Among the determinants of the metabolic fiber type, PGC1α was significantly reduced in both OW and ONW compared to YG, while AMPK was down-regulated only in ONW. Surprisingly, atrogenes (MURF1 and atrogin) expression was also significantly reduced compared to YG and this was accompanied by a close to statistically significantly attenuated marker of autophagy, LC3. In all oldest-old both myostatin and IGF-1 expression were attenuated compared to YG, however, in ONW two specific IGF-1 isoforms, IGF-1EA and MGF, demonstrated a further significant decrease compared to OW. We analyzed, by RT-qPCR, the expression of genes relevant for fiber size and type regulation in a biopsy sample from the vastus lateralis. Myonuclear density was increased in muscles of ONW, compared to YG and OW, potentially indicative of an ongoing atrophy process. We confirmed previous results of fiber preservation and, additionally, observed a shift in fiber type, toward slow predominance in OW and fast predominance in ONW. Here, we investigated the mechanisms behind this fiber preservation and the relevance of physical activity, by comparing a group of 6 young healthy controls (YG: 22–28 years) with two groups of oldest-old (81–96 years), one able to walk (OW: n = 6, average 86 years) and one confined to a wheelchair (ONW n = 9, average 88 years). This suggests that, while most fibers are likely lost with their respective motoneurons, the surviving fibers are well preserved. As recently documented by us and others, muscle atrophy and weakness are accompanied by an unexpected preservation of the size and contractile function of skeletal muscle fibers. The oldest-old, in the ninth and tenth decades of their life, represent a population characterized by neuromuscular impairment, which often implies a loss of mobility and independence. 9Institute for Kinesiology Research, Science and Research Center of Koper, Koper, Slovenia.Whalen VA Medical Center, Salt Lake City, UT, United States 8Geriatric Research, Education, and Clinical Center, George E.7Department of Nutrition and Integrative Physiology, The University of Utah, Salt Lake City, UT, United States.6Division of Geriatrics, Department of Internal Medicine, The University of Utah, Salt Lake City, UT, United States.5Monsignor Arrigo Mazzali Foundation, Mantova, Italy.4Department of Biomedical Sciences, University of Padova, Padua, Italy.3Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.2Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
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Fabio Naro 1, Massimo Venturelli 2, Lucia Monaco 3, Luana Toniolo 4, Ettore Muti 5, Chiara Milanese 2, Jia Zhao 6,7,8, Russell S.