Role and potential mechanisms of anabolic resistance in sarcopenia

Abstract

There is pressing need to understand the aging process to better cope with its associated physical and societal costs. The age-related muscle wasting known as sarcopenia is a major contributor to the problems faced by the elderly. By hindering mobility and reducing strength, it greatly diminishes independence and quality of life. In studying the factors that contribute to the development of sarcopenia, the focus is shifting to the study of disordered muscle anabolism. The abnormal response of muscle to previously well-established anabolic stimuli is known as anabolic resistance, and may be a key factor in the development and progression of sarcopenia. Factors such as age, obesity, inflammation, and lipotoxicity contribute to anabolic resistance, and have been studied either directly or indirectly in cell systems and whole animals. Understanding the physiologic and mechanistic basis of anabolic resistance could be the key to formulating new and targeted interventions that would ease the burden currently borne by the world’s aged population.

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes

“…Furthermore, NF-B and STAT3 have the potential to disrupt anabolic activation of muscle protein synthesis (19). For example, anabolic resistance to amino acid and resistance exercise caused by either sarcopenia or sepsis is associated with NF-B activation (23). Muscle contraction-induced mTORC1 signaling is attenuated in severely cachectic Apc Min/ϩ mice, which exhibit chronic activation of muscle STAT3 (50).…”

Yaşlılık ve sağlıklı beslenme

“…Son dönem çalışmalarda; kas protein sentezi ve kas protein yıkımı arasındaki dengenin bozulmasıyla ilişkili olduğu bildirilmektedir. İskelet kası, total kas kitlesinin %40-50'sini oluşturur ve özellikle hareketin oluşturulmasında bazal vücut enerji metabolizması için primer dokudur (22). Ayrıca, yaş ile kas kütlesinin protein içeriğinde azalma olurken, yağ miktarı artar.…”

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“…Es gibt keinen Beleg dafür, dass noch höhere Proteinmengen Vorteile bringen, aber ein Argument dafür wäre, dass bei Tumorpatienten vielfach eine "anabole Resistenz" vorliegt. Darunter wird verstanden, dass die Schwelle zur Stimulation der Proteinsynthese durch Aminosäuren gegenüber der Norm relevant erhöht ist ("anabolic resistance") [108]. Diese Schwelle wird durch ein hohes Protein-oder Aminosäurenangebot v. a. dann überschritten, wenn gleichzeitig eine Hyperinsulinämie besteht, wie man sie durch Kohlenhydrate herbeiführen kann [109].…”

“…Kommentar: Patienten mit einem malignen Tumor weisen oft eine "anabole Resistenz" ihrer Muskulatur auf [108,169]. Dies bedeutet, dass zur Induktion einer Proteinanabolie die Zufuhr einer größeren Aminosäurenmenge erforderlich ist als bei metabolisch gesunden Personen.…”