription by the peroxovanadium compound [bpV(Pic)] involves STAT-1 but not NF-kappa B activation in 293 cells.

Vanadate and peroxovanadium derivatives are potent inhibitors of protein tyrosine phosphatases (PTPs) and exhibit insulinomimetic activities in several cell systems. We have found that in 293 and 293T cells, intercellular adhesion molecule-1 (ICAM-1) gene transcription is activated by bpV(Pic), a picolinic acid-stabilized peroxovanadium derivative. To identify the bpV(Pic)-responsive element(s), several deletion and site-specific mutants of the ICAM-1 gene promoter cloned upstream from the firefly luciferase reporter gene were transiently transfected into both cell lines.