@article{FernandoDrescherNowotnyetal.2018, author = {Fernando, Raquel and Drescher, Cathleen and Nowotny, Kerstin and Grune, Tilman and Castro, Jose Pedro}, title = {Impaired proteostasis during skeletal muscle aging}, series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, volume = {132}, journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, publisher = {Elsevier}, address = {New York}, issn = {0891-5849}, doi = {10.1016/j.freeradbiomed.2018.08.037}, pages = {58 -- 66}, year = {2018}, abstract = {Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation. Since the UPS and ALS are the two most important pathways for the removal of misfolded and aggregated proteins and also of damaged organelles, we provide here an overview on the current knowledge regarding the connection between the loss of proteostasis and skeletal muscle functional impairment and also how redox regulation can play a role during aging. Therefore, this review serves for a better understanding of skeletal muscle aging in regard to the loss of proteostasis and how redox regulation can impact its function and maintenance.}, language = {en} } @article{FernandoDrescherDeubeletal.2018, author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Jung, Tobias and Ost, Mario and Klaus, Susanne and Grune, Tilman and Castro, Jose Pedro}, title = {Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage}, series = {Experimental gerontology}, volume = {117}, journal = {Experimental gerontology}, publisher = {Elsevier}, address = {Oxford}, issn = {0531-5565}, doi = {10.1016/j.exger.2018.10.018}, pages = {45 -- 52}, year = {2018}, abstract = {The skeletal muscle is a crucial tissue for maintaining whole body homeostasis. Aging seems to have a disruptive effect on skeletal muscle homeostasis including proteostasis. However, how aging specifically impacts slow and fast twitch fiber types remains elusive. Muscle proteostasis is largely maintained by the proteasomal system. Here we characterized the proteasomal system in two different fiber types, using a non-sarcopenic aging model. By analyzing the proteasomal activity and amount, as well as the polyubiquitinated proteins and the level of protein oxidation in Musculus soleus (Sol) and Musculus extensor digitorum longus (EDL), we found that the slow twitch Sol muscle shows an overall higher respiratory and proteasomal activity in young and old animals. However, especially during aging the fast twitch EDL muscle reduces protein oxidation by an increase of antioxidant capacity. Thus, under adaptive non-sarcopenic conditions, the two fibers types seem to have different strategies to avoid age-related changes.}, language = {en} }