TY - JOUR A1 - Fernando, Raquel A1 - Drescher, Cathleen A1 - Deubel, Stefanie A1 - Jung, Tobias A1 - Ost, Mario A1 - Klaus, Susanne A1 - Grune, Tilman A1 - Castro, Jose Pedro T1 - Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage JF - Experimental gerontology N2 - 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. KW - Proteasomal system KW - Skeletal muscle KW - Fast and slow fibers KW - Polyubiquitination KW - Oxidized proteins KW - Antioxidants KW - Aging KW - Mitochondrial respiration Y1 - 2018 U6 - https://doi.org/10.1016/j.exger.2018.10.018 SN - 0531-5565 SN - 1873-6815 VL - 117 SP - 45 EP - 52 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Franz, Kristina A1 - Ost, Mario A1 - Otten, Lindsey A1 - Herpich, Catrin A1 - Coleman, Verena A1 - Endres, Anne-Sophie A1 - Klaus, Susanne A1 - Müller-Werdan, Ursula A1 - Norman, Kristina T1 - Higher serum levels of fibroblast growth factor 21 in old patients with cachexia JF - Nutrition : the international journal of applied and basic nutritional sciences N2 - Objective: Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on FGF21 in humans are inconsistent and FGF21 has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of FGF21 with cachexia in old patients compared with their healthy counterparts. Methods: Serum FGF21 and its inactivating enzyme fibroblast activation protein (FAP)-cc were measured with enzyme-linked immunoassays. Cachexia was defined as >= 5% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). Results: We included 103 patients with and without cachexia (76.9 +/- 5.2 y of age) and 56 healthy controls (72.9 +/- 5.9 y of age). Cachexia was present in 16.5% of patients. These patients had significantly higher total FGF21 levels than controls (952.1 +/- 821.3 versus 525.2 +/- 560.3 pg/mL; P= 0.012) and the lowest FGF21 levels (293.3 +/- 150.9 pg/mL) were found in the control group (global P < 0.001). Although FAP-alpha did not differ between the three groups (global P = 0.082), bioactive FGF21 was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total ((beta = 649.745 pg/mL; P < 0.001) and bioactive FGF21 (beta = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. Conclusions: Patients with cachexia exhibited the highest FGF21 levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased FGF21 values contribute to the catabolic state. (C) 2018 Elsevier Inc. All rights reserved. KW - Fibroblast growth factor 21 KW - Cachexia KW - Anorexia KW - Aging KW - Biomarker Y1 - 2018 U6 - https://doi.org/10.1016/j.nut.2018.11.004 SN - 0899-9007 SN - 1873-1244 VL - 63-64 SP - 81 EP - 86 PB - Elsevier CY - New York ER -